KFMC FACULTY OF MEDICINE, BASIC MEDICAL SCIENCES

This study was performed to investigate the protective and therapeutic effects of resveratrol (RES) against CdCl 2induced toxicity in rat testes. Seven experimental groups of adult male rats were formulated as follows: A) controls+NS, B) control+vehicle (saline solution of hydroxypropyl cyclodextrin), C) RES treated, D) CdCl 2 +NS, E) CdCl 2 +vehicle, F) RES followed by CdCl 2 and M) CdCl 2 followed by RES. At the end of the protocol, serum levels of FSH, LH and testosterone were measured in all groups, and testicular levels of TBARS and superoxide dismutase (SOD) activity were measured. Epididymal semen analysis was performed, and testicular expression of Bcl-2, p53 and Bax was assessed by RT-PCR. Also, histopathological changes of the testes were examined microscopically. Administration of RES before or after cadmium chloride in rats improved semen parameters including count, motility, daily sperm production and morphology, increased serum concentrations of gonadotropins and testosterone, decreased testicular lipid peroxidation and increased SOD activity. RES not only attenuated cadmium chloride-induced testicular histopathology but was also able to protect against the onset of cadmium chloride testicular toxicity. Cadmium chloride downregulated the anti-apoptotic gene Bcl2 and upregulated the expression of pro-apoptotic genes p53 and Bax. Resveratrol protected against and partially reversed cadmium chloride testicular toxicity via upregulation of Bcl2 and downregulation of p53 and Bax gene expression. The antioxidant activity of RES protects against cadmium chloride testicular toxicity and partially reverses its effect via upregulation of BCl2 and downregulation of p53 and Bax expression.

Problem statement: Citrullus Colocynthis (L.) Schrab (cucurbitaceae family) (Handal) is a fruit commonly known as bitter apple or bitter cucumber. Traditionally, Citrullus colocynthis has been used for the treatment of diabetes. In particular, the acute effect and rout of administration of ethanol extract of the seedless pulp in vivo remains untested. We investigated the effect of different routs of administration and their hypoglycemic and insulinotropic effects of ethanol/water (20/80 V/V) extract of the dried seedless pulp of Citrullus colocynthis (L.) Schrab on normal and alloxan-induced diabetic rats. Approach: Rats were divided into two groups, normal and diabetic rats. Non-diabetic rats were fasted for 18 h before the beginning of the experimental procedure. About 250 µL of normal saline (i.e., vehicle) was administered to control groups either i.p. (Group I) or orally (Group III) using modified feeding canula. As 250 µL pulp extract was administered i.p. (Group II) or orally (Group IV). Five min, after the administration of the extract or vehicle, an Intraperitoneal Glucose Tolerance Test (IPGTT) was conducted (1.5 g glucose/kg) on groups I, II, III and IV, but not Groups V or VI. Alloxan-induced diabetic rats were fasted for 6 h before the beginning of the experimental procedure. They were divided into control (Group V) and treated groups (Group VI), each of 6 rats. As 250 µL of the extract (equivalent to 300 mg kg −1) was administered orally to alloxan treated-group, while 250 µL of the vehicle was administrated orally to the animals of control group. Serum samples were collected at 0, 1, 2, 3, 4 and 6 h following the treatment and were used for glucose and insulin determination. Results: Oral, but not intraperitonial (i.p.) administration of ethanol extract (300 mg kg −1) resulted in acute, significant (p<0.05) and time-dependent changes in rat serum glucose and insulin levels in both normal and alloxan-induced diabetic rats. In extract-treated alloxan-free rats, a maximum of 32.9% reduction in serum glucose levels was observed following Intraperitonial Glucose Tolerance Test (IPGTT) using glucose-oxidase assay. A maximum reciprocal increase of 59.5% in serum insulin levels following IPGTT was determined by ELISA. Further, in alloxan/ethanol extract-treated group, a maximum of 31% reduction in serum glucose levels as well as 370.2% increase in serum insulin levels following IPGTT were observed. Conclusion: These results demonstrated that oral administration of the ethanol extract of the dried seedless pulp of Citrullus colocynthis had normo-hypoglycemic (i.e., in normal rats), antihyperglycemic as well as insulinotropic actions in alloxan-induced diabetic rats.

