Umbelliferone ameliorates oxidative stress and testicular injury, improves steroidogenesis and upregulates peroxisome proliferator-activated receptor gamma in type 2 diabetic rats.

Abstract

Diabetes mellitus (DM) is a chronic disease associated with serious complications, including male infertility. Umbelliferone (UMB) is a coumarin with promising antioxidant, anti-inflammatory and other beneficial effects. This study investigated the ameliorative effect of UMB against testicular injury, oxidative stress and altered steroidogenesis in rats with type 2 DM. Rats received a high fat diet for 4 weeks followed by a single injection of streptozotocin. Diabetic rats were treated with UMB or pioglitazone (PIO) for 6 weeks and samples were collected for analysis. Diabetic rats exhibited hyperglycemia, insulin resistance and dyslipidemia associated with increased serum pro-inflammatory cytokines, and decreased gonadotropins and testosterone. UMB significantly ameliorated metabolic alterations, decreased pro-inflammatory cytokines, and increased gonadotropins and testosterone levels. UMB prevented testicular injury, suppressed lipid peroxidation and nitric oxide and increased antioxidants in diabetic rats. In addition, UMB upregulated testicular gonadotropins receptors, steroidogenesis markers (steroidogenic acute regulatory protein, cytochrome P450 family 17 subfamily A member 1 [CYP17A1], 3β-hydroxysteroid dehydrogenase [3ß-HSD] and 17ß-hydroxysteroid dehydrogenase [17ß-HSD]), and peroxisome proliferator-activated receptor gamma (PPARγ) expression. UMB prevents testicular injury by preventing metabolic alterations, suppressing oxidative damage and inflammation, and boosting antioxidant defenses in diabetic rats. UMB enhanced pituitary-gonadal axis and steroidogenesis and upregulated testicular PPARγ in diabetic rats. Thus, UMB may represent a protective agent against testicular injury and sexual dysfunction associated with chronic hyperglycemia.