Ischemia–reperfusion

The present study was undertaken to evaluate the cardioprotective potential of Curcuma longa (Turmeric) in the ischemia-reperfusion (I/R) model of myocardial infarction (MI). Wistar rats were divided into three groups and received saline orally (sham, control I/R group) and Curcuma longa 100 mg/kg (CL-100 group) respectively for one month. On the 31st day, rats of the control I/R and Cl treated groups were subjected to 45 min of occlusion of the LAD coronary artery and were thereafter reperfused for 1 h. I/R resulted in significant cardiac necrosis, depression in left ventricular function, decline in antioxidant status and elevation in lipid perodixation in the control I/R group as compared to sham control. Myocardial infarction produced after I/R was significantly reduced in the Cl treated group. Cl treatment resulted in restoration of the myocardial antioxidant status and altered hemodynamic parameters as compared to control I/R. Furthermore, I/R-induced lipid peroxidation was significantly inhibited by Cl treatment. The beneficial cardioprotective effects also translated into the functional recovery of the heart. Cardioprotective effect of Cl likely results from the suppression of oxidative stress and correlates with the improved ventricular function. Histopathological examination further confirmed the protective effects of Cl on the heart. D

Background and Purpose-We sought to investigate the impact of hyperglycemia before reperfusion on long-term outcome in patients treated with intravenous tissue plasminogen activator (tPA). Methods-Of 268 consecutive patients with a nonlacunar middle cerebral artery (MCA) stroke evaluated at Ͻ3 hours after onset, 73 (27.2%) received intravenous tPA. Serum glucose was determined at baseline before tPA administration. Hyperglycemia was defined as a glucose level Ͼ140 mg/dL. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and 24 hours. Transcranial Doppler monitoring of recanalization and reocclusion was conducted during the first 24 hours. Total infarct volume was measured on CT at day 5 to 7. Modified Rankin Scale was used to assess outcome at 3 months.

The aim of this study was to determine the effects of a synthetic serine protease inhibitor, gabexate mesilate (GM), in rats with ischemia-reperfusion (I-R) damage due to unilateral testicular torsion. Thirty male Sprague-Dawley rats were separated into three groups, each containing ten rats. A sham operation was performed in group 1 (control). In group 2 (I-R/untreated), 1 h detorsion of the testis was performed after 6 h of unilateral testicular torsion. In group 3 (I-R/GM), after performing the same surgical procedures as in group II, gabexate mesilate was given intravenously. In all experimental rats, ipsilateral orchiectomies were performed for histological examination and measuring the tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). MDA values and the testicular injury score decreased and SOD, CAT and GSH-Px values increased in the GM-treated group compared to the I-R/untreated group. The Tc-99m pertechnetate uptake ratio and the perfusion index were significantly decreased in the group 2 compared to the group 1 and 3 rats. In group 3, these values were significantly increased compared to group 2. Most of the specimens in the GM-treated group showed grade-I testicular injury. However, the injuries in the I-R/untreated rats varied between grade-III and grade-IV. The results of this study show that GM may play a role in reducing the injury caused by I-R.

Purpose: The improvement of the ischaemic tolerance of myocutaneous flaps is of clinical importance and hence the subject of numerous investigations. Methods: In an attempt to increase the ischaemic tolerance, 20 myocutaneous flaps (rectus abdominis muscle) in pigs were elevated and perfused with various, established solutions prior to the onset of ischaemia. The flaps were elevated, utilizing the superior epigastric vessels as the pedicle. Ten flaps were flushed with the University of Wisconsin solution, five with the Euro-Collins solution and the last five with a Ringer-Lactate solution, prior to the 6 h long, normothermic ischaemia. On the day of operation, the first, third, fifth, seventh and tenth postoperative day clincical examinations and thermography were performed as well as biopsies. Additionally, on the tenth postoperative day, the rate of necrosis was determined morphometrically as the average of three measurements. Results: Ten days after surgery, the flaps pretreated with the University of Wisconsin solution displayed a vital surface area of 89%, the Euro-Collins solution 23% and the Ringer-Lactate solution 14%. Histologically, muscle tissue proved to be more susceptible to ischaemia than skin. Conclusion: Regarding the rectus abdominis flap in a pig model, the University of Wisconsin solution proved superior in the prevention of ischaemic injury compared with the Euro-Collins solution and Ringer Lactate. In accordance with the literature, muscle tissue proved to be more susceptible to ischaemia than skin in our study. Ó 2008 European Association for Cranio-Maxillofacial Surgery

A close correlation exists between ischemia/reperfusion (I/R)-induced insult and the release of free radicals. Lecithin is a polyunsaturated phosphatidylcholine that corresponds to the phosphatidylcholine molecule. Phosphatidylcholines are high-energy functional and structural elements of all biologic membranes. ␣-Tocopherol is the major lipidsoluble chain-breaking antioxidant in the body tissues and effectively protects against neuronal damage. Therefore, we studied the effect of lecithin (300 mg/kg, p.o., 14 days) and ␣-tocopherol (200 mg/kg, p.o., 14 days), alone or in combination, on the brain redox state during I/R. Adult male Wistar rats were subjected to global ischemia by the occlusion of the two carotid arteries 24 h after the last dose of drug administration. Reperfusion was carried out 1 h after induction of ischemia and lasted for another hour. Brain lipid peroxides (MDA) and glutathione (GSH) contents, as well as superoxide dismutase (SOD) and catalase (CAT) activities were assessed. The results showed that I/R elevated brain lipid peroxides content which was accompanied by a reduction in both antioxidant enzyme activities, however, brain GSH level remained unaltered. Lecithin, ␣-tocopherol and their combination restored MDA content, as well as CAT activity with a slight tendency to normalize SOD activity. We conclude that lecithin has a possible neuroprotective effect partly through its antioxidant action which is comparable to that of ␣-tocopherol. C

The neocortex and the hippocampus were examined for lipid peroxidation products and ultrastructural alterations by fluorescence and electron microscopy, respectively, in rats subjected to 10 min of cardiac arrest or 10 min cardiac arrest and either 90 or 360 min reperfusion. Lipid peroxidation products were observed after 90 min reperfusion in the perikarya and proximal dendrites of neocortical pyramidal neurons and in the hippocampal hilar cells and CA 1, region; the fluorescence was most intense at the base of the apical dendrite, the region of the Golgi apparatus. After 90 min of reperfusion, the CA 1, showed considerable stretches of rough endoplasmic reticulum devoid of ribosomes and the Golgi cisternae were shorter and widely dilated. The neocortex showed similar endoplasmic reticulum changes, but no significant alterations to the Golgi were noted. In addition there were areas where strings of ribosomes appear to be detaching from the endoplasmic reticulum. After 360 min reperfusion in both the neocortex and the hippocampus, the damage appeared more severe. The Golgi was fragmented into vacuoles, membranous whorls had appeared, and dense aggregates of smooth vesicles were seen coalescing with each other and the vacuoles. These observations suggest that early Golgi involvement is a more important marker of lethal injury than ribosome release from the endoplasmic reticulum. The areas of disturbed Golgi ultrastructure correspond to those areas that show evidence of lipid peroxidation and imply that lipid peroxidation may be causally related to the disturbance in Golgi ultrastructure.

