Papers by Shanmugam Manoharan
Indian Journal of Pharmacology, 2006
Diabetes mellitus is a major metabolic syndrome characterized by derangement in carbohydrate meta... more Diabetes mellitus is a major metabolic syndrome characterized by derangement in carbohydrate metabolism associated with defect in insulin secretion or action. Alloxan is widely used to induce diabetes mellitus in experimental animals, owing to its ability to destroy the ß-cells of pancreas possibly by generating excess reactive oxygen species. [1] Free radical-mediated biomembrane lipid peroxidation has been implicated in the pathogenesis of many pathological conditions including diabetes mellitus and its complications. Overproduction of lipid peroxidation by-products and insufficient antioxidant potential have been reported in both experimental and human diabetes mellitus. [2] Medicinal plants and their bioactive constituents are used for the treatment of diabetes mellitus throughout the world, especially in countries where access to the conventional treatment of diabetes mellitus is inadequate. A few side effects associated with the use of insulin (hypoglycemia) and oral hypoglycemic agents prompted us to search new bioactive principles from antidiabetic plants used in traditional medicine. Although several medicinal plants have gained importance for the treatment of diabetes mellitus, many remain to be scientifically investigated. Pongamia pinnata (Linn) Pierre is a medium-sized glabrous tree popularly known as Karanja in Hindi, Indian beech in English, and Pongam in Tamil. P. pinnata is an important medicinal plant chiefly found in tidal forests of India and has been largely used in the traditional Indian system of medicine (ayurveda) for bronchitis, whooping cough, rheumatic arthritis, and diabetes. [3] Despite its prominence in ayurvedic medicine, there is a dearth of scientific data on its antihyperglycemic and antilipidperoxidative effects in diabetes mellitus. Thus, the present study was focused on the antihyperglycemic and antilipidperoxidative activities of aqueous extract of P. pinnata flowers (PpFAet) in alloxan-induced diabetic rats. Albino Wistar male rats (7-8 week old, weighing 150-200 g) were used in the present study and housed in the Central Animal House with 12 h light/dark cycle. Standard pellet (Mysore Snack Feed Ltd, Mysore, India) was used as a basal diet during the experiment. The control and experimental animals were provided food and water ad libitum. The Institutional Animal Ethics Committee of the Annamalai University, Annamalai Nagar, India, approved the experimental design. A total of 30 rats were divided into 5 groups of 6 each and treated as follows. Group I-control (2 ml distilled water, orally). Group II-diabetic control (alloxan, 150 mg/kg, i.p). Group III-diabetic + PpFAet (300 mg/kg, orally). Group IV-diabetic+ glibenclamide (600 µg/kg, orally). Group V-PpFAet + distilled water (300 mg/kg, orally).
PubMed, Dec 1, 2005
Background & objective: Overproduction of lipid peroxidation byproducts and disturbances in antio... more Background & objective: Overproduction of lipid peroxidation byproducts and disturbances in antioxidant defense system have been implicated in the pathogenesis of several diseases including oral cancer. Though several studies have been done on the level of lipid peroxidation and antioxidants in oral cancer patients, there are no reports in patients with various clinical stages of oral squamous cell carcinoma. We carried out this study to assess the level of oxidative stress in oral cancer patients with various clinical stages. Methods: Blood samples of 48 adult male oral cancer patients with various clinical stages of oral cancer (stage II to stage IV, 16 of each) and 16 age and sex matched healthy subjects were collected. Plasma and erythrocytes levels of thiobarbituric acid reactive substances (TBARS), vitamin E, reduced glutathione (GSH), and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were assayed using specific colorimetric methods. The statistical comparisons were performed by one way analysis of variance (ANOVA) followed by Student's t-test. Results: Elevated lipid peroxidation and decline in non-enzymatic and enzymatic antioxidants status were noticed in oral cancer patients as compared to healthy subjects. The TBARS levels were gradually increased whereas antioxidants were gradually reduced from stage II to stage IV of oral cancer patients. Interpretation & conclusion: The altered lipid peroxidation in plasma and erythrocytes of oral cancer patients may be related to their compensatory changes in the antioxidants defense system.