Background Citrullus colocynthis pulp seedless extract has been demonstrated to have antihyperglycemic and insulinotropic effects. Problem statement: The mechanism(s) underlying the antihyperglycemic and insulinotropic effects have not been investigated to date. Approach: The influence of Citrullus colocynthis pulp extract administered orally was studied in alloxan diabetic white albino rats. Rats were divided into four groups, the first group was normal non diabetic rats given normal saline orally and was named control group, the second group was diabetic rats given normal saline orally and were named normal saline treated-diabetic rats, the third and fourth group were diabetic rats treated with the pulp extract or glybenclamide (a positive control) orally. Plasma glucose, glycosylated hemoglobin and insulin were determined in all groups. The effect of pulp extract of this plant on liver and kidney tissues was also studied. The amount of insulin in β-cells of the Islets of Langerhans in all groups was assessed using immunohistochemistry procedure. Results: Treatment of diabetic rats with Citrullus colocynthis pulp extract (300 mg kg −1 body weight) resulted in a significant decrease in plasma glucose, glygosylated Hb and increased insulin levels. This significant increase in insulin may explain the increase in the activity of liver hexokinase, with concomitant decrease of glucose 6-phosphatase and fructose-1,6-bisphosphatase. Immunohistochemistry procedure showed that the amount of insulin in β-cells of the islets of Langerhans is greater in Citrullus colocynthis treated-diabetic rats in comparison to non-treated diabetic rats. Conclusion: The present study clearly demonstrated that the folk medicinal plant Citrullus colocynthis pulp extract possesses a hypoglycemic effect, through an increase in insulin production and the subsequent increase in activity of glycolytic enzyme and decrease in activity of enzymes of gluconeogenesis. The present study also showed that the pulp extract of this plant to may have protective effects on the liver and kidney.

Problem statement: The goal of the current investigation was to clarify the effects of Citrullus colocynthis pulp extract on the structure of the liver of diabetic rats at both light and scanning electron microscopic levels. Approach: Forty-eight adult male albino rats were equally allocated into four groups: Group1: control, Group 2: Citrullus colocynthis-treated, Group 3: diabetic rats and Group4: diabetic rats treated with Citrullus colocynthis. All treatments were administered via an intragastric tube. Diabetes was induced in the rats of groups 3 and 4 by an intraperitoneal injection with alloxan. Results: The liver of Citrullus colocynthis-treated rats revealed minor histological changes versus the control animals. In group 3 animals, diabetes caused degenerative alterations in the form of disorganization of the hepatic cords, cytoplasmic vacuolization and pyknosis of the nuclei of hepatocytes and inflammatory cell infiltration. Scanning electron microscope examination of these livers revealed numerous lipid droplets within hepatocytes, damaged blood sinusoids and hemorrhage of erythrocytes between hepatocytes and inside Disse's spaces. On the other hand, the normal histological and scanning ultrastructural features were nearly resumed in the liver of diabetic rats treated with Citrullus colocynthis pulp extract. Conclusion: The present study proved a lessening effect of Citrullus colocynthis pulp extract on the liver of diabetic rats. In light of these advantageous influences, it is advisable to widen the scale of its use in a trial to alleviate the diabetic hepatic adverse effects.

