RESUMEN
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.
RESUMEN
BACKGROUND: Diabetes induced sexual dysfunction is a leading cause of male sexual disorder and an early indicator of cardiovascular complication. Reactive oxygen species generated in body during diabetes is a main causative factor for erectile dysfunction, a sexual dysfunction. Adjuvant antioxidant therapy along with phosphodiesterases type 5 enzyme inhibitor (PDE5i) is more effective than PDE5i alone. OBJECTIVE: The aim of the study was to investigate efficacy of ellagic acid a known antioxidant and sildenafil in diabetes induced erectile dysfunction. MATERIALS AND METHODS: Type 1 diabetes was induced in male rats and rats were treated with ellagic acid (50 mg/kg, p.o.) and a combination of ellagic acid (50 mg/kg, p.o.) and sildenafil (5 mg/kg, p.o.), a PDE5i for 28 days. Sexual function was observed in diabetic rat and compared with those of treatment group and normal rats. Effect of ellagic acid was studied on advanced glycation end products (AGE) and isolated rat corpus cavernosum in vitro. RESULTS: Sexual function of diabetic rats was found to be reduced and ellegic acid treatment could preserve sexual function of diabetic rats to some extent. Ellagic acid + sildenafil treatment was more efficient in management of diabetes induced sexual dysfunction. Ellagic acid inhibited (AGE) in vitro implying its role in reducing oxidative stress in diabetes. The polyphenol could not increase sexual function in normal rats and relax isolated rat corpus cavernosum smooth muscle significantly. CONCLUSION: The study proves usefulness of adjuvant antioxidant therapy in the management of erectile dysfunction in diabetes.
