Effects of nonyphenol exposure during pregnant and lactation period on expressions of CYP2E1 mRNA and protein of hepatic tissues in offspring rats / 重庆医学

ABSTRACT

Objective To investigate the effects of nonyphenol (NP)exposure during pregnant and lactation period on expression of cytochrome P450 2E1 (CYP2E1) mRNA and protein of hepatic tissues in offspring rats.Methods Pregnant rats were assigned to four groupsthe exposure groups received gavage with NP at dose levels of 50 mg · kg-1 · d-1 (low dose group),100 mg · kg-1 · d-1 (medium dose group),200 mg · kg-1 · d-1 (high dose group) and the control group was treated with corn oil alone,NP exposure time was limited from gestational day 6 to postnatal day 21.The newborn rats were sacrificed at 90 days after birth,followed by blood collection and serum separation.Then,serum biochemical indicators of liver function and lipid levels were detected.Glutathione peroxidase (GSH-PX),superoxide dismutase (SOD) activities,malondialdehyde (MDA) level and CYP2E1 mRNA and protein levels were determined in hepatic tissues.Pathologic changes in hepatic tissues were observed with HE staining.Results Compared with the control group,the aspartate aminotransferase (ALT),alanine aminotransferase (AST) levels and AST/ALT ratio of offspring rats in exposure groups were increased in a dose-dependent manner (P＜0.05),as well as serum TG,TC and LDL-C levels were increased (P＜0.05).The liver tissue structure of the control group was normal.The hepatic sinus of the medium dose group was showed mild expansion and inflammatory cellular infiltration.Otherwise,the liver of high dose group had a large amount of lipid droplets.Compared with the control group,SOD and GSH-PX activities were obviously decreased,while MDA level was significantly decreased in each exposure group (P＜0.05).CYP2E1 mRNA and protein expression levels of medium and high dose groups were higher than those in the control group (P＜0.05).Conclusion Exposure to NP during gestation and lactation period can induce lipid metabolism disorders and inflammatory lesions in hepatic tissues of offspring rats,and it maybe associated With up-regulation of CYP2E1 expression.