Therapeutic role of resveratrol treatment on inflammation and oxidative stress-mediated renal and cardiac dysfunction in isoproterenol (ISO) administered ovariectomized female Long Evans rats

This study aimed to evaluate the protective effects of resveratrol on renal and cardiac dysfunction in isoproterenol (ISO) administered ovariectomized female Long Evans rats. ISO was administered at 50 mg/kg (twice weekly) to induce infarct-like symptoms, while resveratrol was given daily at 100 mg/kg for two weeks. All animals received a standard chow diet and water ad libitum. The echocardiography was done on day 14 for all rats to acquire functional data. On day 15, rats were sacrificed, and plasma and tissue samples were collected for analysis. Various markers, including malondialdehyde (MDA), nitric oxide (NO), advanced oxidation protein products (AOPP), catalase, superoxide dismutase (SOD), glutathione (GSH), creatinine kinase - muscle brain (CK-MB), myeloperoxidase (MPO), creatinine, and uric acid, were assessed. This investigation revealed that ISO impaired antioxidant defenses, while resveratrol treatment helped restore redox balance and prevented cardiac and renal injury. Resveratrol treatment preserved the ejection fraction (EF%), fractional shortening (FS%), and lowered cardiac mass in ISO-administered rats. Gene expression analysis revealed that ISO downregulated key antioxidant mediators, while upregulating the pro-inflammatory genes. Resveratrol reversed these effects, suggesting reduced oxidative stress and inflammation. The histopathological analysis supported the protective role of resveratrol, showing reduced tissue damage and collagen deposition in heart and kidney tissues. Moreover, network pharmacology analysis showed potential interactions with key molecular pathways for resveratrol. In conclusion, resveratrol mitigated ISO-induced cardiac and renal damage by enhancing antioxidant defenses and suppressing inflammation, suggesting its potential clinical application in preventing or treating oxidative stress-related cardiovascular and renal disorders.