Effects of Carvacrol on Oxidative Stress and Fibrosis in Streptozotocin-Induced Diabetic Nephropathy: Histological, Gene Expression, and Biochemical Insights

Abstract

Diabetes mellitus (DM) leads to renal damage through oxidative stress. Carvacrol (CAR), a monoterpenoid phenol, possesses anti-inflammatory and antioxidant properties. We investigated the potential effects of CAR on histological, gene expression, and biochemical parameters in a rat model of DM. Four groups were created: group 1, control; group 2 (n = 9), DM; group 3 (n = 9), DM + dimethyl sulfoxide (DMSO); and group 4 (n = 9), DM + CAR. DM was created by injecting streptozotocin (STZ). CAR (20 mg/kg) was prepared through dissolution in 0.1% DMSO. CAR and 0.1% DMSO were administered daily for 4 weeks to groups 4 and 3, respectively. At the end of this study, urea, creatinine, paraoxonase-1 (PON-1), and arylesterase (ARES) were measured in serum samples. Histopathological changes and expression of Nuclear factor erythroid 2-related factor 2 (Nrf-2) in renal tissues were assessed. Immunohistochemical(ihc) staining and RT-qPCR analysis were performed to evaluate apoptosis, focusing on Bax and Bcl-2gene expression. Masson's trichrome(MT) staining and RT-qPCR analysis of COL1A1 and COL3A1 mRNA levels were used to assess fibrosis. Increased urea and creatinine levels in DM were significantly decreased after CAR administration. CAR application also improved reduced levels of PON 1 and ARES, which are associated with diabetes. Both immunohistochemistry and RT-qPCR analyses revealed that CAR therapy mitigated the diabetes-induced elevation in Bax and reduction in Bcl-2 expression. CAR treatment improved histopathological findings and renal Nrf-2 immunofluorescence(if) intensity. Furthermore, gene expression analysis demonstrated that COL1A1 and COL3A1 were upregulated in DM, while CAR administration downregulated them. In conclusion, CAR has a protective role in decreasing renal impairment linked to DM by regulating Bax and Bcl-2 levels and rectifying histological damage.