Abstract
Testicular injury is one of the most serious problems associated with diabetes mellitus. The present study aimed to compare the effects of two different doses of nobiletin and analyze its mechanisms of action against diabetes-induced testicular impairment in rats. Streptozotocin injection was used to induce diabetes. Diabetic rats received nobiletin orally at 10 or 25mg/kg daily for 30days. Diabetic rats displayed significant elevations in glucose, glycosylated hemoglobin (HbA1c), Homeostatic Model of Insulin Resistance (HOMA-IR), and pro-inflammatory cytokines, while the serum levels of insulin, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were significantly reduced. Histological changes to positivity for caspase-3 and decreased androgen receptors (AR) immunoexpression were observed in diabetic rats. Both doses of nobiletin improved hyperglycemia, reduced pro-inflammatory cytokines, and augmented insulin, testosterone, LH, and FSH levels. LH and FSH receptors and cytochrome P450 17 α-hydroxylase (CYP17A1) were markedly downregulated in terms of both gene and protein expression in testicular tissues of the diabetic group, effects that were markedly ameliorated with both doses of nobiletin. In addition, both doses significantly reduced lipid peroxidation and caspase-3 immunoexpression and improved the activity of the antioxidant enzymes and AR in testicular tissues of the diabetic group. Both nobiletin doses showed protective effects against diabetes-induced testicular injury by reducing oxidative stress, hyperglycemia, inflammation, and caspase-3 and upregulating the hypophysis-gonadal axis and AR. The high dose of nobiletin was more effective than the lower one.
Highlights
Diabetes mellitus, a common and serious metabolic syndrome, is one of the most important health problems affecting millions of people
Diabetic rats displayed a significant elevation in glucose, glycosylated hemoglobin (HbA1c), homeostasis model of insulin resistance (HOMAIR), and pro-inflammatory cytokines
Gene and protein manifestation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) receptors and cytochrome P450 17 α-hydroxylase (CYP17A1) was markedly down-regulated in testicular tissues of diabetic group, an effect which was markedly increased with both doses of nobiletin
Summary
A common and serious metabolic syndrome, is one of the most important health problems affecting millions of people. Increasing oxidative stress, in diabetic patients, leads to impaired testicular functions [3] probably by depletion of testosterone levels, spermatogenesis, seminal fluid volume and sperm count leading to male infertility [4]. Diabetes-induced oxidative stress can cause apoptosis [5]. Variation of hyperglycemia-induced oxidative stress illustrates an important plan for the handling of diabetes and its related testicular dysfunction. Testicular injury is one of the most serious problems of Diabetes mellitus. The present study aims to compare the effect of two different doses of nobiletin and the probable mechanisms against diabetes-induced testicular impairment in rats
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