Clinica Chimica Acta, Dec 1, 2002
Background: Our aim was to examine the structural integrity of red blood cells in cervical cancer... more Background: Our aim was to examine the structural integrity of red blood cells in cervical cancer patients by measuring the concentrations of thiobarbituric acid reactive substances (TBARS), antioxidant status, cholesterol/phospholipid (C/P) molar ratio, enzyme activity and osmotic fragility of erythrocytes. Methods: This study has been conducted on 32 adult female cervical cancer patients and an equal number of age-and sex-matched normal subjects. Erythrocyte concentrations of lipids, TBARS, vitamin E, reduced glutathione and enzymic activities of catalase and Na + K +-ATPase were measured as well as plasma concentrations of sodium and potassium. The present study also examined the changes in erythrocyte osmotic fragility in cervical cancer patients and normal subjects. The red cell fluidity and permeability were determined by estimating the C/P ratio and Na + K +-ATPase activity, respectively. Results: The release of thiobarbituric acid reactive substances was significantly higher in cervical cancer patients as compared to normal subjects. The increased lipid peroxidation with concomitant decrease in antioxidants was notable in cervical cancer patients. Red blood cells of cervical cancer patients were more fragile than those from normal subjects. Increase in red cell membrane C/P ratio and Na + K +-ATPase activity was noticed in cervical cancer patients as compared to normal subjects. Conclusions: Increased lipid peroxidation, insufficient antioxidant potential and changes in C/P molar ratio as well as activity of Na + K +-ATPase cause structural and functional abnormalities in the erythrocytes of cervical cancer patients.
International Journal of Research in Pharmaceutical Sciences, Oct 22, 2010
Effects of genistein and daidzein, in combination, on the expression pattern of biomolecular mark... more Effects of genistein and daidzein, in combination, on the expression pattern of biomolecular markers (p53, PCNA, VEGF, iNOS, Bcl-2, and Bax) during 7,12-dimethylbenz(a)anthracene (DMBA) induced mammary carcinogenesis in Sprague-Dawley rats.
Archives of Oral Biology, May 1, 2020
International research journal of pharmacy, Jun 28, 2010
The present study was designed to investigate the modifying effects of Mosinone-A on glycoconjuga... more The present study was designed to investigate the modifying effects of Mosinone-A on glycoconjugates (protein bound hexose, hexosamine, total sialic acid and fucose) levels in 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis 0.5% DMBA painting (three times per week) in hamster buccal pouches for 14 weeks resulted in the formation of well developed oral squamous cell carcinoma. We observed 100% tumor formation with marked abnormalities of glycoconjugates status in tumor bearing hamsters as compared to control animals. Oral administration of Mosinone-A at a dose of 2mg/kg body weight, to DMBA painted hamsters on alternate days for 14 weeks, reduced the tumor formation as well as protected the levels of cell surface glycoconjugates in DMBA painted hamsters. The present study thus suggests that Mosinone-A has potent chemopreventive efficacy as well as protected the abnormalities on cell surface glycoconjugates during DMBA induced hamster buccal pouch carcinogenesis
International journal of Nutrition, Pharmacology, Neurological Diseases, 2012
Aim: The aim of this study was to evaluate the protective effect of 18β-glycyrrhetinic acid again... more Aim: The aim of this study was to evaluate the protective effect of 18β-glycyrrhetinic acid against cell surface glycoconjugates (protein-bound hexose, hexosamine, sialic acid, and fucose) abnormalities in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Materials and Methods: Topical application of DMBA three times a week for 14 weeks on the buccal pouches of hamsters resulted in welldeveloped squamous cell carcinoma. Glycoconjugates status in plasma and tumor tissues were estimated using specific and sensitive colorimetric methods. Results: Increases in plasma and tumor tissue glycoconjugates were noticed in hamsters treated with DMBA. Oral administration of glycyrrhetinic acid at a dose of 45 mg/kg body weight restored the status of glycoconjugates in hamsters treated with DMBA. Conclusion: The results of this study suggest that glycyrrhetinic acid might provide protection against cell surface abnormalities during DMBA-induced buccal pouch carcinogenesis in hamsters.
International Journal of Research in Pharmaceutical Sciences, Oct 22, 2010
Chemoprevention is a novel approach to study the anti-initiating and anti-tumor promoting efficac... more Chemoprevention is a novel approach to study the anti-initiating and anti-tumor promoting efficacy of medicinal plants and its active principles. Chemopreventive agents exert their anticancer potential through their anti-lipid peroxidative and antioxidant function. The present study ...