Ozone has recently been subjected to criticism and emphasis in relation to clinical efficacy and toxicity, respectively. Without a doubt, ozone, in common with oxygen itself, is one of the most potent oxidants. Ozone is considered one of the major pollutants in urban areas. Nevertheless, increasingly widespread use lately has highlighted the potential benefits as a therapeutic agent when used according to well-defined and safe protocols. Basic studies conducted following rigorous scientific and ethical criteria have been proposed for scientific discussion. This paper concerns original data on an in vivo model of Parkinson's disease and published data on the effect of low ozone doses with any risk of toxicity excluded with the concentrations commonly used in medical applications. Ó 2008 IMSS. Published by Elsevier Inc.

Verapamil hydrochloride (VCL) is a drug with narrow therapeutic index commonly used in the treatment of mild or moderate systemic arterial hypertension and myocardial ischemia. We have performed pharmaceutical equivalence and comparative dissolution profile studies between reference (R) and several generic (G) medications comprising immediate release coated tablets of VCL (80mg). The analyses were carried out according to the general methods and monograph provided by the Brazilian Pharmacopoeia. The generic medications G1, G2, G3 and G4 were pharmaceutical equivalents to the R, as they were approved in tests of average weight, hardness, friability, disintegration, drug content and uniformity of unit dose. The R, G1, G3 and G4 were all approved at the stage 1 of the dissolution test, while G2 was approved at stage 2. However, none of the G presented dissolution profile similar to the R (18.36 ≤ F2 ≤ 45.15), which may indirectly impair their therapeutical efficacy. Data arising from this study reinforce the necessity of more commitment from the companies producing generic medications in Brazil with the Good Manufacturing Practices and quality of such products, aiming at the promotion of health and overall wellness.

The isolated perfused mammalian heart preparation was established in 1897 by Oscar Langendorff. The method was developed on the basis of the isolated perfused frog heart established by Elias Cyon at the Carl Ludwig Institute of Physiology in Leipzig, Germany in 1866. Observations made using both methods at the end of the 19th and at the beginning of the 20th century led to important discoveries, forming the basis for our understanding of heart physiology. This included the role of temperature, oxygen and calcium ions for heart contractile function, the origin of cardiac electrical activity in the atrium, the negative chronotropic effect of vagus stimulation and the chemical transmission of impulses in the vagus nerve by acetylcholine. Langendorff himself demonstrated that the heart receives its nutrients and oxygen from blood via the coronary arteries and that cardiac mechanical function is reflected by changes in the coronary circulation.The method underwent many modifications but its general principle remains the same today. Blood, or more commonly crystalloid perfusates, are delivered into the heart through a cannula inserted in the ascending aorta, either at constant pressure or constant flow. Retrograde flow in the aorta closes the leaflets of the aortic valve and as a consequence, the entire perfusate enters the coronary arteries via the ostia at the aortic root. After passing through the coronary circulation the perfusate drains into the right atrium via the coronary sinus.The simplicity of the isolated mammalian heart preparation, the broad spectrum of measurements which can be done using this method, its high reproducibility and relatively low cost make it a very useful tool in modern cardiovascular and pharmacological research, in spite of a few shortcomings. In the last decade the method has brought many important advances in many areas including ischemia–reperfusion injury, cell-based therapy and donor heart preservation for transplant.