Problem statement: Cadmium is one of the most dangerous occupational and environmental toxins. It is found in drinking water, atmospheric air and even in food. Cadmium is reported to be very toxic to biological systems. Until now in treating intoxication with this metal, chelating Compounds have been used, burdened with numerous undesirable symptoms. For this reason, many researches are carried out in many countries to find natural-made compounds that help in the protection against cadmium induced toxicity with fewer or no side effects. This study was conducted to demonstrate the effect of daily oral Camel's milk administration against Cadmium chloride induced toxicity in white albino rats. Approach: White albino rats of both sexes (230-250 g) were housed in standard metal cages (6 rats/cage). The experimental rats (6 in each group) distributed into two experimental groups with a shared control group received only normal saline orally (Group 1). In experimental first group a daily dose (10 mg kg  1 body weight) of cadmium chloride was orally administrated to the rats for 21 days and named Cadmium chloride treated rats. In experimental second group, the same concentrations of cadmium chloride was dissolved in 2 mL of early morning fresh Camel's milk and the whole solution was administered into the experimental rats for 21 days and named Camel's milk cadmium chloride treated group. Water and food were provided ad libitum. Results: The data indicated that, in experimental Cadmium chloride treated rats, serum albumin, calcium and blood hemoglobin were decreased compared with control group received normal saline only. Moreover, Camel's milk administration with cadmium chloride showed a significant improvement of albumin, hemoglobin and calcium levels in the serum of the rats compared with cadmium chloride treated rats. Serum iron, sodium, chloride and urea levels were significantly increased in cadmium chloride treated rats compared with control group, while the addition of camel's milk to cadmium chloride decreased the high levels of these serum parameters in the treated rats. The enzyme activities of serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and serum Alkaline Phaospatase (ALP) were significantly increased by orally administration of cadmium chloride compared with control group, while adding Camel's milk to cadmium chloride decreased the high levels of these enzymes comparing with the cadmium chloride treated rats. Cadmium chloride administration resulted in a high concentration of lipid peroxidation markers; TBARS and Hydroperoxides in comparison to control group, adding camel's milk to the cadmium chloride restored the levels of these markers to their normal levels in comparing to Cadmium chloride treated rats. Also treatment with cadmium chloride alone caused a significant decrease in both the enzymatic and nonenzymatic markers of oxidative stress (superoxide dismutase and catalase) and reduced glutathione, respectively in the liver tissues of treated rats, while the administration of camel's milk with cadmium chloride increased and restored their levels to near normal in comparing with cadmium chloride treated rats. These results demonstrated that camel's milk had a protective effect against the toxicity induced by cadmium chloride. Conclusion: the above results indicated a protective effect of camel's milk oral administration against cadmium induced toxicity in white albino rats.

This study was performed to investigate the protective and therapeutic effects of resveratrol (RES) against CdCl 2induced toxicity in rat testes. Seven experimental groups of adult male rats were formulated as follows: A) controls+NS, B) control+vehicle (saline solution of hydroxypropyl cyclodextrin), C) RES treated, D) CdCl 2 +NS, E) CdCl 2 +vehicle, F) RES followed by CdCl 2 and M) CdCl 2 followed by RES. At the end of the protocol, serum levels of FSH, LH and testosterone were measured in all groups, and testicular levels of TBARS and superoxide dismutase (SOD) activity were measured. Epididymal semen analysis was performed, and testicular expression of Bcl-2, p53 and Bax was assessed by RT-PCR. Also, histopathological changes of the testes were examined microscopically. Administration of RES before or after cadmium chloride in rats improved semen parameters including count, motility, daily sperm production and morphology, increased serum concentrations of gonadotropins and testosterone, decreased testicular lipid peroxidation and increased SOD activity. RES not only attenuated cadmium chloride-induced testicular histopathology but was also able to protect against the onset of cadmium chloride testicular toxicity. Cadmium chloride downregulated the anti-apoptotic gene Bcl2 and upregulated the expression of pro-apoptotic genes p53 and Bax. Resveratrol protected against and partially reversed cadmium chloride testicular toxicity via upregulation of Bcl2 and downregulation of p53 and Bax gene expression. The antioxidant activity of RES protects against cadmium chloride testicular toxicity and partially reverses its effect via upregulation of BCl2 and downregulation of p53 and Bax expression.

Result: HA rats had significantly (P<0.05) lower serum T3 (17.14%), T4 (13.75%), TSH (39.29%) and total cholesterol (15.84%) and LDL (60.90%).There were no significant differences in TAG or HDL. All tissues from HA rats showed significant decreases in SOD and CAT activities compared to LA rats. These rats showed significantly higher oxidative stress in the lungs and the liver, but lower oxidative stress in the kidney and no difference in the testes. Conclusion: Living at high altitude environment results in impaired thyroid function and lipid metabolism and causes increased tissue oxidative stress.

To study the effect of chronic exposure to native high altitude (HA) on blood pressure, and to investigate the underlying mechanism of action. This study was carried out between February and April 2011. A total of 20 male rats were divided into 2 groups (n=10 rats). The low altitude (LA) group were rats born and lived in an LA environment at King Saud University, College of Pharmacy, Riyadh, Kingdom of Saudi Arabia (KSA), and the HA group were rats born in the same LA area, then acclimatized to HA area in Physiology Department, King Khalid University, College of Medicine, Abha, KSA for 90 days. At the end of day 90, hematocrit, plasma renin activity, aldosterone, norepinephrine and vasopressin levels were determined in both groups. Invasive arterial blood pressure was also measured, and fractional excretion of sodium (FENa), and potassium (FEK) were calculated. The quantitative real time-polymerase chain reaction of renin was carried out in the kidneys of both rat groups. When compa...