International Journal of Research in Pharmaceutical Sciences, Apr 25, 2012
Cell surface glycoconjugates play an important role in pinocytosis, cell differentiation, intra c... more Cell surface glycoconjugates play an important role in pinocytosis, cell differentiation, intra cellular recognition, cell adhesion and tumorigenesis. Aim of the present study was to investigate the protective effect of andrographolide on cellular integrity by measuring the status of glycoconjugates in the buccal mucosa and plasma of hamsters during 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Oral squamous cell carcinoma was developed in the buccal pouch of hamsters by painting with DMBA three times a week for 14 weeks. The status of glycoconjugates was assayed in plasma and buccal mucosa using the specific calorimetric methods. We noticed 100% tumours formation with marked abnormalities in the status of plasma and buccal mucosa glycoconjugates in hamsters treated with DMBA alone. Oral administration of andrographolide at a dose of 50 mg/kg bw not only completely prevents the tumour formation, but also restored the status of glycoconjugates in DMBA treated hamsters. The present study thus demonstrates the protective effect of andrographolide on cell surface glycoconjugates abnormalities during DMBA-induced hamster buccal pouch carcinogenesis.
Journal of Medicinal Food, Dec 1, 2008
The aim of this study was to assess the chemopreventive efficacy of ferulic acid in 7,12-dimethyl... more The aim of this study was to assess the chemopreventive efficacy of ferulic acid in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. We induced oral squamous cell carcinoma in the buccal pouch of male Syrian golden hamsters by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. The tumor incidence, tumor volume, and tumor burden that were formed in the hamster buccal pouch were determined. The activities of carcinogen detoxification agents and status of lipid peroxidation and antioxidants were also estimated by specific colorimetric methods. We observed 100% tumor formation in DMBA-painted animals. The status of carcinogen-detoxifying agents, lipid peroxidation, and antioxidants was significantly disrupted in DMBA-painted animals. Oral administration of ferulic acid at a dose of 40 mg/kg of body weight to DMBA-painted animals on days alternate to DMBA painting for 14 weeks significantly prevented the tumor incidence, tumor volume, and tumor burden. Ferulic acid exhibited potent anti-lipid peroxidative effects as well as the ability to modulate the status of carcinogen-detoxifying agents and antioxidants in DMBA-painted animals. Our results demonstrate that ferulic acid has potent chemopreventive and antioxidant functions in DMBA-induced hamster buccal pouch carcinogenesis.
Pathology & Oncology Research, Dec 12, 2012
Nanochemoprevention has been introduced recently as a novel approach for improving phytochemicals... more Nanochemoprevention has been introduced recently as a novel approach for improving phytochemicals bioavailability and anti-tumor effect. The present study is designed to evaluate the chemopreventive efficacy of prepared naringenin-loaded nanoparticles (NARNPs) relative to efficacy of free naringenin (NAR) against 7,12-dimethyl benz(a)anthracene (DMBA)-induced oral carcinogenesis by evaluating the status of lipid peroxidation, antioxidants and immunoexpression patterns of proliferating cell nuclear antigen (PCNA) and p53 proteins. Transmission electron microscope (TEM) and dynamic light scattering (DLS) investigations have confirmed a narrow size distribution of the prepared nanoparticles (40-90 nm) with~88 % encapsulation efficiency. Oral squamous cell carcinoma (OSCC) was developed in the buccal pouch of golden Syrian hamsters by painting with 0.5 % DMBA in liquid paraffin three times a week for 14 weeks. DMBA painted animals revealed the morphological changes, hyperplasia, dysplasia and welldifferentiated squamous cell carcinoma. Moreover, the status of lipid peroxidation, antioxidants and immunoexpression of PCNA and p53 were significantly altered during DMBA-induced oral carcinogenesis. Oral administration of NARNPs (50 mg NAR/kg body weight/day) to DMBAtreated animals completely prevented the tumor formation as compared to the free NAR and significantly reduced the degree of histological lesions, in addition to restoration of the status of biochemical and molecular markers during oral carcinogenesis. In addition, NARNPs have more potent anti-lipid peroxidative, antiproliferative effect and antioxidant potentials compared to free NAR in DMBA-induced oral carcinogenesis. In conclusion, the present study suggests that NARNPs could be a potentially useful drug carrier system for targeted delivery of naringenin for cancer chemoprevention.
