The present study was designated to assess oxidative damage and its effect on germ cell apoptosis in testes of streptozotocin (STZ)-induced diabetic rats. The role of antioxidant supplementation with a mixture of vitamins E and C and alpha lipoic acid for protection against such damage was also evaluated. Forty-five adult male rats were randomly divided into three groups: group I, control, non-diabetic rats; group II, STZ-induced, untreated diabetic rats; group III, STZ-induced diabetic rats supplemented with a mixture of vitamins E and C and alpha lipoic acid. Glycated hemoglobin (HbA(1C)), glucose, and insulin levels were estimated in blood samples. Malondialdehyde (MDA), the activities of the enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and caspase-3 in addition to testosterone (T) level were all determined in testicular tissues. Histopathological studies using H&E stain, as well as, immunohistochemical detection of apoptosis using (TUNEL) method were also performed. Blood glucose and HbA(1c) were significantly increased while insulin was significantly decreased in STZ-induced diabetic rats as compared with controls. In rat testicular tissues, MDA, and caspase-3 activity were significantly elevated while SOD and GPx enzymatic activities as well as T level were significantly decreased in diabetic rats as compared with control group. Antioxidant supplementation to diabetic rats restored the testicular enzymatic activities of SOD and GPx to almost control levels, in addition, MDA and caspase-3 activity decrease while T increase significantly as compared with untreated diabetic group. Prominent reduction of germ cell apoptosis was found in diabetic rats supplemented with antioxidants. An important role of testicular oxidative damage and germ cell apoptosis in diabetes-induced infertility could be suggested, treatment with antioxidants has a protective effect by restoring SOD and GPx antioxidant enzymatic activity.

The results suggest that activation of the oxytocin receptor (OTR) pathway by infusion of OT, OT analogs, or OT agonists may represent a promising approach for the treatment of diabetes and some of its complications, including diabetic osteopathy.

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