Genistein attenuates di‑(2‑ethylhexyl) phthalate-induced testicular injuries via activation of Nrf2/HO‑1 following prepubertal exposure.

Genistein attenuates di‑(2‑ethylhexyl) phthalate-induced testicular injuries via activation of Nrf2/HO‑1 following prepubertal exposure.
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Genistein 通过青春期前暴露后激活 Nrf2/HO1 来减轻邻苯二甲酸二(2乙基己基)酯引起的睾丸损伤。

DOI:
10.3892/ijmm.2018.3371
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发表时间:
2018-03
影响因子:
5.4
通讯作者:
Chong T
Chong T
中科院分区:
医学3区
文献类型:
--
作者:
Zhang L;Li H;Gao M;Zhang T;Wu Z;Wang Z;Chong T

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邻苯二甲酸二(2-乙基己基)酯(DEHP)和染料木素(GEN)是环境或饮食中最常见的内分泌干扰物(EDCs)。然而,在青春期前急性暴露于这两种内分泌干扰物的影响的调查一直缺乏。在本研究中,从PND 22至PND 35,通过灌胃给予青春期前雄性Sprague-Dawley大鼠DEHP和GEN,并给予溶剂对照、GEN 50 mg/kg体重(bw)/天、DEHP 50、150和450 mg/kg bw/天以及联合治疗。在PND 36时测定睾丸重量、肛门-生殖器距离和脏器系数等生殖参数。还研究了参与睾丸氧化还原状态调节的酶活性以及与抗氧化能力和凋亡相关的基因和蛋白质的表达。结果表明,到PND 36时,DEHP处理组大鼠睾丸重量、脏器系数、抗氧化酶活性显著降低,肾小管空泡化;然而,GEN联合给药部分减轻DEHP诱导的睾丸损伤,增强睾丸抗氧化酶活性,上调NF-E2相关因子2和血红素加氧酶-1的表达,这表明GEN在青春期前急性暴露于DEHP后通过抗氧化作用部分减轻了DEHP诱导的男性生殖系统损伤。因此,GEN可能用于减弱导致生殖障碍的其他EDCs的破坏性影响。
Di-(2-ethylhexyl) phthalate (DEHP) and genistein (GEN) are of the most common endocrine disrupting chemicals (EDCs) present in the environment or the diet. However, investigation of the effects of acute exposure to these two EDCs during prepuberty has been lacking. In this study, DEHP and GEN were administrated to prepubertal male Sprague-Dawley rats by gavage from PND22 to PND35 with vehicle control, GEN 50 mg/kg body weight (bw)/day, DEHP50, 150 and 450 mg/kg bw/day, and combined treatment. Reproductive parameters including testis weight, anogenital distance and organ coefficient were evaluated on PND36. Enzyme activity involved in the regulation of testicular redox state as well as expression of genes and proteins related to anti-oxidative ability and apoptosis were also investigated. The results revealed that by PND36, DEHP treatment had significantly decreased the testis weight, organ coefficient, testicular anti-oxidative enzyme activities and caused tubular vacuolation; however, co-administration of GEN partially alleviated DEHP-induced testicular injuries and enhanced testicular anti-oxidative enzyme activities and upregulated the expression of NF-E2 related factor 2 and heme oxygenase-1, which indicated that GEN partially attenuated DEHP-induced male reproductive system damage through anti-oxidative action following acute prepubertal exposure to DEHP. Thus, GEN may have use in attenuating the damaging effects of other EDCs that lead to reproductive disorders.
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