Taxifolin attenuates the developmental testicular toxicity induced by di-n-butyl phthalate in fetal male rats

被引：25
作者：
Li, Zengqiang [1 ,2 ]
Yu, Yige [1 ,2 ]
Li, Yang [1 ,2 ]
Ma, Feifei [1 ,2 ]
Fang, Yinghui [1 ,2 ]
Ni, Chaobo [1 ]
Wu, Keyang [1 ,2 ]
Pan, Peipei [1 ,2 ]
Ge, Ren-Shan [1 ,2 ]
机构：
[1] Wenzhou Med Univ, Affiliated Hosp 2, Dept Anesthesiol, Wenzhou 325027, Zhejiang, Peoples R China
[2] Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325027, Zhejiang, Peoples R China
来源：
FOOD AND CHEMICAL TOXICOLOGY | 2020年 / 142卷
关键词：
di-n-butyl phthalate; Taxifolin; Fetal Leydig cell; Testosterone; Fetal Leydig cell aggregation; Oxidative stress; IN-UTERO EXPOSURE; ACTIVATED PROTEIN-KINASE; LEYDIG-CELL AGGREGATION; AUTOSOMAL SEX REVERSAL; DI(N-BUTYL) PHTHALATE; OXIDATIVE STRESS; GENE-EXPRESSION; TESTIS; STEROIDOGENESIS; DYSGENESIS;
D O I：
10.1016/j.fct.2020.111482
中图分类号：
TS2 [食品工业];
学科分类号：
0832 ;
摘要：
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 (Cypllal), 17 beta-hydroxysteroid dehydrogenase 3 (Hsdl7b3), 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-1 alpha) 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.
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页数：12
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