Effect of valproic acid treatment on penile structure in prepubertal rats.

ABSTRACT

INTRODUCTION: The aim of this study was to determine the histological effects of valproic acid (VPA) on the penis in prepubertal rats. METHODS: Twelve male Wistar rats (21-24 days old) were divided equally into 2 experimental groups, and given tap water (control group) or 300mg/kg/day VPA via gavage for 30 days. After the penes had been harvested, the antiangiogenic and antifibrogenic properties of VPA were evaluated immunohistochemically using vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), transforming growth factor-beta 1 (TGF-ß1) and Masson's trichrome staining. Apoptosis was determined by caspase-3 and caspase-9 immunoreactions. Results were expressed as histochemical score (HSCORE), a semi-quantitative analysis for the intensity of immunohistochemical reactivity. RESULTS: Immunohistochemical HSCORE decreased for VEGF and TGF-ß1 staining and increased for iNOS staining in rats treated with VPA compared with the control group. Intensities of caspase-3 and caspase-9 labeling were also significantly increased by administration of VPA. Masson's trichrome staining exhibited a fairly diminished level of collagen in the corpus cavernosum of rats treated with VPA. CONCLUSION: In the light of these results, the administration of VPA from prepuberty to adulthood led to increased apoptosis and deterioration of the smooth muscle/collagen ratio in rat's corpus cavernosum.