Resveratrol reverses cadmium chloride-induced testicular damage and subfertility by downregulating p53 and Bax and upregulating gonadotropins and Bcl-2 gene expression.

Resveratrol reverses cadmium chloride-induced testicular damage and subfertility by downregulating p53 and Bax and upregulating gonadotropins and Bcl-2 gene expression.
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DOI:
10.1262/jrd.2013-097
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发表时间:
2014-04-24
期刊:
The Journal of reproduction and development
影响因子:
--
通讯作者:
Khalil MA
Khalil MA
中科院分区:
其他
文献类型:
--
作者:
Eleawa SM;Alkhateeb MA;Alhashem FH;Bin-Jaliah I;Sakr HF;Elrefaey HM;Elkarib AO;Alessa RM;Haidara MA;Shatoor AS;Khalil MA

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本研究旨在探讨白藜芦醇(resveratrol, RES)对cdcl2致大鼠睾丸毒性的保护和治疗作用。将成年雄性大鼠设为A)对照组+NS, B)对照组+对照物(羟丙基环糊精生理盐水),C) RES处理组,D) CdCl2+NS, E) CdCl2+对照物,F) RES + CdCl2, M) CdCl2+ RES。实验结束时,测定各组血清FSH、LH和睾酮水平,测定睾丸TBARS水平和超氧化物歧化酶(SOD)活性。行附睾精液分析,RT-PCR检测睾丸Bcl-2、p53、Bax的表达。显微镜下观察睾丸组织病理变化。氯化镉前后给药RES可改善大鼠精液参数,包括精子数量、活力、每日精子产量和形态,提高血清促性腺激素和睾酮浓度,降低睾丸脂质过氧化,提高SOD活性。RES不仅可以减轻氯化镉引起的睾丸组织病理,而且可以防止氯化镉睾丸毒性的发生。氯化镉下调抗凋亡基因Bcl2的表达,上调促凋亡基因p53和Bax的表达。白藜芦醇通过上调Bcl2和下调p53和Bax基因表达来保护和部分逆转氯化镉睾丸毒性。RES具有抗氧化活性,可通过上调BCl2和下调p53和Bax表达部分逆转氯化镉睾丸毒性。
This study was performed to investigate the protective and therapeutic effects of resveratrol (RES) against CdCl2-induced toxicity in rat testes. Seven experimental groups of adult male rats were formulated as follows: A) controls+NS, B) control+vehicle (saline solution of hydroxypropyl cyclodextrin), C) RES treated, D) CdCl2+NS, E) CdCl2+vehicle, F) RES followed by CdCl2 and M) CdCl2 followed by RES. At the end of the protocol, serum levels of FSH, LH and testosterone were measured in all groups, and testicular levels of TBARS and superoxide dismutase (SOD) activity were measured. Epididymal semen analysis was performed, and testicular expression of Bcl-2, p53 and Bax was assessed by RT-PCR. Also, histopathological changes of the testes were examined microscopically. Administration of RES before or after cadmium chloride in rats improved semen parameters including count, motility, daily sperm production and morphology, increased serum concentrations of gonadotropins and testosterone, decreased testicular lipid peroxidation and increased SOD activity. RES not only attenuated cadmium chloride-induced testicular histopathology but was also able to protect against the onset of cadmium chloride testicular toxicity. Cadmium chloride downregulated the anti-apoptotic gene Bcl2 and upregulated the expression of pro-apoptotic genes p53 and Bax. Resveratrol protected against and partially reversed cadmium chloride testicular toxicity via upregulation of Bcl2 and downregulation of p53 and Bax gene expression. The antioxidant activity of RES protects against cadmium chloride testicular toxicity and partially reverses its effect via upregulation of BCl2 and downregulation of p53 and Bax expression.
DOI: 10.1016/s0378-4274(01)00483-0
发表时间: 2002-02-28
期刊: TOXICOLOGY LETTERS
影响因子: 3.5
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期刊: DRUGS
影响因子: 11.5
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发表时间: 2004-12-01
影响因子: 3.8
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