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Effects of nicotine on the testicular toxicity of streptozotocin-induced diabetic rat: Intervention of enalapril

机译:尼古丁对链脲佐菌素诱导的糖尿病大鼠睾丸毒性的影响:依那普利的干预

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The aim of the present study is to investigate whether nicotine augmented the testicular toxicity and angiotensin converting enzyme inhibitor, enalapril, can ameliorate the effects in diabetic rat. Male Sprague Dawley rats were randomized into five groups: control, nicotine, diabetic, Diab + Nico, and Diab + Nico + Enal. Animals were made diabetic by single injection of streptozotocin (55 mg/kg/intraperitoneally). Nicotine dissolved in drinking water at a concentration of 100 μg/ml was given ad libitum and enalapril was given orally at a dose of 10 mg/kg/day for four consecutive weeks. After 4 weeks of treatment, animals were killed and biochemical parameters glucose, glycosylated hemoglobin, cotinine, and the testosterone levels were measured. Testicular toxicity was evaluated using sperm count, sperm comet assay, histology, and immunohistochemical staining of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) and the proinflammatory markers (nuclear factor kappa B (NF-κB), cyclooxygenase (COX-2), and tissue necrotic factor alpha (TNF-α)) evaluated by western blotting. Results showed that nicotine did not alter the blood glucose and glycosylated hemoglobin level, significantly decreased the sperm count and increased the sperm DNA damage. These changes were accompanied by significant increases in the 8-oxo-dG, NF-κB, COX-2, and TNF-α expression. Furthermore, the intervention of enalapril in nicotine-treated diabetic rat attenuated the testicular damage and restored sperm count, sperm DNA damage, as well as reduced the expression of NF-κB, COX-2, and TNF-α. These findings clearly suggest that nicotine not only augmented the testicular toxicity in the diabetic rat but also increases the risk of germ cell toxicity effects that were attenuated by enalapril treatment.
机译:本研究的目的是研究尼古丁是否能增强睾丸毒性,而血管紧张素转化酶抑制剂依那普利可改善糖尿病大鼠的作用。将雄性Sprague Dawley大鼠随机分为五组:对照组,尼古丁,糖尿病,Diab + Nico和Diab + Nico + Enal。通过单次注射链脲佐菌素(55mg / kg /腹膜内)使动物患有糖尿病。连续四个星期随意给予溶解在饮用水中浓度为100μg/ ml的尼古丁,以10 mg / kg /天的剂量口服依那普利。治疗4周后,处死动物并测量葡萄糖,糖基化血红蛋白,可替宁和睾丸激素水平的生化参数。使用8-oxo-7,8-dihydro-2'-deoxyguanosine(8-oxo-dG)和促炎标记物(核因子κB(NF)的精子计数,精子彗星分析,组织学和免疫组化染色评估睾丸毒性-κB),环氧合酶(COX-2)和组织坏死因子α(TNF-α)通过western blotting评估。结果表明,尼古丁没有改变血糖和糖基化血红蛋白水平,显着降低了精子数量并增加了精子DNA损伤。这些变化伴随着8-oxo-dG,NF-κB,COX-2和TNF-α表达的显着增加。此外,依那普利在尼古丁治疗的糖尿病大鼠中的干预减轻了睾丸损伤并恢复了精子数量,精子DNA损伤,并降低了NF-κB,COX-2和TNF-α的表达。这些发现清楚地表明,尼古丁不仅增加了糖尿病大鼠的睾丸毒性,而且增加了依那普利治疗减弱的生殖细胞毒性作用的风险。

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