Antioxidant Potential and Ability of Phloroglucinol to Decrease Formation of Advanced Glycation End Products Increase Efficacy of Sildenafil in Diabetes-Induced Sexual Dysfunction of Rats

INTRODUCTION: Diabetes-induced sexual dysfunction is associated with an increase in oxidative stress. Scavengers of reactive oxygen species (ROS) have been shown to reduce oxidative stress and aid in the management of sexual dysfunction in diabetes. AIM: The aim of the study was to test the hypothesis that antioxidant, which scavenge ROS and reduce formation of advanced glycation end products (AGEs), can potentiate efficacy of phosphodiesterase type 5 inhibitors in diabetes-induced sexual dysfunction that is associated with oxidative stress. MATERIALS AND METHODS: Effect of phloroglucinol and sildenafil on serum glucose level, sexual function, penile smooth muscle : collagen ratio, and phenylephrine precontracted corpus cavernosum smooth muscle (CCSM) was studied. The ability of phloroglucinol to reduce the formation of AGEs and its ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) was also evaluated. MAIN OUTCOME MEASURES: Antioxidant potential of phloroglucinol was studied in addition to its effect on diabetes-induced sexual dysfunction in presence and absence of sildenafil. RESULTS: Phloroglucinol (50 mg/kg, p.o.) significantly decreased serum glucose level and increased sexual function in streptozotocin-induced diabetic rats when compared with diabetic control rats. Sildenafil (5 mg/kg, p.o.) had no effect on glycemia but significantly increased sexual function of diabetic rats. Coadministration of phloroglucinol increased the efficacy of sildenafil by improving sexual function. Treatment of diabetic rats with phloroglucinol + sildenafil maintained smooth muscle : collagen levels similar to that of normal rat penile tissue. Phloroglucinol decreased formation of AGEs and significantly scavenged DPPH radical activity in vitro. Sildenafil relaxed isolated CCSM of normal rat and diabetic rat significantly, but phloroglucinol did not show any significant effect. Phloroglucinol also inhibited human CYP3A4 enzyme activity in vitro. CONCLUSION: Phloroglucinol coadministration increases efficacy of sildenafil in diabetes-induced sexual dysfunction. However, further studies are required to ascertain the benefits of phloroglucinol owing to its undesirable CYP3A4 inhibition activity.