Nagarethinam Baskaran

Chemopreventive potential of ferulic acid in 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis in Sprague–Dawley rats

Aim of the present study was to investigate the chemopreventive potential of ferulic acid on 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary carcinogenesis in Sprague-Dawley rats. The chemopreventive potential of ferulic acid was assessed by monitoring the tumor incidence, as well as analyzing the status of biochemical (enzymatic and non-enzymatic antioxidants and phase II detoxification enzymes) and molecular (p53 and bcl-2) markers during DMBA-induced mammary carcinogenesis. Mammary carcinogenesis was induced in Sprague-Dawley rats by providing a single subcutaneous injection of 25 mg of DMBA in 1 ml emulsion of sunflower oil (0.75 ml) and physiological saline (0.25 ml) to each rat. Oral administration of ferulic acid at a dose of 40 mg/kg body weight to rats treated with DMBA significantly prevented the tumor formation in 80% of animals (8/10). Also, oral administration of ferulic acid significantly protected the biochemical and molecular abnormalities in DMBA treated rats. Although the exact mechanism for the chemopreventive potential of ferulic acid in DMBA-induced mammary carcinogenesis is unclear, its antigenotoxic and antioxidant potential as well as modulatory effect on phase II detoxification cascade could play a possible role.

Chemopreventive potential of apigenin in 7,12-dimethylbenz(a)anthracene induced experimental oral carcinogenesis.

Aim was to investigate the chemopreventive potential of apigenin by analyzing the tumor incidence as well as monitoring lipid peroxidation, antioxidants and phase I and phase II detoxification as biomarkers during DMBA induced hamster buccal pouch carcinogenesis. Oral tumors were developed in the buccal pouches of golden Syrian hamsters using topical application of 0.5% DMBA (DMBA) three times a week for 14weeks. Tumor incidence, tumor volume and burden were measured in hamsters treated with 7,12-dimethylbenz(a)anthracene and DMBA+apigenin (2.5mg/kg body weight) treated hamsters. Oral administration of apigenin not only completely prevented the formation of oral tumors, it also brought back the status of lipid peroxidation, antioxidants and phase I and phase II detoxification agents to near normal range during DMBA induced oral carcinogenesis. The present study thus concludes that apigenin might have inhibited oral carcinogenesis by improving the status of antioxidant defense mechanism and modulated the activities of phase I and phase II detoxification cascade toward increased excretion of active metabolite of DMBA, during DMBA induced hamster buccal pouch carcinogenesis.

Anti-tumor initiating potential of andrographolide in 7,12-dimethylbenz[a]anthracene induced hamster buccal pouch carcinogenesis.

The aim of the study was to investigate the chemopreventive potential of andrographolide in 7,12-dimethylbenz(a) anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Oral tumors developed in the buccal pouch of golden Syrian hamsters at a 100% incidence on painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. Marked abnormalities in the status of detoxification enzymes, lipid perxodiation and antioxidants were noticed in hamsters treated with DMBA alone. Oral administration of andrographolide at a dose of 50 mg/ kg bw to hamsters treated with DMBA not only completely prevented the tumor formation but also restored the status of the above mentioned biomarkers. The present study thus demonstrates the chemopreventive potential of andrographolide in DMBA-induced hamster buccal pouch carcinogenesis, which is probably due to its antioxidant potential as well as modulating effect on xenobiotic metabolising enzymes during DMBA-induced oral carcinogenesis.

Anti-Cell Proliferative Efficacy of Ferulic Acid Against 7, 12-dimethylbenz(a) Anthracene Induced Hamster Buccal Pouch Carcinogenesis

The present study was designed to explore the anti-cell proliferative efficacy of ferulic acid by analysing the expression pattern of cell proliferative markers, proliferating cellular nuclear antigen (PCNA) and cyclin D1, in the buccal mucosa of golden Syrian hamsters treated with 7,12-dimethylbenz(a)anthracene (DMBA). Oral squamous cell carcinomas developed in the buccal pouch of hamsters using topical application of 0.5% DMBA three times a week for 14 weeks. Immunohistochemical (PCNA) and RT-PCR (Cyclin D1) analysis revealed over expression of PCNA and cyclin D1 in the buccal mucosa of hamsters treated with DMBA alone (tumor bearing hamsters). Oral administration of ferulic acid at a dose of 40 mg/kg bw to hamsters treated with DMBA not only completely prevented the tumor formation but also down regulated the expression of PCNA and cyclin D1. The results of the present study thus suggests that ferulic acid might have inhibited tumor formation in the buccal mucosa of hamsters treated with DMBA through its anti-cell proliferative potential as evidenced by decreased expression of PCNA and cyclin D1.

Modulating effect of lupeol on the expression pattern of apoptotic markers in 7, 12-dimethylbenz(a)anthracene induced oral carcinogenesis.