International Journal of Research in Pharmaceutical Sciences, Jul 15, 2013
The present study has investigated the protective effect of apigenin on 7, 12-dimethylbenz(a)anth... more The present study has investigated the protective effect of apigenin on 7, 12-dimethylbenz(a)anthracene (DMBA)-induced chromosomal abnormalities and DNA damage in the bone marrow cells of golden Syrian hamsters. The protective effect of apigenin was examined by analyzing the frequency of micronucleated polychromatic erythrocytes (MnPCEs), chromosomal aberrations and DNA damage in hamsters treated with DMBA. We noticed an increase in MnPCEs frequency, chromosomal aberrations and DNA damage in hamsters treated with DMBA alone. Oral pretreatment of apigenin for 5 days to DMBA-treated hamsters significantly decreased the frequency of MnPCEs, chromosomal aberrations and DNA damage. The present study thus suggests that apigenin has the ability to prevent 7, 12-dimethylbenz(a)anthracene–induced chromosomal abnormalities and DNA damage in the bone marrow cells of golden Syrian hamsters.
Objectives: To investigate the chemopreventive potential and antilipidperoxidative ef-Department ... more Objectives: To investigate the chemopreventive potential and antilipidperoxidative ef-Department of Biochemistry, fects of ethanolic root extract of Tephrosia purpurea (Linn.) Pers. (TpEt) on 7,12-Faculty of Science, dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch carcinoma. Annamalai University Materials and Methods: Oral squamous cell carcinoma was developed in the buccal Annamalainagar-608 002, pouch of Syrian golden hamsters, by painting with 0.5% DMBA in liquid paraffin, thrice a Tamil Nadu. India week, for 14 weeks. The tumor incidence, volume, and burden were determined. Oral administration of TpEt at a dose of 300 mg/kg, b.w., to DMBA (on alternate days for
PubMed, Sep 2, 2017
Objectives: Aim of the present study was to evaluate the in vitro cytotoxic potential of the dios... more Objectives: Aim of the present study was to evaluate the in vitro cytotoxic potential of the diosmin in A431 skin cancer cells. Materials and methods: The cytotoxic (anti-cell proliferative) potential of diosmin in A431 cells was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (cell viability), dual staining (apoptotic induction), dichloro-dihydro-fluorescein diacetate assay (reactive oxygen species [ROS] generation), DNA fragmentation study, Western blotting analysis (apoptotic markers expression) and flow cytometry (cell cycle arrest). Results: Diosmin reduced the cell viability of A431 cells in a dose-dependent fashion and the inhibitory concentration 50% value was attained at 45 μg/ml using MTT assay. Diosmin at a concentration of 45 μg/ml generated excessive ROS in A431 cells, as compared to untreated cells. Diosmin treated A431 cells also revealed multiple DNA fragments than the untreated cells. Diosmin upregulated the expression of p53, caspases 3 and 9 and downregulated the expression of Bcl-2, matrix metalloproteinases-2 and 9 in A431 cells. Conclusion: The cytotoxic or anti-cell proliferative potential of diosmin is due to its ROS-mediated apoptotic induction potential, as well as due to its role in the inhibition of invasion in the A431 cells.
Pakistan Journal of Biological Sciences, Mar 1, 2010
PubMed, Mar 1, 2012
The present study investigated the chemopreventive potential of geraniol, an acyclic monoterpene ... more The present study investigated the chemopreventive potential of geraniol, an acyclic monoterpene alcohol, by monitoring the tumor incidence and analyzing the status of phase II detoxification agents, lipid peroxidation by products and antioxidants in 7,12-dimethylbenz(a)anthracene (DMBA) induced mouse skin carcinogenesis. Skin tumor was developed by painting DMBA (25 microg in 0.1 ml acetone mouse(-1)) in the shaved back of the mice, twice weekly for 8 weeks. We noticed 100% skin tumor formation in mice treated with DMBA alone. The status of phase II detoxification agents and antioxidants were decreased where as lipid peroxidation by products were increased in tumor bearing mice. Oral administration of geraniol at a dose of 250 mg kg(-1) body weight significantly prevented the tumor formation as well as brought back the status of phase II detoxification agents, lipid peroxidation by products and antioxidants to near normal range in DMBAtreated mice. Present results suggest that geraniol might have inhibited abnormal cell proliferation occurring in skin carcinogenesis by modulating the activities of phase II detoxification agents and through its free radical scavenging potential.
