The effects of alpha-lipoic acid on nitric oxide synthetase dispersion in penile function in streptozotocin-induced diabetic rats.

C Hurdag, H Ozkara, S Citci, I Uyaner, C Demirci
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Abstract

Diabetes-induced erectile dysfunction is one of the most prevalent complications of diabetes in males. alpha-Lipoic acid (ALA) and its reduced form, dihydrolipoic acid, are powerful antioxidants. Data strongly suggest that, because of its antioxidant properties, ALA is particularly suited to the prevention and/or treatment of diabetic complications that arise from overproduction of reactive oxygen and nitrogen. The aim of this study was to investigate the localization of nitric oxide synthetase (NOS) in normal and diabetic rat cavernous smooth muscles and to examine the effects of ALA on them. Rats were divided into four groups: control, diabetic, diabetic plus ALA, and ALA only. Penile tissues were taken 15 days after drug application and examined histochemically and immunohistochemically. Comparison of the control and diabetic groups revealed that the axons of nerve cells were not identified with Masson trichrome in the diabetic group, whereas in the control group NOS localization and immunostaining (endothelial NOS [eNOS]) were normal. Diabetic rats administered ALA showed improvement in Masson trichrome, nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) and eNOS localization compared with untreated diabetic rats. Although there was no difference between the control group and the group administered ALA only, we observed an increase in NADPH-d and eNOS. In erection, eNOS and neuronal NOS (nNOS) may have a significant role. In pathologic conditions, erectile dysfunction may occur as a result of an increase in inducible macrophage-type NOS (iNOS). ALA plays an important role in treatment of erectile dysfunction by decreasing iNOS and increasing other isoforms of NOS.

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硫辛酸对链脲佐菌素诱导的糖尿病大鼠阴茎功能中一氧化氮合成酶分散的影响。
糖尿病引起的勃起功能障碍是男性糖尿病最常见的并发症之一。α -硫辛酸(ALA)及其还原形式二氢硫辛酸是强效抗氧化剂。数据有力地表明,由于其抗氧化特性,ALA特别适合于预防和/或治疗由活性氧和活性氮过量产生的糖尿病并发症。本研究旨在探讨一氧化氮合成酶(NOS)在正常和糖尿病大鼠海绵状平滑肌中的定位及ALA对其的影响。将大鼠分为4组:对照组、糖尿病组、糖尿病+ ALA组和仅ALA组。给药15 d后取阴茎组织进行组织化学和免疫组织化学检查。对照组与糖尿病组比较,糖尿病组神经细胞轴突未见马松三色,而对照组NOS定位和免疫染色(内皮NOS [eNOS])正常。与未治疗的糖尿病大鼠相比,给予ALA的糖尿病大鼠在马尾松三色、烟酰胺腺嘌呤二核苷酸磷酸二磷酸二磷酸酶(NADPH-d)和eNOS定位方面均有改善。虽然对照组和只服用ALA的组之间没有差异,但我们观察到NADPH-d和eNOS的增加。在勃起过程中,eNOS和神经元NOS (nNOS)可能起重要作用。在病理条件下,勃起功能障碍可能是诱导型巨噬细胞型NOS (iNOS)增加的结果。ALA通过降低iNOS和增加NOS的其他亚型在治疗勃起功能障碍中起重要作用。
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