Protective effects of nanostructures of hydrated C60 fullerene on reproductive function in streptozotocin-diabetic male rats
Protective effects of nanostructures of hydrated C60 fullerene on reproductive function in streptozotocin-diabetic male rats
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DOI：
10.1016/j.tox.2010.12.003
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发表时间：
2011-04-11
期刊：
影响因子：
4.5
通讯作者：
Naziroglu, Mustafa
中科院分区：
文献类型：
--
作者：
Bal, Ramazan;Turk, Gaffari;Naziroglu, Mustafa
糖尿病是男性性功能障碍和男性生育能力受损的公认原因。链脲佐菌素（STZ）用于胰腺的肿瘤性胰岛β细胞的医学治疗和1型糖尿病动物模型的产生，所述1型糖尿病的特征在于由于高血糖诱导的氧化应激和睾丸中的组织病理学改变而抑制生殖活性。寻找能够减轻糖尿病对生殖系统损害的药物是目前研究的重要领域。本研究旨在评估水合C-60富勒烯（C（60）HyFn），这是已知的强大的生物抗氧化剂，消除STZ糖尿病诱导的大鼠睾丸功能障碍。Wistar系雄性白化病大鼠分为4组：（1）对照组，（2）C（60）HyFn治疗非糖尿病组，（3）STZ糖尿病组和（4）C（60）HyFn治疗糖尿病组。一旦由STZ诱导高血糖症，第二和第四组中的大鼠以每天4 μ g/kg的剂量用C（60）HyFn（以饮用水的形式）治疗5周。糖尿病大鼠右侧附睾尾、精囊、前列腺、精子活动率和附睾精子密度的相对重量均明显低于对照组，而C（60）HyFn治疗组4的上述指标均得到恢复（p < 0.001）。苏木精-伊红染色显示，糖尿病大鼠睾丸出现明显的组织病理学改变，包括生殖细胞变性、脱屑、解体和减少，间质水肿和充血，但C（60）HyFn治疗可使组织病理学改变恢复，Johnsen睾丸评分显著增加（p < 0.001）。C（60）HyFn治疗恢复了STZ-糖尿病诱导的细胞凋亡增加。糖尿病大鼠血清睾酮、睾丸还原型谷胱甘肽（GSH）和α-生育酚水平显著降低，睾丸脂质过氧化水平显著升高（P < 0.001）。然而，用C（60）HyFn治疗糖尿病大鼠导致这些参数向对照水平的显著校正作用。C（60）HyFn单独应用对睾丸组织无任何毒性作用。此外。C（60）HyFn治疗糖尿病和非糖尿病大鼠导致一些重要的多不饱和脂肪酸的显着升高。总之，我们首次提出了大量证据表明，C（60）HyFn的管理显着减少糖尿病诱导的氧化应激和相关并发症，如睾丸功能障碍和生精障碍。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Diabetes mellitus is a well-recognized cause of male sexual dysfunction and impairments of male fertility. Streptozotocin (STZ) is used for medical treatment of neoplastic islet beta-cells of pancreas and producing of animal model of diabetes mellitus type 1 that is characterized by suppression of reproductive activity due to the hyperglycaemia-induced oxidative stress and histopathological alterations in testes. Seeking for the agents that could alleviate diabetes-induced damage to reproductive system is yet the important area of inquiry. The present study was designed to evaluate whether hydrated C-60 fullerene (C(60)HyFn), which is known to be powerful bioantioxidant, eliminate testicular dysfunction induced by STZ-diabetes in rats. Wistar strain male albino rats were divided into four groups of six animals each: (1) control group, (2) C(60)HyFn-treated nondiabetic group, (3) STZ-diabetic group and (4) C(60)HyFn-treated diabetic group. Once hyperglycaemia was induced by STZ, rats in the second and fourth groups were treated with C(60)HyFn (in the form of drinking water) at the dose of 4 mu g/kg daily for 5 weeks. In diabetic rats, relative weights of right cauda epididymis, seminal vesicles, prostate, sperm motility and epididymal sperm concentration were significantly less than those of control group, but which were restored in the fourth group treated with C(60)HyFn (p < 0.001). In hematoxylin and eosin staining, marked histopathological changes including degeneration, desquamation, disorganisation and reduction in germinal cells, interstitial oedema and congestion were evident in the testis of diabetic rats, but C(60)HyFn treatment resulted in recovery of histopathological changes and an increase in Johnsen's testicular score significantly (p < 0.001). C(60)HyFn treatment restores the increased apoptosis induced by STZ-diabetes. In diabetic rats, levels of serum testosterone, testicular reduced glutathione (GSH) and alpha-tocopherol were significantly reduced and testicular lipid peroxidation level was increased (p < 0.001). Nevertheless, treatment of diabetic rats with C(60)HyFn resulted in significant corrective effects on these parameters towards the control levels. C(60)HyFn, applied alone, did not exert any toxic effects in testicular tissues. Furthermore. C(60)HyFn treatment in diabetic and nondiabetic rats resulted in considerable elevations of some important polyunsaturated fatty acids. In conclusion, we have presented for the first time substantial evidence that administration of C(60)HyFn significantly reduces diabetes-induced oxidative stress and associated complications such as testicular dysfunction and spermatogenic disruption. (C) 2010 Elsevier Ireland Ltd. All rights reserved.