Contraportada "Cada uno de nosotros tenemos la responsabilidad de actuar como si todos nuestros pensamientos, palabras y actos tuvieran una real importancia, porque, en realidad la tienen. Nuestras vidas tienen tanto un propósito como un significado." Para el Dalai Lama, el sentido común conduce a la felcidad. En su opinión, los seres humanos somos mejores de lo qque pensamos y podemos ayudar a los demás a desarrollar su bondad. Las leyes de la vida ofrece orientación moral a partir de la espiritualidad la compasión como modelos de la conducta humana. En sus páginas, el Dalai Lama explica cómo purificar el alma, el cuerpo y el espíritu, mientras muestra el camino de la liberación. Para ello, trata conceptos como iray emoción, dar y recibir, paz mundial, felicidad, karma y mente, muerte, estadio intermedio, renacimiento o refugio interior. El Dalai Lama Tenzin Gyatso es un excepcional guía espiritual que habla con humildad, calidez y sentido del humor sobre su pensamiento. Sus palabas invitan a la responsabilidad y al desarrollo de la espiritualidad en todas las facetas de la vida. las personas, independientemente de sus diferencias en filosofía y doctrina. Cada tradición religiosa tiene su propio mensaje maravilloso que transmitir. Por ejemplo, desde el punto de vista del budismo, el concepto de un creador es ilógico; debido a la manera en que el budismo analiza la causalidad, resulta un concepto difícil de comprender para los budistas. No obstante, no cabe ahora profundizar en cuestiones filosóficas. El punto importante aquí es que para las personas que siguen enseñanzas en las que la creencia básica reside en un creador, este enfoque resulta muy eficaz. Según esas tradiciones, el ser humano es creado por Dios. Además, por lo que recientemente he aprendido de mis amigos cristianos, no aceptan la teoría del renacimiento, por lo cual tampoco aceptan las vidas pasadas o futuras. Aceptan solamente esta vida. Sin embargo, sostienen que esta misma vida está creada por Dios, por el creador, y esta idea genera en ellos un sentimiento de intimidad con él. Su enseñanza más importante es que, dado que nosotros estamos aquí por voluntad de Dios, nuestro futuro depende del creador, y debido a que éste está considerado como sagrado y supremo, nosotros debemos amarlo. Lo que se observa de esta enseñanza es que nosotros deberíamos amar a nuestros semejantes, los seres humanos; éste es el mensaje esencial. El razonamiento es que si nosotros amamos a Dios, debemos amar a nuestros semejantes, los seres humanos, porque ellos, como nosotros, fueron creados por aquél. Su futuro, así como el nuestro, depende del creador; así pues, su situación es como la nuestra. En consecuencia, resultaría cuestionable la fe de las personas que dicen: «Amad a Dios», pero que no muestran un amor sincero hacia sus iguales, los humanos. La persona que cree en Dios y en el amor hacia él debe manifestar la sinceridad de su amor a través del amor dirigido hacia sus semejantes. Este tipo de enfoque es muy poderoso, ¿no os parece? Si examinamos de esta manera cada religión desde diferentes ángulos, no simplemente a partir de nuestra propia postura filosófica, sino teniendo en cuenta diferentes puntos de vista, no cabe duda de que todas las principales religiones tienen el potencial de hacer mejor al ser humano. Esto es evidente: un contacto estrecho con personas de otras creencias hace posible desarrollar una actitud mental amplia y respeto mutuo con relación a otras religiones. El acercamiento a diferentes creencias me ayuda a aprender nuevas ideas, nuevas prácticas, y nuevos métodos o técnicas que yo puedo incorporar en mi propia práctica. De forma similar, algunos de mis hermanos y hermanas cristianos han adoptado ciertos métodos budistas como, por ejemplo, la práctica de la concentración mental en un solo punto, así como técnicas que ayudan a desarrollar la tolerancia, la compasión y el amor. Resulta de gran beneficio que practicantes de diferentes religiones se reúnan para este tipo de intercambios. Además de desarrollar la armonía entre ellos, también pueden obtenerse otros resultados benéficos. Los políticos y los líderes nacionales hablan con frecuencia de la «convivencia» y el «acercamiento». ¿Por qué no puede ser así también entre las personas religiosas? Creo que ha llegado la hora. En Asís, en 1987, por ejemplo, líderes y representantes de diferentes religiones mundiales se reunieron para orar juntos, aunque no estoy seguro de que la palabra «oración» sea el término adecuado para describir de forma exacta la práctica de todas estas religiones. En cualquier caso, lo importante es que representantes de distintas religiones se reúnan en un mismo lugar y recen, cada uno de acuerdo con su propia fe. Esto ya está sucediendo y, en mi opinión, algo muy positivo se está generando. No obstante, todavía necesitamos poner más esfuerzo en desarrollar la armonía y la proximidad entre las diferentes regiones del mundo, ya que sin tal esfuerzo continuaremos experimentando los numerosos problemas que dividen a la humanidad. Si la religión fuera el único remedio para disminuir el conflicto humano y si este mismo remedio se convirtiera en una fuente más de conflicto, sería algo desastroso. En la actualidad, así como en el pasado, surgen conflictos en nombre de la religión debido a diferencias religiosas, y en mi opinión esto es muy, muy triste. Pero como ya he mencionado anteriormente, si pensamos con una mente más amplia y profunda, nos daremos cuenta de que la situación en el pasado era totalmente distinta a la de hoy. Ya no vivimos de una manera aislada sino interdependiente. Por tanto, en la actualidad es muy importante darse cuenta de que una relación estrecha entre las diferentes religiones es algo fundamental; sólo así los diferentes grupos religiosos tendrán la posibilidad de trabajar juntos de forma más íntima y hacer un esfuerzo común en beneficio de toda la humanidad. Sinceridad y fe en la práctica religiosa por un lado, y tolerancia religiosa y cooperación por el otro, comprenden el primer nivel del valor de la práctica espiritual para la humanidad.

Desde hace varias décadas, en las unidades de cuidados intensivos se ha mantenido la creencia que la instauración de la nutrición enteral está contraindicada absolutamente en el paciente crítico hemodinámicamente inestable. Lo anterior se cree que es debido a la gran entrega de nutrimentos en el lumen intestinal cuando es iniciada la alimentación en estos pacientes, lo cual puede incrementar la demanda de oxígeno mucho más de lo que el cuerpo la puede satisfacer, potencialmente conduciendo a la isquemia intestinal. El objetivo de este manuscrito es realizar una revisión crítica de la literatura para elucidar cada vez un poco más el camino sobre este tema de debate y proporcionar una idea más clara al profesional. Integrando la fisiopatología de la inestabilidad hemodinámica, isquemia intestinal, las propuestas de abordaje
nutricional para la práctica clínica principalmente de sociedades internacionales reconocidas en el
área, así como el abordaje de ciertos autores. Enfocándonos generalizadamente en pacientes con terapia
vasopresora y con presencia de inestabilidad hemodinámica sin enfatizar en la causa, siendo totalmente
imparciales en el desarrollo del tema, es decir, exponiendo las ventajas y desventajas de la instauración
del soporte nutricional enteral en esta población, resumiendo toda la evidencia actual disponible.

Melatonin is a natural occurring compound with well-known antioxidant properties. In the last decade a new effect of melatonin on mitochondrial homeostasis has been discovered and, although the exact molecular mechanism for this effect remains unknown, it may explain, at least in part, the protective properties found for the indoleamine in degenerative conditions such as aging as well as Parkinson's disease, Alzheimer's disease, epilepsy, sepsis and other injuries such as ischemia-reperfusion. A common feature in these diseases is the existence of mitochondrial damage due to oxidative stress, which may lead to a decrease in the activities of mitochondrial complexes and ATP production, and, as a consequence, a further increase in free radical generation. A vicious cycle thus results under these conditions of oxidative stress with the final consequence being cell death by necrosis or apoptosis. Melatonin is able of directly scavenging a variety of toxic oxygen and nitrogen-based reactants, stimulates antioxidative enzymes, increases the efficiency of the electron transport chain thereby limiting electron leakage and free radical generation, and promotes ATP synthesis. Via these actions, melatonin preserves the integrity of the mitochondria and helps to maintain cell functions and survival. D . Synergistic effects of melatonin and deprenyl against MPTP-induced mitochondrial damage and DA depletion. Neurobiology of Aging 24 (3), 491 -500. Kilanczyk, E., Bryszewska, M., 2003. The effect of melatonin on antioxidant enzymes in human diabetic skin fibroblasts. . Modification of nitric oxide synthase activity and neuronal response in rat striatum by melatonin and kynurenine derivatives. . Structure-related inhibition of calmodulin-dependent neuronal nitric-oxide synthase activity by melatonin and synthetic kynurenines. Molecular Pharmacology 58 , 967 -975. Leist, M., Volbracht, C., Fava, E., Nicotera, P., 1998. 1-Methyl-4-phenylpyridinium induces autocrine excitotoxicity, protease activation, and neuronal apoptosis. Molecular Pharmacology 54 (5), 789 -801.

