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 anti-inflammatory, 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. © 2025 Elsevier B.V., All rights reserved.