Unconjugated
INTRODUCTION:
Diabetes is a risk factor for erectile dysfunction (ED). The proposed mechanisms responsible for diabetic ED are associated with an increase in reactive oxygen species (ROS) production, overactivity 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 (MaxICP/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).
CONCLUSION:
NADPH oxidase inhibitor apocynin can ameliorate diabetes-related ED by reducing the ROS production and inhibiting the activity of RhoA/ROCK signaling pathway.
© 2012 International Society for Sexual Medicine.
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