The possible therapeutic effects of vindoline on testicular and epididymal function in diabetes-induced oxidative stress male Wistar rats

Abstract

Diabetes mellitus is defined as a group of metabolic disorders characterised by chronic hyperglycaemia due to insufficient production and/or action of insulin and is regarded as one of the major sources of morbidity, mortality and economic burden to the modern society. A large body of scientific evidence support the fact that oxidative stress is elevated in diabetic conditions. Oxidative stress plays a significant role in the development of secondary complications of diabetes including diabetes-linked male sexual dysfunction. The management of sexual dysfunction as a secondary complication of diabetes relies on the management of the underlying diabetic condition. Glycaemic control and increased antioxidant protection are therefore necessary in the management of diabetes-induced oxidative stress male infertility. Pharmacological management of diabetes in form of various antihyperglycaemic, synthetic drugs has improved the outlook of diabetic patients; however, they are expensive, harbour unfavourable adverse effects and some have done little to prevent secondary complications of diabetes including diabetes-induced male sexual dysfunction. In addition to this, access to basic technologies for the management of diabetes mellitus and its secondary complications is still a challenge in low resource areas. Because of these challenges, there is a need to search for alternative remedies such as medication from natural products which are more affordable, well tolerated by the human body and are easily accessible. Medicinal plants are therefore viewed as an easily accessible and potent source of antioxidants capable of scavenging free radicals and fighting diabetes-induced oxidative stress. This study therefore investigated the effects of vindoline; an alkaloid extractable from Cantharanthus roseus in ameliorating diabetes-induced oxidative stress effects in testicular and epididymal tissues using male Wistar rats. Forty-eight (48), 6-week old male Wistar rats weighing between 190-230g with a conventional microbial status were divided into 6 groups, n=8, and used for this research project. Group 1 was the normal control, group 2 comprised non-diabetic rats treated with vindoline, and group 3 was the non-diabetic group of rats treated with glibenclamide- the standard drug for the treatment of diabetes. Group 4 was the diabetic control, group 5 comprised diabetic rats treated with vindoline and group 6 was the diabetic group of rats treated with glibenclamide. Diabetes was induced in group 4, group 5 and group 6 rats by subjecting them to 10% fructose water over a period of 2 weeks and thereafter, administering a single intraperitoneal injection of 40 mg/kg b.w streptozotocin (STZ). Fasting blood glucose levels were measured 72 hours after STZ injection and hyperglycaemia was confirmed where fasting blood glucose levels were more than 18mmol/l. The diabetic control (group 4) had higher fasting blood glucose levels, lower body weights as well as lower testicular and epididymal weights in comparison to the normal control (group 1). Additionally, the extent of lipid peroxidation in testicular and epididymal tissues of the diabetic control (group 4) was higher in comparison to that of the normal control (group 1). The diabetic control had lower testicular and epididymal antioxidant enzyme activities (superoxide dismutase and catalase) and lower oxygen radical absorption capacity (ORAC) in comparison to the normal control. Ferric reducing antioxidant power (FRAP) in testicular and epididymal tissues of the diabetic control (group 4) were not significantly different from those of the normal control (group 1). Treatment of diabetic rats with vindoline (group 5) for 5 weeks significantly reduced fasting blood glucose levels although the extent of reduction could not restore diabetic blood glucose levels to near-normal levels. Overall, treatment of diabetic rats with vindoline was able to minimise testicular oxidative stress as reflected by reduction in testicular malondialdehyde (MDA) levels. Furthermore, results of this study showed an increase in both testicular and epididymal catalase activities, an increase in epididymal SOD, an increase in testicular ORAC as well as an increase in both testicular and epididymal FRAP levels after 5 weeks of treating diabetic rats with vindoline (group 5). Epididymal lipid peroxidation levels, epididymal ORAC levels and testicular SOD levels of diabetic rats treated with vindoline (group 5) were however not significantly different from those of the diabetic control (group 4). Treatment of diabetic rats with vindoline or glibenclamide could not restore total body weights and testicular weights of group 5 and group 6 rats respectively, to near-normal levels. Furthermore, epididymal weights and testicular SOD activity of diabetic rats treated with vindoline (group 5) were not significantly different from those of the normal control (group 1). In conclusion, findings from this study demonstrated that treatment with vindoline could have protective effects against diabetes-induced oxidative stress in both testicular and epididymal tissues of male Wistar rats. Vindoline can therefore be considered a potential agent for the management of diabetes-induced oxidative stress male sexual dysfunction. Further studies with advanced technologies are however recommended to study the possible efficacy of vindoline in ameliorating diabetes-induced oxidative stress male sexual dysfunction. Furthermore, studies on the dose-dependent effects and long-term effects of vindoline administration on male reproductive function as well as the overall safety of treatment with vindoline are necessary.