The effects of carvacrol on testicular apoptosis, inflammation, NRF2/HO-1 signaling pathway and spermatological parametersin experimentally induced diabetic rats.

Diabetes mellitus, which is common worldwide and causes many complications, also adversely affects the reproductive system in men. In order to reduce negative effects caused by diabetes in male reproductive system, the use of antioxidants is one of the most researched topics recently. In this study, it was aimed to investigate the effects of carvacrol on male reproductive system at fourth and eighth weeks of the experimental process in streptozotocin-induced diabetic male rats. For this purpose, 74 Wistar albino male rats were used. Rats were divided into 4 groups, 14 rats in the Control and Carvacrol Groups, 23 rats in the DM and DM + Carvacrol Groups. Groups; Group 1 (Control Group); (corn oil, gavage), Group 2 (DM Group); (STZ 55 mg/kg/single dose/i.p), Group 3 (Carvacrol Group); (Carvacrol 75 mg/kg/day/gavage), Group 4 (DM + Carvacrol Group); (STZ 55 mg/kg/single dose/i.p + Carvacrol 75 mg/kg/day/gavage). At the end of fourth week, 7 rats from the Control and Carvacrol groups and 10 rats from the DM and DM+Carvacrol groups were decapitated 24 hours after the last gavage application. The remaning rats were continued to be given carvacrol at the dose indicated by the administration of gavage. At the end of eighth week, the rats were decapitated 24 hours after the last gavage application. From the blood samples serum testosteron and glucose levels and testicular Malondialdehyde (MDA) levels, Glutathione (GSH) levels, Glutathione Peroxidase (GSH.Px), Catalase (CAT) enzyme activities; Nuclear Factor-Erythroid 2-Related Factor 2 (Nrf2), Heme Oxygenase-1 (HO-1), Nuclear Factor kappa B (NfkB), Cyclooxygenase-2 (COX-2), Bax and Bcl-2 protein expression levels; spermatological parameters (motility, epididimal spermatozoon density, abnormal spermatozoon ratio); reproductive organ weights (testis, epididymis, right cauda epididymis, vesicula seminalis, prostate) were evaluated. It was found that the body weight and serum testosterone level decreased (p<0,001) and serum glucose level increased (p<0,001) in the DM Groups at fourth and eighth weeks. It was found that in testicular tissue GSH (fourth week: p<0,001; eighth week: p<0,01) levels, Catalase (fourth week: p<0,01; eighth week: p<0,001) and GSH.Px activities, Nrf2, HO-1 and Bcl-2 protein expression levels decreased (p<0,001); MDA levels, NfkB, COX-2, Bax protein expression levels and Bax / Bcl-2 ratio increased (p<0,001) in the DM Groups at fourth and eighth weeks. It was found that motility (p<0,001), epididimal spermatozoon density (fourth week: p<0,05; eighth week: p<0,001) and reproductive organ weights (testis, epididymis, right cauda epididymis, vesicula seminalis, ventral prostate) reduced, abnormal spermatozoon rate (head, tail, total) increased (p<0,001) in the DM Groups. There was no difference in body weight, serum glucose and testosterone levels (p>0,05) in the DM+Carvacrol Group compared to the DM Group at fourth week. However it was determined that the body weight and serum testosterone level increased (p<0,001) and the glucose level decreased (p<0,001) in the DM+Carvacrol Group at eighth week. There was no difference in Catalase activities (p>0,05) in the DM+Carvacrol Groups compared to the DM Groups at fourth week; howewer it was determined to increase Catalase activities (p<0,001) in the DM+Carvacrol Group compared to the DM Group at eighth week. There was no difference in GSH levels (p>0,05) in the DM+Carvacrol Groups compared to the DM groups at fourth and eighth weeks. Howewer it was found that GSH.Px activities, Nrf2, HO-1 and Bcl-2 protein expression levels (p<0,001) increased in the DM+Carvacrol Groups compared to the DM groups at fourth and eighth weeks. Also it was found that MDA levels, NfkB, COX-2, Bax expression levels and Bax / Bcl-2 ratio (p<0,001) decreased in the DM+Carvacrol Groups compared to the DM groups at fourth and eighth weeks. There was no difference in spermatozoon motility and reproductive organ weight in the DM+Carvacrol Group compared to the DM Group at fourth week (p>0,05); however it was determined that spermatozoon motility (p<0,001) and reproductive organ weight were increased in the DM+Carvacrol Group compared to the DM Group at eighth week. It was determined that the density increased (fourth week: p<0,05; eighth week: p<0,001) and abnormal spermatozoon rate decreased (p<0,001) in the DM+Carvacrol Groups compared to the DM Groups at fourth and eighth week. In this study it was determined that decreased negative effects of diabetes on oxidative stress, apoptosis, inflammation and spermatological parameters in the diabetic rats by giving carvacrol of 75 mg/kg/day/gavage. As a result of this study; it was concluded that the negative effects of hyperglycemia in the male reproductive system can be prevented and/or reduced by giving carvacrol.