Significance: Mitochondria are dynamic organelles capable of changing their shape and distribution by undergoing either fission or fusion. Changes in mitochondrial dynamics, which is under the control of specific mitochondrial fission and fusion proteins, have been implicated in cell division, embryonic development, apoptosis, autophagy, and metabolism. Although the machinery for modulating mitochondrial dynamics is present in the cardiovascular system, its function there has only recently been investigated. In this article, we review the emerging role of mitochondrial dynamics in cardiovascular health and disease. Recent Advances: Changes in mitochondrial dynamics have been implicated in vascular smooth cell proliferation, cardiac development and differentiation, cardiomyocyte hypertrophy, myocardial ischemia-reperfusion injury, cardioprotection, and heart failure. Critical Issues: Many of the experimental studies investigating mitochondrial dynamics in the cardiovascular system have been confined to cardiac cell lines, vascular cells, or neonatal cardiomyocytes, in which mitochondria are distributed throughout the cytoplasm and are free to move. However, in the adult heart where mitochondrial movements are restricted by their tightly-packed distribution along myofibrils or beneath the subsarcolemma, the relevance of mitochondrial dynamics is less obvious. The investigation of transgenic mice deficient in cardiac mitochondrial fission or fusion proteins should help elucidate the role of mitochondrial dynamics in the adult heart. Future Directions: Investigating the role of mitochondrial dynamics in cardiovascular health and disease should result in the identification of novel therapeutic targets for treating patients with cardiovascular disease, the leading cause of death and disability globally. Antioxid. Redox Signal. 19, 400-414.

Background and Purpose-We aimed to delineate prognostic variables in Israeli patients with anterior circulation strokes treated with endovascular multi-modal reperfusion therapy (MMRT). Methods-Clinical and radiological data from consecutive tpa-ineligible stroke patients with large anterior circulation infarcts involving either the entire internal carotid artery or the proximal middle cerebral artery territory were analyzed. Stroke subtypes were categorized according to TOAST criteria. Neurological deficits were assessed with the NIH stroke scale (NIHSS), and vessel recanalization was determined using the thrombolysis in myocardial infarction (TIMI) scale at the end of MRRT. Good outcome was defined as a modified Rankin score (mRS) Յ2.

In contrast to many years of important research and clinical attention to the pathological effects of alcohol (ethanol) abuse, the past several decades have seen the publication of a number of peer-reviewed studies indicating the beneficial effects of light-moderate, nonbinge consumption of varied alcoholic beverages, as well as experimental demonstrations that moderate alcohol exposure can initiate typically cytoprotective mechanisms. A considerable body of epidemiology associates moderate alcohol consumption with significantly reduced risks of coronary heart disease and, albeit currently a less robust relationship, cerebrovascular (ischemic) stroke. Experimental studies with experimental rodent models and cultures (cardiac myocytes, endothelial cells) indicate that moderate alcohol exposure can promote anti-inflammatory processes involving adenosine receptors, protein kinase C (PKC), nitric oxide synthase, heat shock proteins, and others which could underlie cardioprotection. Also, brain functional comparisons between older moderate alcohol consumers and nondrinkers have received more recent epidemiological study. In over half of nearly 45 reports since the early 1990s, significantly reduced risks of cognitive loss or dementia in moderate, nonbinge consumers of alcohol (wine, beer, liquor) have been observed, whereas increased risk has been seen only in a few studies. Physiological explanations for the apparent CNS benefits of moderate consumption have invoked alcohol’s cardiovascular and/or hematological effects, but there is also experimental evidence that moderate alcohol levels can exert direct “neuroprotective” actions—pertinent are several studies in vivo and rat brain organotypic cultures, in which antecedent or preconditioning exposure to moderate alcohol neuroprotects against ischemia, endotoxin, β-amyloid, a toxic protein intimately associated with Alzheimer’s, or gp120, the neuroinflammatory HIV-1 envelope protein. The alcohol-dependent neuroprotected state appears linked to activation of signal transduction processes potentially involving reactive oxygen species, several key protein kinases, and increased heat shock proteins. Thus to a certain extent, moderate alcohol exposure appears to trigger analogous mild stress-associated, anti-inflammatory mechanisms in the heart, vasculature, and brain that tend to promote cellular survival pathways.

The past decade has witnessed a number of exciting developments in the field of mitochondrial dynamics - a phenomenon in which changes in mitochondrial shape and movement impact on cellular physiology and pathology. By undergoing fusion and fission, mitochondria are able to change their morphology between elongated interconnected networks and discrete fragmented structures, respectively. The cardiac mitochondria, in particular, have garnered much interest due to their unique spatial arrangement in the adult cardiomyocyte, and the multiple roles they play in cell death and survival. In this article, we review the role of the mitochondrial fusion and fission proteins as novel therapeutic targets for treating cardiovascular disease.

Among critically ill patients, several physio-pathological processes such as global and local hypo-perfusion, hypoxia, endothelial injury and acidosis have been associated with the production and release of large amounts of reactive oxygen species (ROS) in a non regulated fashion. Although in physiologic conditions ROS influence intracellular processes and participate in the defense against infectious organism, in critically ill conditions they are associated with potential oxidative damage over cellular structures and with persistent activation of the inflammatory response. Mechanisms associated with oxidative damage are activation of the macrophage-monocyte system and neutrophils, ischemia-reperfusion events and intracellular ROS production. Endogenous compounds, mainly enzymes, and dietary components act as antioxidant. Several studies show that in critically ill patients increase levels of ROS or reduction of antioxidant levels are related to disease severity. In animal models of critical diseases, antioxidant therapy has shown to reduce mortality. Nevertheless, there are few studies in humans that only show improvements in hemodynamic variables, reduction in inflammatory mediators levels, decreases in oxidized compounds and that suggest a lower incidence of multiple organ failure (Rev Méd Chile 2006; 134: 649-56). (Key words: Multiple organ failure; Oxidative stress; Reactive oxygen specias) Recibido el 15 de julio, 2005. Aceptado el 29 de noviembre, 2005.

