Induction of cytochrome P450 3A1 expression by diallyl disulfide: protective effects against cyclophosphamide-induced
Sung-Hwan Kim1, In-Chul Lee2, Hyung-Seon Baek2
1College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea; Jeonbuk Department of Non-human Primate, Korea Institute of Toxicology, Jeonbuk 580-185, Republic of Korea.
Abstract:
The protective effects of diallyl disulfide (DADS) on cyclophosphamide (CP)-induced developmental toxicity and the possible mechanisms involved in this protection were investigated in rats. In order to study the mechanisms involved in the protection, we examined the effects of DADS on the expression of cytochrome P450 (CYP) 3A1 in the maternal liver and placenta and oxidative stress in the maternal hepatic tissues caused by CP. CP caused severe embryo-fetal developmental toxicity and hepatic oxidative stress. In contrast, DADS treatment significantly attenuated CP-induced developmental toxicity and oxidative damage in the maternal liver. DADS also significantly increased expression of CYP3A1 in the maternal liver and placenta. These results indicate that the protective effects of DADS against CP-induced developmental toxicity may be due to its ability to promote detoxification of CP, primarily by inducing CYP3A1 expression in the maternal liver and placenta, and its potent antioxidant effects.
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