Effect of Carvacrol on Diabetes-Induced Oxidative Stress, Fibrosis and Apoptosis in Testicular Tissues of Adult Rats

Abstract

Diabetes mellitus (DM) is a chronic and widespread disease that negatively affects the male reproductive system. Carvacrol (CAR), a naturally occurring flavonoid in plants, exhibits various biological and pharmacological activities, including antiinflammatory, antioxidant, and anticancer properties. This study aimed to investigate the potential effects of CAR on testicular tissue damage induced by diabetes, which was modeled by Streptozotocin (STZ) administration. Thirty-two male Wistar albino rats were divided into four groups: Group 1: Control (n=8), Group 2: DM (n=8), Group 3: DM+DMSO (0.1 % dimethyl sulfoxide) (n=8), and Group 4: DM+CAR (20 mg/kg) (n=8). Diabetes was induced by a single intraperitoneal STZ injection (50 mg/kg). Histological changes were assessed using Hematoxylin-Eosin (H&E) staining and the Johnsen scoring system. Apoptosis was evaluated through immunohistochemical staining for the mitochondrial apoptosis markers Bax and Bcl-2, as well as RT-qPCR analysis of their gene expression levels. Fibrosis assessment involved Masson-Trichrome staining and RT-qPCR analysis of mRNA levels for the COL1A1 and COL3A1 genes. Additionally, Total Oxidant Status (TOS), Total Antioxidant Status (TAS), Oxidative Stress Index (OSI), and C-Reactive Protein (CRP) levels were measured in testicular tissue. CAR treatment significantly improved histological alterations associated with diabetes-induced testicular damage. DM was found to increase Bax levels while reducing Bcl-2 levels, whereas CAR reduced Bax levels and increased Bcl-2 gene and protein expression. TOS and OSI levels were elevated in the DM group, whereas TAS levels increased in the DM+CAR group. No significant differences in CRP levels were observed between the groups. These findings suggest that CAR may be effective in mitigating diabetes-induced testicular damage.