In the present study, we observed expression and changes of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the gerbil hippocampal CA1 region, but not in the CA2/3 region, after 5 min of transient forebrain ischemia. In blood, corticosterone levels were increased biphasically at 30 min and 12 h after ischemia/reperfusion, and thereafter its levels were decreased. In the sham-operated group, MR and GR immunoreactivities were weakly detected in the CA1 region. By 3 days after ischemia, MR and GR were not significantly altered in the CA1 region: at 12 h after ischemia, GR was expressed in a few neurons in the CA1 region, whereas MR was not expressed in any neurons after ischemic insult. From 4 days after ischemia, MR and GR immunoreactivities were detected in astrocytes and microglia in the CA1 region, and at 7 days after ischemia, MR and GR immunoreactivities peaked in the hippocampal CA1 region. At this time, 55% of astrocytes and 30% of microglia showed MR immunoreactivity, and 20% of astrocytes and 40% of microglia showed GR immunoreactivity. Western blot analyses showed that the pattern of changes in MR and GR protein levels was similar to the immunohistochemical changes observed after transient forebrain ischemia. From 4 days after ischemia, MR and GR protein levels were increased time-dependently after ischemia. In conclusion, enhanced MR and GR expressions in astrocytes and microglia were detected in the hippocampal CA1 region 4-7 days after ischemia/reperfusion. At this time, GR immunoreactivity was abundant in microglia, whereas MR immunoreactivity was prominent in astrocytes. The specific distribution of corticosteroid receptors in the astrocytes and microglia may be associated with the differences of MR and GR functions against ischemic damage. #

Mitochondria have long been known to be the gatekeeper of cell fate. This is particularly so in the response to acute ischaemia-reperfusion injury (IRI). Following an acute episode of sustained myocardial ischaemia, the opening of the mitochondrial permeability transition pore (MPTP) in the first few minutes of reperfusion, mediates cell death. Preventing MPTP opening at the onset of reperfusion using either pharmacological inhibitors (such as cyclosporin-A [CsA]) or genetic ablation has been reported to reduce myocardial infarct (MI) size in animal models of acute IRI. Interestingly, the endogenous cardioprotective intervention of ischaemic conditioning, in which the heart protected against MIby applying cycles of brief ischaemia and reperfusion to either the heart itself or a remote organ or tissue, appears to be mediated through the inhibition of MPTP opening at reperfusion. Small proof-of-concept clinical studies have demonstrated the translatability of this therapeutic approach to target MPTP opening using CsA in clinical settings of acute myocardial IRI. However, given that CsA is a not a specific MPTP inhibitor, more novel and specific inhibitors of the MPTP need to be discovered- the molecular identification of the MPTP should facilitate this. In this article, we review the role of the MPTP as a target for cardioprotection, the potential mechanisms underlying MPTP inhibition in the setting of ischaemic conditioning, and the translatability of MPTP inhibition as a therapeutic approach in the clinical setting.

Recent studies demonstrate that an acute diffusion-weighted imaging lesion volume >70 cm(3) predicts poor outcome in patients with stroke. We sought to determine if this threshold could identify patients treated with intra-arterial therapy who would do poorly despite reperfusion. In patients with initial infarcts <70 cm(3), we sought to determine what effect recanalization and time to recanalization had on infarct growth and functional outcome. We retrospectively studied 34 consecutive patients with anterior circulation stroke who underwent pretreatment diffusion-weighted imaging and perfusion-weighted imaging and subsequent intra-arterial therapy. Recanalization success and time to recanalization were recorded. Initial diffusion-weighted imaging and mean transit time lesion and final infarct volumes were determined. Patients were stratified based on initial infarct volume, recanalization status, and time to recanalization. Statistical tests were performed to assess difference...

Az ayahuasca egy kétkomponensû növényi fôzet, amelynek fô hatóanyagai a dimetiltriptamin (DMT) és β-karbolin-származékok (harmin és tetrahidroharmin). Az Amazonas vidékén évszázadok óta ismert és használt etnomedicinális szer a testi, lelki, társadalmi és spirituális problémák megoldására. Az utóbbi két évtizedben világszerte egyre nagyobb laikus és tudományos érdeklôdés mutatkozik a fôzet terápiás célú alkalmazása iránt. Cikkünk tárgyalja az ayahuasca orvosi felhasználásának lehetôségeit és mindezek sejtbiológiai hátterét, fókuszban a DMT σ-1-receptoron mediált hatásaival. Az ayahuasca terápiás effektusának vizsgálata számos metodikai, financiális, szabályozási és szociokulturális nehézségbe ütközik.

Objectives Renal ischemia followed by reperfusion leads to acute renal failure in both native kidneys and renal allograft. We investigated the effect of curcumin on ischemia-reperfusion (I/R) injury and the antioxidant effects of curcumin in rats. Methods Thirty rats were randomly divided into five experimental groups (control, sham, curcumin, I/R and I/R + curcumin, n = 6 each). Curcumin was administered (200 mg kg−1) orally to curcumin and I/R + curcumin groups for 7 days. Then, the rats were subjected to bilateral renal ischemia for 45 min and followed by reperfusion for 24 h. All rats were killed and kidney function tests, serum and tissue nitric oxide (NO), protein carbonyl (PC), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels were determined. Histopathological examinations were also performed. Results Curcumin significantly improved the urea and cystatin C levels in I/R + curcumin group compared to I/R group (p < 0.05). Reduction of serum GSH-Px was significantly improved by curcumin (p < 0.001), but SOD enzyme activity did not alter (p > 0.05). Treatment with curcumin also resulted in significant reduction in serum and tissue MDA, NO and PC and for tissue that were increased by renal I/R injury (p < 0.001 for serum and p < 0.05 for tissue, respectively). In histological examination, the rats treated with curcumin had nearly normal morphology of the kidney. Conclusions Based on our results, it can be concluded that curcumin protects the kidneys against I/R injury via its antioxidant effects.