PubMed, Aug 12, 2005
Purpose: Melatonin, the principle hormone of pineal gland plays an important role in several biol... more Purpose: Melatonin, the principle hormone of pineal gland plays an important role in several biological processes. The effects of melatonin on hepatic marker enzymes [aspartate and alanine transaminases (AST and ALT)], lipid peroxides [thiobarbituric acid reactive substances (TBARS)] and antioxidants [reduced glutathione (GSH), glutathione peroxidase (GPx) and glutathione-S-transferase (GST)] during N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis in rats were studied. Methods: Male albino Wistar rats of body weight 150-170 g were divided into four groups of six animals each. Group I animals served as control, Group II animals received single intraperitoneal injection of NDEA at a dose of 200 mg/kg body weight followed by weekly subcutaneous injections of CCl4 at a dose of 3 mL/kg body weight. Group III animals were treated as in Group II and melatonin (5 mg/kg body weight) was administered intraperitoneally. Group IV animals received melatonin alone at the same dose as Group III animals. Results: A significant increase in the activities of serum AST and ALT was observed in NDEA treated rats when compared with control animals. Melatonin administered rats showed a significant decrease in the activities of these enzymes when compared with NDEA treated animals. In the liver of NDEA-treated animals, decreased lipid peroxidation associated with enhanced antioxidant levels was observed. Administration of melatonin positively modulated these changes. Conclusion: Our results indicate that melatonin exerts chemopreventive effect by restoring the activities of hepatic marker enzymes and reversing the oxidant-antioxidant imbalance during NDEA-induced hepatocarcinogenesis.
Journal of Biochemical and Molecular Toxicology, Jul 1, 2008
The present study has investigated the antigenotoxic effect of withaferin-A, a steroidal lactone ... more The present study has investigated the antigenotoxic effect of withaferin-A, a steroidal lactone obtained from the roots and leaves of Withania somnifera, in 7,12-dimethylbenz(a)anthracene (DMBA)-induced genotoxicity. Measurement of the frequency of micronucleated polychromatic erythrocytes (MnPCEs) and chromosomal aberrations is used as cytogenetic endpoints. A single intraperitoneal injection of DMBA (30 mg/kg b.w.) to golden Syrian hamsters resulted in marked elevation in the frequency of MnPCEs and aberrations in the chromosomal structure. Hamsters pretreated with withaferin-A intraperitonealy 2 h before the injection of DMBA, significantly reduced the frequency of MnPCEs and chromosomal aberrations such as chromosomal break, gap, minute, and fragment. Our results thus demonstrated the antigenotoxic effect of withaferin-A in DMBA-induced genotoxicity in the bone marrow of golden Syrian hamsters.
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Environmental Toxicology and Pharmacology, Jul 1, 2009
The present study investigated the chemopreventive potential of geraniol, an acyclic monoterpene ... more The present study investigated the chemopreventive potential of geraniol, an acyclic monoterpene alcohol, by monitoring the tumor incidence and analyzing the status of phase II detoxification agents, lipid peroxidation by products and antioxidants in 7,12-dimethylbenz(a)anthracene (DMBA) induced mouse skin carcinogenesis. Skin tumor was developed by painting DMBA (25 µg in 0.1 ml acetone mouse-1) in the shaved back of the mice, twice weekly for 8 weeks. We noticed 100% skin tumor formation in mice treated with DMBA alone. The status of phase II detoxification agents and antioxidants were decreased where as lipid peroxidation by products were increased in tumor bearing mice. Oral administration of geraniol at a dose of 250 mg kg-1 body weight significantly prevented the tumor formation as well as brought back the status of phase II detoxification agents, lipid peroxidation by products and antioxidants to near normal range in DMBA treated mice. Present results suggest that geraniol might have inhibited abnormal cell proliferation occurring in skin carcinogenesis by modulating the activities of phase II detoxification agents and through its free radical scavenging potential.
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Papers by Shanmugam Manoharan