AB178. Apocynin improves erectile function indiabetic rats through regulation of NADPH oxidase expression

Introduction: Diabetes is a risk factor for erectile dysfunction (ED). The proposed mechanisms responsible fordiabetic ED are associated with an increase in reactive oxygen species (ROS) production, over activity of RhoA/ROCK signaling pathway and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, as seen in experimental models of diabetic rats.

Aim: The aim of this study was to investigate whether NADPH oxidase inhibitor apocynin can ameliorate streptozotocin (STZ)-induced diabetes-related ED by reducing the ROS production and inhibiting the activity of RhoA/ROCK signaling pathway.

Methods: The diabetic rats were treated with and without the NADPH oxidase inhibitor apocynin.

Main outcome measures: Erectile responses were evaluated by determining mean arterial blood pressure (MAP) and intracavernosal pressure (ICP) with electrical stimulation of the cavernous nerve. Levels of mRNA expression were measured by real-time polymerase chain reaction (RT-PCR). Levels of protein expression were examined by Western Blot. ROS production was measured by dihydroethidium (DHE) staining and thiobarbituric acid reactive substances assay.

Results: The ratio of maximum ICP-to-MAP (max ICP/MAP) was significantly decreased in diabetic ED rats, compared to that of age-matched control rats (P<0.05). Apocynin improved erectile function of diabetic rats (P<0.05). Expression levels of RhoA (cytosol), nNOS and eNOS were reduced, compared to those of control rats (P<0.05). Apocynin significantly elevated their expression levels in diabetic rats (P<0.05). Expression levels of ROCK1, RhoA (membrane fraction), p-MYPT1 and NADPH oxidase subunits p47 (phox) and p67 (phox) were increased in diabetic rats when compared to those of control rats (P<0.05), and it was observed that apocynin significantly reduced their expression levels in diabetic rats (P<0.05). ROS production was increased in diabetic rats when compared to that of control rats (P<0.05), the effect of apocynin was a reduction in the ROS production in diabetic rats (P<0.05).

Keywords: Erectile dysfunction (ED); apocynin; nicotinamide adenine dinucleotide phosphate (NADPH) oxidase