PMID- 32525071 OWN - NLM STAT- MEDLINE DCOM- 20210329 LR - 20210329 IS - 1873-6351 (Electronic) IS - 0278-6915 (Linking) VI - 142 DP - 2020 Aug TI - Taxifolin attenuates the developmental testicular toxicity induced by di-n-butyl phthalate in fetal male rats. PG - 111482 LID - S0278-6915(20)30372-0 [pii] LID - 10.1016/j.fct.2020.111482 [doi] AB - Di-n-butyl phthalate (DBP) is widely used in consumer products as a plasticizer. Here, we report a natural product taxifolin that can attenuate developmental and reproductive toxicity of DBP. Pregnant rats were daily gavaged with 500 mg/kg DBP alone or together with taxifolin (10 and 20 mg/kg) from gestational day (GD) 12-21. At GD21, sera and testes of male fetus were collected. DBP significantly lowered serum testosterone level at 500 mg/kg and taxifolin can completely reverse its action. DBP caused abnormal aggregation of fetal Leydig cells and taxifolin can reverse it. DBP down-regulated the expression of the genes of cholesterol side-chain cleavage enzyme (Cyp11a1), 17beta-hydroxysteroid dehydrogenase 3 (Hsd17b3), and insulin-like 3 (Insl3) and taxifolin can reverse its action. DBP increased malondialdehyde levels and decreased superoxide dismutase and glutathione peroxidase expression and taxifolin can reverse it. DBP increased incidence of multinucleated gonocytes and taxifolin can prevent it. Moreover, DBP lowered sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha) and phosphorylated AMP-activated protein kinase (pAMPK) signalling and taxifolin antagonized DBP. In conclusion, in utero exposure to DBP caused developmental/reproductive toxicity of male offspring via increasing reactive oxygen species and taxifolin is an effective food component that completely reverses DBP-mediated action. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Li, Zengqiang AU - Li Z AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People's Republic of China. FAU - Yu, Yige AU - Yu Y AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People's Republic of China. FAU - Li, Yang AU - Li Y AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People's Republic of China. FAU - Ma, Feifei AU - Ma F AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People's Republic of China. FAU - Fang, Yinghui AU - Fang Y AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People's Republic of China. FAU - Ni, Chaobo AU - Ni C AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People's Republic of China. FAU - Wu, Keyang AU - Wu K AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People's Republic of China. FAU - Pan, Peipei AU - Pan P AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People's Republic of China. FAU - Ge, Ren-Shan AU - Ge RS AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People's Republic of China. Electronic address: r_ge@yahoo.com. LA - eng PT - Journal Article DEP - 20200607 PL - England TA - Food Chem Toxicol JT - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association JID - 8207483 RN - 0 (Antioxidants) RN - 0 (Plasticizers) RN - 2286E5R2KE (Dibutyl Phthalate) RN - 9IKM0I5T1E (Quercetin) RN - 9SOB9E3987 (taxifolin) SB - IM MH - Animals MH - Antioxidants/*pharmacology MH - Dibutyl Phthalate/*toxicity MH - Female MH - Male MH - Maternal Exposure MH - Plasticizers/*toxicity MH - Quercetin/*analogs & derivatives/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Testis/*drug effects/embryology OTO - NOTNLM OT - Fetal Leydig cell OT - Fetal Leydig cell aggregation OT - Oxidative stress OT - Taxifolin OT - Testosterone OT - di-n-butyl phthalate COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/06/12 06:00 MHDA- 2021/03/30 06:00 CRDT- 2020/06/12 06:00 PHST- 2019/12/21 00:00 [received] PHST- 2020/05/12 00:00 [revised] PHST- 2020/05/28 00:00 [accepted] PHST- 2020/06/12 06:00 [pubmed] PHST- 2021/03/30 06:00 [medline] PHST- 2020/06/12 06:00 [entrez] AID - S0278-6915(20)30372-0 [pii] AID - 10.1016/j.fct.2020.111482 [doi] PST - ppublish SO - Food Chem Toxicol. 2020 Aug;142:111482. doi: 10.1016/j.fct.2020.111482. Epub 2020 Jun 7.