Protective Role of Carvacrol Against Diclofenac-Induced Cardiotoxicity: Effects on Oxidative Stress, Apoptosis, Inflammation, ER Stress and Autophagy

Diclofenac (Diclo) is a widely used nonsteroidal anti-inflammatory drug (NSAID) for managing pain, inflammation, and joint disorders. However, studies have shown that diclofenac may induce cardiotoxicity via oxidative stress, inflammation, apoptosis, ER stress, and autophagy. Carvacrol (CRV), a natural monoterpenoid phenol, exhibits antioxidant, anti-inflammatory, and cytoprotective properties. This study aimed to evaluate the protective effects of carvacrol against diclofenac-induced cardiotoxicity by assessing relevant molecular and histological markers.MethodsIn the study, 35 Wistar rats were divided into 5 groups; Control, CRV, Diclo, Diclo + CRV25, and Diclo + CRV50. Diclo was administered intraperitoneally at a dose of 50 mg/kg. CRV (25 mg/kg and 50 mg/kg) was administered via oral gavage. Biochemical, molecular, and histological methods were used to investigate indicators of oxidative stress, inflammation, apoptosis, and ER stress damage in heart tissue.ResultsCRV treatment attenuated oxidative stress damage by reversing Diclo-induced changes: it significantly increased the levels of antioxidant markers (SOD, CAT, GPx, GSH) and decreased MDA levels, a marker of lipid peroxidation. CRV also reduced inflammatory mediators such as NF-kappa B and other pro-inflammatory cytokines. Furthermore, CRV downregulated apoptotic markers Bax and Caspase-3 while upregulating anti-apoptotic markers AKT-2 and Bcl-2. ER stress-associated proteins (ATF-6, PERK, IRE1, GRP-78) elevated by Diclo were also reduced by CRV. In addition, CRV alleviated structural and functional cardiac damage induced by Diclo.ConclusionOverall, CRV may be an effective treatment option for cardiac tissue damage caused by Diclo toxicity and may reduce the level of damage.