PMID- 35301062 OWN - NLM STAT- MEDLINE DCOM- 20220405 LR - 20220509 IS - 1873-1708 (Electronic) IS - 0890-6238 (Linking) VI - 109 DP - 2022 Apr TI - Prenatal ethanol exposure induces dynamic changes of expression and activity of hepatic cytochrome P450 isoforms in male rat offspring. PG - 101-108 LID - S0890-6238(22)00028-4 [pii] LID - 10.1016/j.reprotox.2022.03.002 [doi] AB - This study aimed at determining the effect of prenatal ethanol exposure (PEE) on the expression and activity of cytochrome P450 (CYP) isozymes at different life stages of male rat offspring. Pregnant Wistar rats were administered with ethanol (4 g/kg/d) intragastrically from gestational day (GD) 9-20. Male offspring's gene and activity of CYP isozymes were analyzed on GD 20 (only expression), postnatal day (PD) 84 and 196. Using aniline as probe, we compared the enzyme kinetics of hepatic CYP2E1 between two groups. Expression of CYP isozymes was examined in rat primary hepatocytes and human hepatic cell lines treated with ethanol or/and glucocorticoid. Gene level of Cyp1a2, 2b1, 2d1, 2e1, 3a1 and aryl hydrocarbon receptor were increased in PEE group on GD 20 and PD 84 and Cyp2e1 still exhibited an increasing trend on PD 196 compared with the control. PEE inhibited CYP2D1 and 2E1 activities in male offspring on PD 84. CYP activities in two groups became the same level on PD 196. PEE induced an opposite change in gene and protein level of hepatic CYP2E1 before and after birth. In consistent with lower protein level, aniline metabolism in PEE was weaker in liver microsome. Both single and combined use of ethanol or/and glucocorticoid increased CYPs expression in vitro. In conclusion, PEE programmed a higher gene and lower protein level of CYPs in male offspring, which dwindled with age. Impairment of protein levels and enzyme activities of CYPs may affect individual metabolism of endogenous and exogenous substances in early adulthood. CI - Copyright (c) 2022 Elsevier Inc. All rights reserved. FAU - Sun, Xiaoxiang AU - Sun X AD - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, Hubei Province, People's Republic of China; Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071, Hubei Province, People's Republic of China. FAU - He, Liang AU - He L AD - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, Hubei Province, People's Republic of China; Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071, Hubei Province, People's Republic of China. FAU - Bi, Huichang AU - Bi H AD - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangzhou Province, People's Republic of China. FAU - Huang, Min AU - Huang M AD - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangzhou Province, People's Republic of China. FAU - Xiang, E AU - Xiang E AD - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, Hubei Province, People's Republic of China; Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071, Hubei Province, People's Republic of China. FAU - Li, Xia AU - Li X AD - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, Hubei Province, People's Republic of China; Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071, Hubei Province, People's Republic of China. FAU - Wang, Hui AU - Wang H AD - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, Hubei Province, People's Republic of China; Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071, Hubei Province, People's Republic of China. Electronic address: wanghui19@whu.edu.cn. FAU - Guo, Yu AU - Guo Y AD - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, Hubei Province, People's Republic of China; Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071, Hubei Province, People's Republic of China. Electronic address: guoy@whu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220314 PL - United States TA - Reprod Toxicol JT - Reproductive toxicology (Elmsford, N.Y.) JID - 8803591 RN - 0 (Protein Isoforms) RN - 3K9958V90M (Ethanol) RN - 9035-51-2 (Cytochrome P-450 Enzyme System) SB - IM MH - Animals MH - *Cytochrome P-450 Enzyme System/genetics/metabolism MH - Ethanol/toxicity MH - Female MH - *Liver/metabolism MH - Male MH - Pregnancy MH - Protein Isoforms/metabolism/pharmacology MH - Rats MH - Rats, Wistar OTO - NOTNLM OT - CYP2E1 OT - Cytochrome P450 (CYP) OT - Drug metabolism OT - Male rat offspring OT - Prenatal ethanol exposure EDAT- 2022/03/19 06:00 MHDA- 2022/04/06 06:00 CRDT- 2022/03/18 05:39 PHST- 2021/06/27 00:00 [received] PHST- 2022/03/05 00:00 [revised] PHST- 2022/03/09 00:00 [accepted] PHST- 2022/03/19 06:00 [pubmed] PHST- 2022/04/06 06:00 [medline] PHST- 2022/03/18 05:39 [entrez] AID - S0890-6238(22)00028-4 [pii] AID - 10.1016/j.reprotox.2022.03.002 [doi] PST - ppublish SO - Reprod Toxicol. 2022 Apr;109:101-108. doi: 10.1016/j.reprotox.2022.03.002. Epub 2022 Mar 14.