Abstract

Erectile dysfunction (ED) is one of the most common complications of diabetes, being oxidative stress an important feature of diabetic ED. Deleterious events induced by oxidative stress lead to crucial cellular and tissue alterations targeted by oxidative lesions. However, the noxious effects of oxidative stress mechanisms in penile tissue with the progression of diabetes, remains unclear. We intended to evaluate systemic and penile oxidative stress in an early and late stage of diabetes. Male Wistar rats were divided in groups: 2 and 8‐weeks of streptozotocin‐induced type 1 diabetes, and age‐matched controls. Systemic oxidative stress was evaluated in urine by hydrogen peroxide (H2 O2 ) quantification and in plasma by reduced/oxidized glutathione (GSH/GSSG) ratio. Penile oxidative status was assessed by H2 O2 production and by the evaluation of protein nitration through the detection of 3‐nitrotyrosine (3‐NT). 3‐NT was quantified by Western blotting analysis and immunohistochemistry allowed to identify its cavernosal cellular location. Systemic evaluation revealed a significant increase in urinary H2 O2 levels in both diabetic groups. A significant decrease of circulating GSH/GSSG ratio was observed in animals with late stage diabetes. In cavernosal tissue, H2 O2 production was significantly increased at 8‐weeks diabetes. Regarding 3‐NT cavernosal formation, data revealed a significant increment in advanced diabetes and a predominant location in cavernosal smooth muscle cells. We observed that systemic and cavernosal noxious effects induced by oxidative stress are predominant in advanced diabetes. Increased penile protein oxidative modifications in late‐staged diabetes may be responsible for structural/functional deregulations in cellular/molecular systems, contributing to the development of diabeticassociated ED.