Mitochondrial membrane permeabilization (MMP) is commonly regarded as the "point-of-no-return" in the cascade of events that delineate the intrinsic pathway of apoptosis. MMP leads to the functional impairment of mitochondria and to the release into the cytosol of toxic proteins that are normally confined within the mitochondrial intermembrane space. These include direct activators of caspases and caspase-independent effectors of the cell death program. MMP has been implicated in a plethora of pathophysiological settings. In particular, MMP contributes to both the immediate and delayed phases of cell loss that follow acute neuronal injury by ischemia/reperfusion or trauma. Although preventing MMP a priori would be the most desirable therapeutic choice, prophylactic interventions are rarely (if ever) achievable in the treatment of stroke and trauma patients. Conversely, interventions that block the post-mitochondrial phase of apoptosis (if administered within the first few hours after the accident) hold great promises for the development of novel neuroprotective strategies. In animal models of acute neuronal injury, the inhibition of caspases, apoptosis-inducing factor (AIF) and other apoptotic effectors can confer significant neuroprotection. Our review recapitulates the results of these studies and proposes novel strategies of inhibiting postmitochondrial apoptosis in neurons.

It has been previously reported that Nigella sativa oil (NSO) and thymoquinone (TQ), active constituent of N. sativa seeds oil, may prevent oxidative injury in various models. Therefore, we considered the possible effect of TQ and NSO on lipid peroxidation level following cerebral ischemia-reperfusion injury (IRI) in rat hippocampus. Male NMRI rats were divided into nine groups, namely, sham, control, ischemia and ischemia treated with NSO or TQ. TQ (2.5, 5 and 10 mg/kg), NSO (0.048, 0.192 and 0.384 mg/kg), phenytoin (50 mg/kg, as positive control) and saline (10 ml/kg, as negative control) were injected intraperitoneally immediately after reperfusion and the administration was continued every 24 h for 72 h after induction of ischemia. The transient global cerebral ischemia was induced using four-vessel-occlusion method for 20 min. Lipid peroxidation level in hippocampus portion was measured as malondialdehyde (MDA) based on its reaction with thiobarbituric acid (TBA) following ischemic insult. The transient global cerebral ischemia induced a significant increase in TBA reactive substances (TBARS) level (po0.001), in comparison with sham-operated animal. Pretreatment with TQ and NSO were resulted a significant decrease in MDA level as compared with ischemic group (66.971.5 vs. 29772.5 nmol/g tissue for TQ, 10 mg/kg; po0.001 and 153.571.3 nmol/g tissue for NSO, 0.384 mg/kg; po0.001).

Intestinal ischemia-reperfusion (I/R) is associated with various pathological conditions and surgical procedures. These conditions and procedures can cause disruption of intestinal barrier, impairment of gut motility and an increase in intestinal permeability. Data suggest that vascular integrity and intestinal barrier function are severely damaged due to reduced endothelial nitric oxide synthase (eNOS) activity. Apparently, reduced eNOS activity leads to decrease in nitric oxide (NO) production. Reactive oxygen species (ROS), produced during I/R, can damage cell membrane and subcellular structures, and lead to cell death and necrosis. Thus, therapeutic strategies to prevent I/R injury are focusing on antioxidant treatment and NO supplementation [1,2]. The present study aims to test whether the combination of melatonin which is a strong antioxidant and L-arginine which is an NO precursor is more effective or not in prevention of I/R injury.

Malbouisson LMS, Santos LM, Auler Jr JOC, Carmona MJC -Proteção Miocárdica em Cirurgia Cardíaca JUSTIFICATIVA E OBJETIVOS: A proteção miocárdica define o conjunto de estratégias que objetivam atenuar a intensidade da lesão de isquemia-reperfusão miocárdica durante a cirurgia cardíaca e suas conseqüências sobre a função miocárdica. Um melhor entendimento dos fenômenos fisiopatológicos relacionados à isquemia-reperfusão miocárdica e da cardioproteção promovida por determinados fármacos e técnicas anestésicas tem dado ao anestesiologista papel importante na proteção miocárdica durante o procedimento cirúrgico. O objetivo desta revisão foi abordar os mecanismos de lesão miocárdica e as modalidades de proteção miocárdica com enfoque para a técnica anestésica. CONTEÚDO: São abordados os mecanismos de lesão miocárdica durante os eventos de isquemia-reperfusão e suas conseqüências clínicas assim como às técnicas de proteção realizadas durante a cirurgia cardíaca. Ênfase especial é dada aos fármacos e técnicas anestésicas, como anestésicos halogenados, opióides e fármacos adjuvantes, pois estes têm mostrado efeitos cardioprotetores em cirurgia cardíaca. CONCLUSÕES: A associação de técnica anestésica adequada com agentes anestésicos cardioprotetores às técnicas habituais de proteção miocárdica realizadas pelo cirurgião pode contribuir para prevenção de disfunção miocárdica e promover melhor recuperação no período pós-operatório. SUMMARY Malbouisson LMS, Santos LM, Auler Jr JOC, Carmona MJC -Myocardial Protection in Cardiac Surgery

Transient cerebral ischemia kills CA1 pyramidal cells of the hippocampus, whereas most CA1 interneurons survive. It has been proposed that calcium-binding proteins, neurotrophins, and/or inhibitory neuropeptides protect interneurons from ischemia. However, different synaptic responses early after reperfusion could also underlie the relative vulnerabilities to ischemia of pyramidal cells and interneurons. In this study, we used gramicidin perforated patch recording in ex vivo slices to investigate c-aminobutyric acid (GABA) synaptic function in CA1 pyramidal cells and interneurons 4 h after a bilateral carotid occlusion accompanied by hypovolemic hypotension. At this survival time, the amplitudes of both miniature inhibitory postsynaptic currents (mIPSCs) and GABA-evoked currents were reduced in CA1 pyramidal cells, but not in CA1 interneurons. In addition, the mean rise time of mIPSCs was reduced in pyramidal cells. The reversal potential for the GABA current (E GABA ) did not shift toward depolarizing values in either cell type, indicating that the driving force for chloride was unchanged at this survival time. We conclude that early during reperfusion GABAergic neurotransmission is attenuated exclusively in pyramidal neurons. This is likely explained by reduced GABA A receptor sensitivity or clustering and possibly also reduced GABA release, rather than by an elevation of intracellular chloride. Impaired GABA function may contribute to ischemic neuronal death by enhancing the excitability of CA1 pyramidal cells and facilitating N-methyl-D-aspartic acid channel opening. Therefore, normalizing GABAergic function might be a useful pharmacological approach to counter excessive, and potentially excitotoxic, glutamatergic activity during the postischemic period.

