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二烯丙基二硫化物诱导细胞色素P450 3A1表达:对环磷酰胺诱导的胚胎-胎儿发育毒性的保护作用。

Induction of cytochrome P450 3A1 expression by diallyl disulfide: protective effects against cyclophosphamide-induced embryo-fetal developmental toxicity.

作者信息

Kim Sung-Hwan, Lee In-Chul, Baek Hyung-Seon, Moon Changjong, Kim Sung-Ho, Yoo Jin Cheol, Shin In-Sik, Kim Jong-Choon

机构信息

College 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.

College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.

出版信息

Food Chem Toxicol. 2014 Jul;69:312-9. doi: 10.1016/j.fct.2014.04.024. Epub 2014 Apr 22.

DOI:10.1016/j.fct.2014.04.024
PMID:24769015
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.

摘要

研究了二烯丙基二硫化物(DADS)对环磷酰胺(CP)诱导的大鼠发育毒性的保护作用及其可能的保护机制。为了研究其保护机制,我们检测了DADS对孕鼠肝脏和胎盘细胞色素P450(CYP)3A1表达以及CP所致孕鼠肝组织氧化应激的影响。CP可导致严重的胚胎-胎儿发育毒性和肝脏氧化应激。相比之下,DADS处理可显著减轻CP诱导的发育毒性和孕鼠肝脏的氧化损伤。DADS还可显著增加孕鼠肝脏和胎盘CYP3A1的表达。这些结果表明,DADS对CP诱导的发育毒性的保护作用可能归因于其促进CP解毒的能力,主要是通过诱导孕鼠肝脏和胎盘CYP3A1的表达,以及其强大的抗氧化作用。

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