Catalytic characteristics of CYP3A22-dependent mequindox detoxification

Abstract

The anti-bacterial agent mequindox is widely used as an animal feed additive in China. Its potential effect on host cells, however, remains largely unknown. Here, we report that pig CYP3A22 represents an important metabolic enzyme in mequindox catalysis. Interestingly, we found that ectopic expression of CYP3A22 reversed the mequindox-induced G2 cell cycle accumulation in cultured pig hepatocytes. To further probe the catalytic mechanism of CYP3A22 in mequindox metabolism, we identified 2′-acetyl-hydroxylation as a major catalytic step of CYP3A22-dependent mequindox metabolism using LC-MS/MS spectrometry. Together, our study suggests that CYP3A22 plays an important role in mequindox metabolism via 2′-acetyl-hydroxylation. © 2010 Elsevier B.V. All rights reserved.link_to_subscribed_fulltex