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经多剂量乙二醇单乙醚染毒后大鼠睾丸和精子的氧化损伤及血液毒性

Induction of oxidative damage in the testes and spermatozoa and hematotoxicity in rats exposed to multiple doses of ethylene glycol monoethyl ether.

机构信息

Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.

出版信息

Hum Exp Toxicol. 2010 Oct;29(10):801-12. doi: 10.1177/0960327109360115. Epub 2010 Feb 19.

DOI:10.1177/0960327109360115
PMID:20172899
Abstract

The effects of ethylene glycol monoethyl ether (EGEE) on the antioxidant systems of the testes and epididymal spermatozoa were investigated in rats at dose levels of 0, 100, 200 and 400 mg kg(-1) body weight (bw) administered orally by gavage for 14 consecutive days. The bw gain of the EGEE-treated rats decreased significantly at 200 and 400 mg kg(- 1) bw compared with the control group. There were no significant changes in the weights of the testes, epididymis, seminal vesicles and prostate glands of the EGEE-treated rats. In the testes, while EGEE treatment resulted in significant decrease in glutathione (GSH) level, superoxide dismutase (SOD) and catalase (CAT) activities, it markedly increased the malondialdehyde (MDA) level, glutathione-S-transferase (GST) and lactate dehydrogenase (LDH) activities at 200 and 400 mg kg(-1) dose levels but vitamin C content remained unaffected in all the groups. In the spermatozoa, administration of EGEE caused significant decrease in the activities of CAT, GST and LDH as well as in the levels of vitamin C and GSH but significantly increased the MDA level and SOD activity compared with the control rats. Histopathological examination showed severe degeneration of the testes, such as generalized erosion and necrosis of the germinal epithelium of the testes, but mildly affected the epididymis at 400 mg kg(-1) dose only. Data on spermatozoa analysis of EGEE-treated rats revealed significant decrease in the epididymal spermatozoa number, testicular spermatozoa number, daily spermatozoa production and spermatozoa motility but significantly increased the total spermatozoa abnormalities without affecting the spermatozoa live-dead ratio at all dose levels when compared with the control group. Results of haematological examination showed that white blood cells (WBC), platelets neutrophils and mean corpuscular haemoglobin concentration (MCHC) were significantly lower whereas lymphocytes were increased in 200 and 400 mg/kg EGEE-exposed rats than in the controls. EGEE at 100 mg/kg bw produced minor effect on haematological parameters but adversely affected testes and spermatozoa. In summary, short term administration of EGEE is hematotoxic and gonadotoxic and its effects on male reproduction could be due to the induction of oxidative stress in testes and spermatozoa.

摘要

乙二醇单乙醚(EGEE)对雄性大鼠睾丸和附睾精子抗氧化系统的影响,在经口灌胃给予 0、100、200 和 400mg/kg·bw 剂量连续 14 天的大鼠中进行了研究。与对照组相比,200 和 400mg/kg·bw 剂量的 EGEE 处理大鼠的体重增加明显减少。EGEE 处理大鼠的睾丸、附睾、精囊和前列腺重量无显著变化。在睾丸中,EGEE 处理导致谷胱甘肽(GSH)水平显著降低,超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性降低,丙二醛(MDA)水平、谷胱甘肽-S-转移酶(GST)和乳酸脱氢酶(LDH)活性显著升高,但各组维生素 C 含量均无变化。在精子中,EGEE 给药导致 CAT、GST 和 LDH 活性以及维生素 C 和 GSH 水平显著降低,但与对照组相比,MDA 水平和 SOD 活性显著升高。组织病理学检查显示,睾丸严重退化,如睾丸生精上皮普遍侵蚀和坏死,但仅在 400mg/kg·bw 剂量时轻度影响附睾。EGEE 处理大鼠的精子分析数据显示,附睾精子数、睾丸精子数、精子日产量和精子活力均显著降低,总精子异常率显著增加,但对精子活率无影响在所有剂量水平与对照组相比。血液学检查结果显示,白细胞(WBC)、血小板、中性粒细胞和平均红细胞血红蛋白浓度(MCHC)明显降低,而淋巴细胞在 200 和 400mg/kg·bw EGEE 暴露大鼠中增加与对照组相比。EGEE 在 100mg/kg·bw 时对血液学参数的影响较小,但对睾丸和精子有不良影响。总之,EGEE 的短期给药具有血液毒性和生殖毒性,其对雄性生殖的影响可能是由于睾丸和精子中氧化应激的诱导。

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