The mitochondrial oxidative phosphorylation (OxPhos) system plays a key role in energy production, the generation of free radicals, and apoptosis. A lack of cellular energy, excessive radical production, and dysregulated apoptosis are found alone or in combination in most human diseases, including neurodegenerative diseases, stroke, cardiovascular disorders, ischemia/reperfusion, and cancer. In the context of its relevance to human disease, this article reviews current knowledge about the regulation of OxPhos with a focus on cell signaling and discusses identified phosphorylation sites with the aid of crystal structures of OxPhos complexes. Several recent studies have shown that all OxPhos components can be phosphorylated; even the small electron carrier cytochrome c is tyrosine phosphorylated in vivo. We propose that in higher organisms, in contrast to bacteria, cell signaling pathways are the main regulator of energy production, triggered for example by hormones. Pathways that have been identified to act on OxPhos include protein kinases A and C and growth factor activated receptor tyrosine kinase signaling. Present knowledge about kinases and phosphatases that execute signals at the level of the mitochondrial OxPhos system, and newly emerging concepts, such as the translocation of kinases to the mitochondria upon stimulation of a signaling pathway, are discussed.

We performed a systematic review of the literature to establish whether revascularisation of the left subclavian territory is necessary when this artery is covered by a stent. We retrieved data from 99 studies incorporating 4906 patients. Incidences of left-arm ischaemia (0.0% vs 9.2%, p = 0.002) and stroke (4.7% vs 7.2%, p < 0.001) were significantly less following revascularisation, although mortality (10.5% vs 3.4%, p = 0.032) and endoleak incidence (25.8% vs 12.6%, p = 0.008) were increased. No significant differences in spinal-cord ischaemia were seen. Revascularisation may reduce downstream ischaemic complications but can cause significant risk. Indications must be carefully considered on an individual patient basis. #

The developmental pattern of the cartilage canal blood supply to epiphyseal growth cartilage has been linked to osteochondrosis (OC) in the tarsus of foals. This pattern has not yet been described in the distal femur, another site frequently affected by OC. Objective: To describe the developmental pattern of the blood supply to the distal femoral epiphyseal growth cartilage in 8 Standardbred foals age 0-7 weeks. Methods: One foal was sacrificed weekly from birth to age 7 weeks (n = 8) to undergo a barium perfusion procedure to demonstrate vessels within cartilage canals of one hindlimb. The distal end of the femur was cleared in methyl salicylate and perfused vessels were studied in the intact bones. Each distal femur was then sawed into 5 mm thick slabs in the transverse plane, and the slabs decalcified and radiographed. Finally, the lateral trochlear ridge was separated from each slab and examined histologically. Results: The cartilage canal blood supply regressed with increasing age, but several regions remained vascularised in the oldest foal at age 7 weeks. Vessels arose from perichondrial and subchondral arterial sources, and coursed perpendicular or parallel to the ossification front. The midsection of parallel vessels became incorporated into the ossification front during growth. Anastomoses formed and vessels within the distal portion of canals with an original perichondrial source shifted to use subchondral vessels as their arterial source. Both parallel and perpendicular vessels therefore traversed the ossification front to enter cartilage canals. No histological lesions were observed in sections from any of the foals. Conclusion: The same anatomical feature (traversing the ossification front to enter cartilage canals) reported to render vessels vulnerable to failure in the tarsus was also present in the distal femur of foals. Potential relevance: OC may occur by the same pathogenetic mechanism in the distal femur as in the tarsus of foals.

Stroke is a worldwide major cause of mortality and morbidity. Preclinical studies have identified over 1000 molecules with brain-protective properties. More than 200 clinical trials have evaluated neuroprotective candidates for ischemic stroke yet, to date almost all failed, leading to a re-analysis of treatment strategies against stroke. An emerging view is to seek combinatory therapy, or discovering mol- ecules able to stimulate multiple protective and regenerative mechanisms. A pertinent experimental approach to identify such candidates is the study of brain preconditioning, which refers to how the brain protects itself against ischemia and others stress-inducing stimuli. The recent discovery that nutrients like alpha-linolenic acid (ALA is an essential omega-3 polyunsaturated fatty acid required as part of our daily diet), may be an efficient brain preconditionner against stroke fosters the novel concept of brain preconditioning by nutraceuticals.
This review stresses the underestimated role of nutrition in preventing and combating stroke. Al- though there is a consensus that increased consumption of salt, fatty foods and alcoholic beverages may promote pathologies like hypertension, obesity and alcoholism – all of which are well known risk factors of stroke – few risk factors are attributed to a deficiency in an essential nutrient in the diet. The ALA deficiency observed in the Western modern diets may itself constitute a risk factor.
This review outlines how ALA supplementation by modification of the daily diet prevented mortal- ity and cerebral damage in a rodent model of ischemic stroke. It also describes the pleiotropic ability of ALA to trigger responses that are multicellular, mechanistically diverse, resulting in neuronal protec- tion, stimulation of neuroplasticity, and brain artery vasodilation. Overall, this review proposes a promising therapeutic opportunity by integrating a nutritional-based approach focusing on enriching the daily diet in ALA to prevent the devastating damage caused by stroke.

The vast majority of research on dimethyltryptamine (DMT) has targeted its psychotropic properties and serotonergic activity, with little focus on its effects beyond the nervous system and at other receptor molecules. The recent discovery that DMT is an endogenous agonist of the sigma-1 receptor (sigmaR-1) (Fontanilla et al., 2009) may shed light on yet undiscovered physiological and therapeutic mechanisms of DMT action and reveal some of its putative biological functions. Since the sigmaR-1 has an extensive role in mitigation of several forms of intracellular stress such as mitochondrion, endoplasmic reticulum, and oxidative stress, as well as protecting against apoptotic cell death and regulating immune processes, one may suppose similar effects from DMT administration. In this chapter, we present an overview of the literature on the effects of sigmaR-1 in cellular bioenergetics with a focus on the processes involved in ischemia-reperfusion injury. Ischemia-reperfusion injury is a complex phenomenon with mechanisms underlying organ transplantation, stroke, myocardial infarct, general brain hypoxia, cardiovascular surgery, neonatology, and cardiopulmonary resuscitation. We conclude that the function of DMT may extend beyond central nervous system activity and

Ischemic stroke remains one of the leading cause of adult death and disability in the United States. Reperfusion of the occluded vessel is the standard of care in the setting of acute ischemic stroke according to established guidelines. Since the introduction of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) in the late 1990s, significant advances have been made in methods to deliver thrombolytic agents and in devices for mechanical recanalization of occluded vessels. Furthermore, improvements in patient selection contribute to achievement of good clinical outcomes after endovascular therapy. This article summarizes findings from recent clinical trials and presents evidencebased guidelines for endovascular interventions in the treatment of ischemic stroke.

