Pachaiappan Pugalendhi

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.

Dose response chemopreventive potential of allyl isothiocyanate against 7,12-dimethylbenz(a)anthracene induced mammary carcinogenesis in female Sprague-Dawley rats.

The present study aimed to investigate the dose response chemopreventive potential of allyl isothiocyanate (AITC) against 7,12-dimethylbenz(a)anthracene (DMBA) induced mammary carcinogenesis in female Sprague-Dawley rats. Mammary tumor was induced by a single dose of DMBA (25 mg/rat) injected subcutaneously near mammary gland. We observed reduced body weight and increased in total number of tumors, tumor incidence and tumor volume in DMBA-induced rats. We also observed decreased antioxidant status (SOD, CAT, GPX and GSH) and increased lipid peroxidation (TBARS and LOOH) in plasma and mammary tissues. Increased levels of CYP450, Cyt-b5 and decreased levels of phase II (GST and GR) biotransformation enzymes noticed in liver and mammary tissues of DMBA-induced rats. Further, increased levels of lipid profile (TC, TG, PL and FFA) and lipoprotein (LDL and VLDL) were noticed. Whereas, decreased level of HDL in plasma and decreased levels of PL and FFA in mammary tissue. Oral administration of AITC different doses (10, 20 and 40 mg/kg bw) inhibited the tumor incidence and restored levels of biochemical markers. Biochemical findings are supported by histopathological studies. These results suggested that AITC at a dose of 20 mg/kg bw significantly exert chemopreventive potential against DMBA-induced mammary carcinogenesis.

Antigenotoxic effect of genistein against 7,12-dimethylbenz[a]anthracene induced genotoxicity in bone marrow cells of female wistar rats

Carcinogen induced mutation in somatic cells leads to genetic instability, which is considered as an important facet of carcinogenesis. Agents that inhibit DNA adduct formation, stimulate DNA repair mechanisms, and possess antioxidant functions are considered as antigenotoxic agents. Genistein, the major isoflavone of soy products, protects animals against experimentally induced mammary and prostate cancers. 7,12-Dimethylbenz[a]anthracene (DMBA), a potent site-specific carcinogen, induce mutations in DNA through its active metabolite, dihydrodiol epoxide, what is a crucial step in cancer initiation. The antigenotoxic effect of genistein against DMBA-induced genotoxicity has been investigated in the present study by analyzing the frequency of micronucleated polychromatic erythrocytes (MnPCEs) and chromosomal aberrations as cytogenetic end-points. The status of lipid peroxidation, antioxidants and detoxication agents were used as biochemical end-points to assess the antigenotoxic effect of genistein. Elevated MnPCEs frequency, marked chromosomal aberrations and enhanced status of lipid peroxidation, antioxidants and detoxication agents were observed in DMBA-treated animals. Oral pretreatment of genistein (20 mg/kg b.w.) for 5 days to DMBA-treated animals significantly reduced the frequency of micronucleus formation and chromosomal abnormalities as well as reversed the status of biochemical variables. Our results suggest that genistein has potent antigenotoxic effect against DMBA-induced genotoxicity.

Protective Effect of 3, 3-Diindolylmethaneon Bisphenol A Activated GPR30, RAS,PI3K/Akt Estrogenic Signaling Pathway inFemale Sprague-Dawley Rats

The present study was aimed to evaluate the protective effect of 3, 3-diindolylmethane (DIM) on bisphenol A (BPA) induced estrogen signaling in the mammary glands of female Sprague-Dawley rats. Chronic administration of BPA (10 μg/kg/bw) to rats exerts rapid estrogenic action via GPR30 and activate cascade of signaling molecule which induce cell proliferation in the mammary gland. Western blot analysis of mammary tissues shows over expression of GPR30, SRC, RAS, PI3K and Akt proteins and immunohistochemical analysis reveals over expression of PCNA and no significant changes in ERs. Further, oral administration of DIM (5 mg/kg/bw), alternative days to BPA treated rats for the period of 12 weeks show significant decrease in the expression pattern of GPR30, SRC, RAS, PI3K, Akt and PCNA. The results of our study demonstrate that BPA induces rapid action via the over expression of proteins in non-genomic estrogen signaling pathway. Administration of DIM inhibits the action of BPA by modulating the expression of proteins involved in GPR30 cascade signaling pathway mediated cell proliferation in mammary glands of female rats.