Phenotype of hepatic xenobiotic metabolizing enzymes and CYP450 isoforms of sanguinarine treated rats: Effect of P450 inducers on its toxicity

Abstract

Catalytic and immunochemical activities of cytochrome P450 (CYP) isoforms were investigated in argemone alkaloid, sanguinarine (SAN) intoxicated rats, pre-treated with different CYP inducers. SAN treated control (CON) and ethanol (ET), 3- methylcholantherene (MC) or dexamethasone (DEX) pre-exposed rats, resulted in 48, 64, 47 and 33% decrease in CYP content. SAN exposure to CON, and DEX, MC or ET pre-treated animals caused a decrease (22-37%) in glutathione-S-transferase (GST) activity, however, quinone reductase (QR) activity decreased (26–45%) in the MC pre-exposed group. Similarly, western-blot analysis of hepatic CYP1A1 and CYP1A2 showed a decrease (27–37%) in MC pre-treated SAN exposed animals. Further, a decrease in mortality in the SAN+MC (25%) group compared to SAN treated animals was also observed. The results suggest that inhibition of CYP 1A1, 1A2, 2D1, 2E1, 3A1, and Phase II enzymes by SAN augments its toxicity, whereas attenuation of SAN toxicity by MC may be due to removal of parent compound/metabolites from the body.

Keywords::

• Epidemic dropsy
• sanguinarine
• CYP inducers
• CYP expression phenotype
• Phase II enzymes
• metabolic toxicity

Acknowledgements

The authors are thankful to Director, IITR for his keen interest and assistance offered in carrying out this study. One of the authors (NPR) is thankful to the Council for Scientific and Industrial Research (CSIR), New Delhi for the award of Senior Research Fellowship. Financial assistance of CSIR Supra-institutional Project 08 is gratefully acknowledged. The manuscript is IITR communication # 2590.

Declaration of interest: The authors report no conflict of interests. The authors alone are responsible for the content and writing of the paper.