Background aims. The Pall Celeris system is a filtration-based point-of-care device designed to obtain a high concentrate of peripheral blood total nucleated cells (PB-TNCs). We have characterized the Pall CelerisederivedTNCsfortheirin vitro and in vivo angiogenic potency. Methods. PB-TNCs isolated from healthy donors were characterized through the use of flow cytometry and functional assays, aiming to assess migratory capacity, ability to form capillary-like structures, endothelial trans-differentiation and paracrine factor secretion. In a hind limb ischemia mouse model, we evaluated perfusion immediately and 7 days after surgery, along with capillary, arteriole and regenerative fiber density and local bio-distribution. Results. Human PB-TNCs isolated by use of the Pall Celeris filtration system were shown to secrete a panel of angiogenic factors and migrate in response to vascular endothelial growth factor and stromal-derived factor-1 stimuli. Moreover, after injection in a mouse model of hind limb ischemia, PB-TNCs induced neovascularization by increasing capillary, arteriole and regenerative fiber numbers, with human cells detected in murine tissue up to 7 days after ischemia. Conclusions. The Pall Celeris system may represent a novel, effective and reliable point-of-care device to obtain a PB-derived cell product with adequate potency for therapeutic angiogenesis.

Injury due to cold ischemia reperfusion (I/R) is a major cause of primary graft non-function following liver transplantation. We postulated that I/R-induced cellular damage during liver transplantation might affect the secretory pathway, particularly at the endoplasmic reticulum (ER). We examined the involvement of ER stress in organ preservation, and compared cold storage in University of Wisconsin (UW) solution and in Institute Georges Lopez-1 (IGL-1) solution. In one group of rats, livers were preserved in UW solution for 8 h at 4 °C, and then orthotopic liver transplantation was performed according to Kamada&#39;s cuff technique. In another group, livers were preserved in IGL-1 solution. The effect of each preservation solution on the induction of ER stress, hepatic injury, mitochondrial damage and cell death was evaluated. As expected, we found increased ER stress after liver transplantation. IGL-1 solution significantly attenuated ER damage by reducing the activation of three ...

In this study, we aimed to investigate the effects of hesperidin and coenzyme Q10 on muscle ischemia/reperfusion injury in a rat model. A total of 28 Sprague-Dawley male rats were divided into four groups: Control, Sham, I/R+CoQ10 and I/R+Hesperidin groups. All rats were anesthetized with xylazine and ketamine. Except for the control group, the left lower limbs of the other 3 groups were applied to 2 hours of ischemia and 2 hours of reperfusion with tourniquet. TNF-α, IL-6, GSH, MDA levels, CAT, GPx, SOD activities were measured in the plasma. The levels of MDA with XO, CAT, SOD activities were determined in tissues. Increases in TNF-α, IL-6 and MDA levels, decreases in the CAT, GPx and SOD activities were significant in the sham group according to the control group but the differences in GSH were insignificant in plasma samples. The decreases in plasma TNF-α, IL-6 and MDA levels, the increases in CAT, GPx and SOD activities were statistically significant in the experimental groups compared to the sham group, but the GSH differences were insignificant. MDA and XO levels were higher in the
experimental groups than in the sham and control groups, CAT and SOD levels decreased, these differences were statistically significant. The results of this study support the possibility that hesperidin and CoQ10 may play a protective role against skeletal muscle injury caused by I/R in rats by reducing oxidative stress. Hence, hesperidin and coenzyme Q10 may be useful adjunctive therapeutic agents in some operations suspected of organ I/R damage.

Context: Some flavonoids have been described as neuroprotectors. Gossypitrin (Gos) is a natural occurring flavonoid and the main bioactive substance from the flowers of Talipariti elatum Sw. (Majagua azul), traditionally used in Cuba as expectorant and antiasthmatic. Only few reports have documented its antioxidant properties.

Aims: To evaluate the antioxidant and cytoprotective effects of Gos against cyanide-induced oxidative stress and cell death in PC12 cells.

Methods: Gos effects on DPPH/ ABTS radical scavenging, ferric reducing power and lipid peroxidation were examined. The ischemia/reperfusion neuronal damage was produced by exposing PC12 cells to KCN in glucose-free medium. Gos was added to the incubation medium 30 min before chemical hypoxia induction. The neuroprotective potential of Gos was assessed by measuring cell viability by the MTT assay, the antioxidant enzymes SOD and CAT, and GSH and lipid peroxidation levels. Rutin (Rut), the well-known antioxidant, was used as a reference compound.

Results: Gos showed a potent intrinsic antioxidant capacity evidenced by low IC50 and EC50 values for DPPH/ABTS/malondialdehyde and ferric reducing power, respectively. Pre-treatment of PC12 cells with Gos, significantly increased their survival against KCN, restored the levels of GSH and the SOD and CAT enzymes activities, as well as reduced the level of lipid peroxidation. Its antioxidant effects were higher than those elicited by Rut.

Conclusions: The results show for the first time the neuroprotective potential of Gos against hypoxic cell damage, probably associated to its antioxidant effects.

Saffron and its constituents have been shown to decrease ischemia-reperfusion (I/R) injury in kidney or brain tissues. In this study, the effects of saffron ethanolic extract and its constituents, crocin and safranal, were evaluated in skeletal muscle during I/R injury. Hind limb ischemia was induced using clamping the common femoral artery and vein. After 2 h ischemia, the clamp of the femoral vessels of animals was taken off and the animal underwent 1h reperfusion. Muscle injuries were evaluated by recording of the electromyographic (EMG) potentials and performing some biochemical analysis including thiobarbituric acid reactive substances (TBARS), total sulfhydryl (SH) groups and antioxidant capacity of muscle (using FRAP assay). The ethanolic extract of saffron (5, 20 and 80 mg kg À1 ), crocin (50, 200 and 400 mg kg À1 ), safranal (0.1, 0.25 and 0.5 ml kg À1 ) and normal saline (10 ml kg À1 ) were administered intraperitoneally 1 h prior reperfusion. The average peak-to-peak amplitude during I/R was significantly increased in extract, crocin and safranal groups in comparison with control-ischemic group. Following saffron, crocin and safranal administration, the total SH contents and antioxidant capacity were elevated in muscle flap. The MDA level was declined significantly in test groups. It is concluded that saffron extract and its constituents show a protective effect against lower limb I/R in rat.