Myocardial infarction (MI) due to sudden occlusion of a major coronary artery leads to a complex series of events that result in left ventricle (LV) impairment eventual heart failure. Therapeutic options are limited to reverse such trends post MI. The aim of this study was to compare the acute cardioprotective effects of the antioxidants, resveratrol (RES) and coenzyme Q10 (CoQ10), either individually or in combination, on infracts size, LV hemodynamics, inflammation and oxidative stress markers in rats with experimentally induced MI. Male Wistar rats were randomly divided into six groups: control without surgery, sham without occlusion, MI without antioxidants, RES pre-treated then MI (20 mg/kg, orally), CoQ10 then MI (20 mg/kg, intramuscular.), and combined RES and CoQ10 then MI with (each group n = 10). Pretreatment commenced 7 days prior to the permanent occlusion of the left anterior descending (LAD) coronary artery. Infarct area, hemodynamics, inflammation and oxidative stress...

Thyroid hormones play an important role in cell growth and differentiation and regulation of oxygen consumption and thermogenesis. The effect of altitude and vitamin supplementation on thyroid hormone levels in animals or humans performing acute exhaustive exercise have not been investigated before. Therefore, we thought to test whether exhaustive exercise-induced stress with antioxidant supplementation was capable of modulating the level of thyroid hormones at different altitudes. Serum levels of T4 (Thyroxin), T3 (Triiodothyronine), and TSH (Thyroid Stimulating Hormone) were measured in rats (N=36) born and bred in low altitude (600 m above sea level) and high altitude (2200 m above sea level) following forced swimming with or without vitamins C and E (25 mg/kg) pre-treatments. Thyroid levels were significantly decreased in resting rats at high altitude compared to low altitude, and swimming exercise moderately increased T3 and TSH at both high and low altitudes, whereas T4 was ma...

Increased oxidative stress and hormonal imbalance have been hypothesized to underlie infertility in obese animals. However, recent evidence suggests that Ghrelin and Stem Cell Factor (SCF) play an important role in fertility, in lean individuals. Therefore, this study aimed at investigating whether changes in the levels of Ghrelin and SCF in rat testes underlie semen abnormal parameters observed in obese rats, and secondly, whether endurance exercise or Orlistat can protect against changes in Ghrelin, SCF, and/or semen parameters in diet induced obese rats. Obesity was modelled in male Wistar rats using High Fat Diet (HFD) 12-week protocol. Eight week-old rats (n=40) were divided into four groups, namely, Group I: fed with a standard diet (12 % of calories as fat); Group II: fed HFD (40 % of calories as fat); Group III: fed the HFD with a concomitant dose of Orlistat (200 mg/kg); and Group IV: fed the HFD and underwent 30 min daily swimming exercise. The model was validated by measu...

Thiel embalming has been gaining a great deal of worldwide attention. Its long-lasting life-like quality enables multiple applications in surgical training programs. The standard process of Thiel embalming, which involves perfusion of embalming fluid in fresh cadavers through cannulation of the arterial and venous systems could be difficult in some areas of the world where fresh body donation rates are low or banned. This study will assess the ability to Thiel embalm fresh frozen mice as an animal model as a solution for the lack of fresh cadavers. The ability of Thiel embalming frozen tissue would enable areas in the world where they do not have access to recently diseased donated cadavers. The study was ethically approved King Fahad Medical City Institutional Review Board. The 20 Mice cadavers were ethically gained from the university of Dundee animal house. They were euthanized ethically by carbon dioxide. They were handled by following the university’s ethical code. The mice wer...

Two to three million pilgrims gather in Makkah annually in the twelfth month of the lunar Islamic year to perform Hajj, the fifth pillar of Islam. During the Rift Valley fever epidemic that occurred in southwestern Saudi Arabia in 2000–2001, a total of 886 cases were reported with ...