Apoptosis, also known as cell suicide or programmed cell death, removes unwanted and genetically damaged cells from the body. Evasion of apoptosis is one of the major characteristic features of rapidly proliferating tumor cells. Chemopreventive agents inhibit or suppress tumor formation through apoptotic induction in target tissues. The aim of the present study was to investigate the pro-apoptotic potential of lupeol during 7,12-dimethylbenz(a) anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Topical application of 0.5% DMBA three times a week for 14 weeks in the buccal pouches of golden Syrian hamsters resulted in oral squamous cell carcinoma. The expression pattern of apoptotic markers was analyzed using immunohistochemistry (p53, Bcl-2, Bax) and ELISA reader (caspase 3 and 9). In the present study, 100% tumor formation with defects in apoptotic markerexpression pattern was noticed in hamsters treated with DMBA alone. Oral administration of lupeol at a dose of 50 mg/kg bw completely prevented the formation oral tumors as well as decreased the expression p53 and Bcl-2, while increasing the expression of Bax and the activities of caspase 3 and 9. The present study thus indicated that lupeol might inhibit DMBA-induced oral tumor formation through its pro-apoptotic potential in golden Syrian hamsters.

Coumarin protects 7,12-dimethylbenz(a)anthracene-induced genotoxicity in the bone marrow cells of golden Syrian hamsters

Aim : Aim of the present study was to evaluate the antigenotoxic effect of coumarin by measuring the frequencies of micronuclei and the degree of DNA damage in the bone marrow cells of hamster treated with 7,12-dimethylbenz(a)anthracene (DMBA). Materials and Methods: Genotoxicity was induced in experimental hamsters by single intraperitoneal injection of DMBA (30 mg/kg b.w.). The frequency of micronucleated polychromatic erythrocytes (MnPCEs) and DNA damage were assessed in the bone marrow cells of experimental hamsters. The status of lipid peroxidation, antioxidants and phase I and II detoxification agents were utilized as biochemical end points to assess the dose-dependent antigenotoxic potential of coumarin in DMBA-induced genotoxicity. Results: Increase in micronuclei frequency was accompanied by increase in tail length, percent of tail DNA, tail movement and olive tail movement in the bone marrow cells of hamsters treated with DMBA alone. A significant increase in the levels of thiobarbituric acid reactive substances, antioxidants and phase I and II detoxification agents were also noticed in hamsters treated with DMBA alone. Oral pretreatment of coumarin at a dose of 100 mg/kg b.w to hamsters treated with DMBA significantly decreased the frequency of MnPCEs and DNA damage in the bone marrow cells. Also, coumarin restored the status of biochemical variables in the plasma and liver of hamsters treated with DMBA. Conclusions: Present study demonstrated the antigenotoxic effect of coumarin in DMBA-induced genotoxicity. The antigenotoxic potential of coumarin is probably due to its antioxidant potential and modulating effect on detoxification cascade during DMBA-induced genotoxicity.

Chemopreventive Potential of Coumarin in 7, 12-dimethylbenz(a) anthracene Induced Hamster Buccal Pouch Carcinogenesis

The aim of the present study was to investigate the chemopreventive effect of coumarin against 7, 12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis by monitoring tumor incidence and histopathological changes as well as by analyzing the status of biochemical markers (lipid peroxidation, enzymatic and non-enzymatic antioxidants, phase I and phase II detoxification enzymes). Oral squamous cell carcinomas were induced in the buccal pouch of Syrian golden hamsters by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. We noted 100% tumor formation with marked abnormalities in the biomarkers status in hamsters treated with DMBA alone. Oral administration of coumarin at a dose of 100 mg/kg body weight (bw) to DMBA treated hamsters completely prevented the tumor formation as well as restored the status of biochemical variables. The results of the present study thus suggest that the chemopreventive effect of coumarin is probably due to its anti-lipid peroxidative potential and modulating effect on carcinogen detoxification agents in favor of the excretion of ultimate carcinogenic metabolites of DMBA during DMBA-induced hamster buccal pouch carcinogenesis.

Antihyperglycemic effect of Coscinium fenestratum and Catharanthus roseus in alloxan-induced diabetic rats

Introduction : Diabetes mellitus, the life-threatening endocrine disorder, affects 170 million people worldwide every year. Statistical projections about India suggest that 57 million Indians will be affected by diabetes mellitus by the year 2025, making the country with highest number of diabetics in the world. Alloxan-induced diabetes mellitus in experimental animals is commonly used to evaluate the antidiabetic effect of medicinal plants and their constituents. The present study has investigated the antidiabetic efficacy of ethanolic extract of Coscinium fenestratum stem and Catharanthus roseus leaves in alloxan-induced diabetic rats. Materials and Methods: Diabetes mellitus was induced in overnight fasted (>8 hours) Wistar rats by single intraperitoneal injection of freshly prepared alloxan monohydrate (150 mg/kg bw) solution in physiological saline. The mechanistic pathway for the antidiabetic potential of these plants was evaluated by analyzing the status of glucose, insulin, C-peptide, glycosylated hemoglobin, activities of carbohydrate-metabolizing enzymes, and glycogen content. The antidiabetic effect of these plant products was also compared with the standard reference drug, glibenclamide. Results: The study revealed that the ethanolic extract of C. fenestratum stem and C. roseus leaves have potent antidiabetic efficacy in alloxan-induced diabetic rats. The antidiabetic efficacy was also much comparable with that of glibenclamide. Conclusions: The present study concludes that the ethanolic extract of C. fenestratum stem and C. roseus leaves have potent antihyperglycemic effect in alloxan-induced diabetic rats. C. fenestratum and C. roseus could therefore be used as an alternative remedy for diabetes mellitus and its complications.

WITHDRAWN: Apigenin: A potent antigenotoxic and anticlastogenic agent

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Protective effect of 18β-glycyrrhetinic acid on cell surface glycoconjugates abnormalities in 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis

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 well-developed 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.