Exercise ameliorates stanozolol and cannabis co-abuse testicular damage in rats evidenced by biochemical and histological regulation of SIRT1 and STS

Polydrug use among teenagers is widespread and emergent either among athletes or non-athletes. It is reported that stanzolol (Stanz) is commonly abused with cannabis (Cann), this combination probably affects the testicular functions negatively. Aim The present study aimed to evaluate the toxic effects of Stanz and or Cann on reproductive hormones and testicular enzymes. Male Wistar rats were administered Stanz (5 mg/kg, s.c., once per week) and Cann (20 mg/kg, i.p., daily) either alone or in combination for two months, in exercise or sedentary conditions. Swimming exercise protocol was applied. Administration of both Stanz and Cann induced testicular damage, as evidenced by altered hormones, oxidative stress, and testicular enzymes. The testis tissue was significantly injured by the combined administration. In serum, levels of free testosterone, follicular stimulating hormone (FSH), lutenizing hormone (LH) were markedly reduced, while sorbitol dehydrogenase level increased. Moreover, tissue malondialdehyde (MDA) was significantly increased, glutathione (GSH) content decreased, testicular N-acetyl-β-glucosaminidase (NAG) and Myeloperoxidase (MPO) were increased. SIRT1 and STS mRNA expression were downregulated. Besides, distinct histopathological changes were detected in testis of Stanz and Cann injected rats. Nevertheless, Stanz, Cann or combined treatment showed a considerable up-regulation of immunoexpression of inducible nitric oxide synthase (iNOS) and caspase-3 in testes tissue. Oxidative stress and inflammation played a significant role in the observed pathological changes. Training was partially ameliorating for the observed effects. Use of the drugs in sedentary rats had more detrimental effects on testes. Although exercise could palliate the damage partially, it was not fully protective.