In the present study, we investigated the effect of allyl isothiocyanate (AITC) on liver detoxification signaling pathway in 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis. Mammary tumor was induced by a single dose of DMBA (25 mg/rat) injected subcutaneously near the mammary gland in Sprague-Dawley rats. DMBA-alone-treated rats show an increased synthesis of phase I detoxification enzymes, lipid peroxidative markers, liver marker enzymes, and lipid profiles whereas, depletion of phase II detoxification enzymes and antioxidants in rat liver tissues. Oral administration of AITC restored the levels of biochemical markers in DMBA-treated rats. Furthermore, histopathological results also confirmed that AITC protects DMBA-mediated hepatocellular damage. We also observed that AITC treatment significantly downregulates AhR and upregulates the expression of Nrf2 in DMBA-treated rats. The binding efficacy of AITC with AhR and Nrf2 analysis by molecular docking studies reveals that AITC has strong interaction with AhR and Nrf2 proteins through hydrogen and hydrophobic interactions. Thus, AITC prevents DMBA-induced mammary carcinogenesis via inhibition of phase I and induction of phase II detoxification enzymes by modulating AhR/Nrf2 signaling pathway.
Bisphenol-A (BPA) is a ubiquitous environmental chemical that produces adverse effect on reproduction system due to its potent estrogenic endocrine disruptive activity. The present study was aimed to investigate the monotonic dose effect of BPA on estrogen synthesis in female Sprague-Dawley rats. For this purpose, we administered three different doses of BPA (10, 50, 100 lg/ kg bw/day) into rats and analyzed various biochemical, hormonal, molecular and histological parameters. 10 lg BPA treated rats showed significantly decreased levels of phase I detoxification agents (CYP450, Cyt-b5). Overexpression of eNOS with decreased expression of StAR and steroidogenic enzymes (CYP11A1, aromatase) indicate decreased production of estrogen. Increased levels of serum gonadotropins (FSH, LH) and decreased levels of estradiol suggest mimetic action of BPA and its feedback inhibition. Increased body weight, lipid profile status of 10 lg BPA treated rats and histological analysis of ovary and mammary tissue support the study. Overall, our results suggest that BPA exerts its estrogen mimetic effects in a monotonic manner. Keywords Bisphenol-A Á Estrogen Á Ovary Á Mammary gland Abbreviation BPA Bisphenol-A TC Total cholesterol TG Triglycerides HDL-C High density lipoprotein-cholesterol TBARS Thiobarbituric acid substances GSH Reduced glutathione StAR Steroidogenic acute regulatory protein eNOS Endothelial nitric oxide synthase CYP11A1 Cytochrome P450 monooxygenase
The present study aimed to investigate the protective effect of allyl isothiocyanate (AITC) on glycoprotein components in 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. The levels of glycoprotein components such as hexose, hexosamine and sialic acid were analyzed colorimetrically in plasma, mammary and liver tissues. We observed an increased levels of glycoprotein components in plasma, mammary and liver tissues in cancer bearing rats. It was further confirmed by Periodic Acid Schiff staining in mammary and liver tissues. Upon oral administration of AITC to DMBA injected rats, the abnormal changes were reverted back to near normal levels and biochemical findings are supported by histological analysis. This could be due to the anti-neoplastic potential of AITC against DMBA-induced mammary carcinogenesis. The result shows that AITC has the potential to inhibit abnormal glycosylation that favors neoplastic transformation.
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