Department of Physiology, Faculty of Medicine, Firat University, 23119 Elazig, Turkey.
Toxicology. 2011 Apr 11;282(3):69-81. doi: 10.1016/j.tox.2010.12.003. Epub 2010 Dec 14.
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 β-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 4μg/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.
糖尿病是男性性功能障碍和男性生育力受损的公认原因。链脲佐菌素（STZ）用于治疗胰腺肿瘤胰岛β细胞，并产生 1 型糖尿病动物模型，其特征是由于高血糖引起的氧化应激和睾丸的组织病理学改变而抑制生殖活动。寻找可以减轻糖尿病对生殖系统损害的药物仍然是一个重要的研究领域。本研究旨在评估是否已知具有强大生物抗氧化作用的水合 C（60）富勒烯（C（60）HyFn）可以消除 STZ-糖尿病诱导的大鼠睾丸功能障碍。Wistar 品系雄性白化大鼠分为四组，每组 6 只：（1）对照组，（2）C（60）HyFn 处理的非糖尿病组，（3）STZ-糖尿病组和（4）C（60）HyFn 处理的糖尿病组。一旦 STZ 诱导高血糖，第二和第四组大鼠用 C（60）HyFn（以饮用水形式）以 4μg/kg 剂量每天处理 5 周。在糖尿病大鼠中，右侧附睾尾、精囊、前列腺、精子活力和附睾精子浓度的相对重量明显低于对照组，但用 C（60）HyFn 处理的第四组恢复（p<0.001）。在苏木精和伊红染色中，糖尿病大鼠睾丸组织明显可见组织病理学变化，包括退化、脱落、组织紊乱和生殖细胞减少、间质水肿和充血，但 C（60）HyFn 处理导致组织病理学变化恢复和 Johnsen 睾丸评分显著增加（p<0.001）。C（60）HyFn 处理可恢复 STZ-糖尿病诱导的增加的细胞凋亡。在糖尿病大鼠中，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升高（p<0.001）。然而，用 C（60）HyFn 治疗糖尿病大鼠可显著纠正这些参数向对照水平。C（60）HyFn 单独应用对睾丸组织没有任何毒性作用。此外，C（60）HyFn 处理糖尿病和非糖尿病大鼠可显著升高某些重要的多不饱和脂肪酸。总之，我们首次提供了大量证据，表明 C（60）HyFn 的给药可显著降低糖尿病引起的氧化应激以及睾丸功能障碍和生精障碍等相关并发症。
