Dose-dependent adverse effects of salinomycin on male reproductive organs and fertility in mice.
Dose-dependent adverse effects of salinomycin on male reproductive organs and fertility in mice.
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盐霉素对雄性生殖器官和小鼠生育能力的剂量依赖性不良影响。
DOI：
10.1371/journal.pone.0069086
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Rath SK
中科院分区：
文献类型：
--
作者：
Ojo OO;Bhadauria S;Rath SK
盐霉素在畜牧业中用作抗生素。最近提出了其在癌症治疗中的意义。本文研究了盐霉素对雄性小鼠生殖系统的毒性作用。每天给予1、3或5 mg/kg盐霉素，持续28天。在最后一次处理24小时后处死一半小鼠，在停止处理28天后处死另一半小鼠。研究了SAL对体重和生殖器官重量的影响。沿着观察睾丸和附睾的组织结构及间质细胞的超微结构变化。血清和睾丸睾酮和黄体生成素的估计。测定超氧化物歧化酶、还原型谷胱甘肽、脂质过氧化反应、过氧化氢酶和乳酸脱氢酶活性。对精子计数、形态、活力和生育力进行了评价。Western blotting检测类固醇生成急性调节蛋白（星星）和细胞色素P450侧链裂解蛋白（CYP 11 A1）的表达模式。盐霉素处理对少数小鼠是致命的，并且以剂量依赖性方式延缓其他小鼠的身体生长，睾丸和精囊重量降低。睾丸生精小管断裂，附睾上皮细胞空泡化、坏死。间质细胞胞质肥大，核缩小，线粒体浓缩，内质网增生，脂滴增多。盐霉素可降低精子活力和精子数量，增加畸形精子数量，导致不育。高剂量组睾丸睾酮和黄体生成素水平降低，血清睾酮和黄体生成素水平升高。睾丸和附睾中超氧化物歧化酶和还原型谷胱甘肽的耗竭以及脂质过氧化反应的增加表明氧化应激的产生。星星和CYP 11 A1蛋白的抑制表达表明类固醇生成的抑制。然而，在盐霉素停药后28天，在睾丸中观察到精子发生。结果表明，盐霉素对雄性小鼠生殖系统具有可逆的剂量依赖性不良反应。
Salinomycin is used as an antibiotic in animal husbandry. Its implication in cancer therapy has recently been proposed. Present study evaluated the toxic effects of Salinomycin on male reproductive system of mice. Doses of 1, 3 or 5 mg/kg of Salinomycin were administered daily for 28 days. Half of the mice were sacrificed after 24 h of the last treatment and other half were sacrificed 28 days after withdrawal of treatment. Effects of SAL on body and reproductive organ weights were studied. Histoarchitecture of testis and epididymis was evaluated along with ultrastructural changes in Leydig cells. Serum and testicular testosterone and luteinizing hormones were estimated. Superoxide dismutase, reduced glutathione, lipid peroxidation, catalase and lactate dehydrogenase activities were measured. Spermatozoa count, morphology, motility and fertility were evaluated. Expression patterns of steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage proteins (CYP11A1) were assessed by Western blotting. Salinomycin treatment was lethal to few mice and retarded body growth in others with decreased weight of testes and seminal vesicles in a dose dependent manner. Seminiferous tubules in testes were disrupted and the epithelium of epididymis showed frequent occurrence of vacuolization and necrosis. Leydig cells showed hypertrophied cytoplasm with shrunken nuclei, condensed mitochondria, proliferated endoplasmic reticulum and increased number of lipid droplets. Salinomycin decreased motility and spermatozoa count with increased number of abnormal spermatozoa leading to infertility. The testosterone and luteinizing hormone levels were decreased in testis but increased in serum at higher doses. Depletion of superoxide dismutase and reduced glutathione with increased lipid peroxidation in both testis and epididymis indicated generation of oxidative stress. Suppressed expression of StAR and CYP11A1 proteins indicates inhibition of steroidogenesis. Spermatogenesis was however observed in testis 28 days after Salinomycin withdrawal. The results indicate reversible dose-dependent adverse effects of Salinomycin on male reproductive system of mice.
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影响因子：
64.5
作者：
Gupta PB;Onder TT;Jiang G;Tao K;Kuperwasser C;Weinberg RA;Lander ES
通讯作者：
Lander ES
影响因子：
3
作者：
Huczynski, Adam
通讯作者：
Huczynski, Adam
影响因子：
9
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影响因子：
0.6
作者：
Gava, A;Wouters, ATB;Barros, CSL
通讯作者：
Barros, CSL
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4.1
作者：
COOKE, BA;JANSZEN, FHA;VANDERMOLEN, HJ
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VANDERMOLEN, HJ