Resveratrol mitigates cadmium chloride-induced cardiotoxicity in rats via AMPK-mediated signaling: The modulatory role of low-dose gamma radiation

One of the dangerous consequences of exposure to the heavy metal cadmium (Cd) is cardiotoxicity. The cardiotoxic mechanism of Cd is linked to oxidative damage and inflammation. Trans-resveratrol (RES) had encouraging results in reducing inflammation and oxidative stress. In order to determine how RES and low doses of gamma radiation (LDR) affected cadmium-induced cardiotoxicity in an animal model, this study was designed. It found that RES had a modulatory influence on AMPK-mediated signaling pathways. Five equal groups of forty male albino rats were assigned: control, Cd, Cd+R, Cd+RES, and Cd+RES+R. Rats were given RES (50 mg/kg; for 35 days daily beginning from the second week of cadmium injection, i.p.) and Cd (2 mg/kg i.p.) five days a week for six weeks in a row. After that, they were given LDR (0.75 Gy). Histological and biochemical investigations were performed on the blood and heart samples. Along with a change in lipid profile characteristics, the Cd exposure increased the levels of cardiac damage indicators, creatine kinase-myocardial band (CK-MB), troponin I, and lactate dehydrogenase (LDH). In rat models subjected to Cd, we observed a significant downregulation of key metabolic and antioxidant regulators, including adenosine monophosphate activated protein kinase (AMPK), Sirtuin 1 (SIRT1), Nuclear factor erythroid 2-related factor 2 (NRF2), and Suppressor of cytokine signaling 3 (SOCS3). Conversely, there was a concomitant upregulation of pro-inflammatory and growth-related signaling pathways, as evidenced by increased levels of nuclear factor kappa-light-chain-enhancer of activated B cells NF-κB and mechanistic target of rapamycin (mTOR). However, heart biomarkers (CK-MB, LDH, troponin-1 and lipid profile TG, TC, LDL-C) improved when RES was administered either by itself or in conjunction with LDR. Additionally, the results of the biochemical studies were corroborated by the histological evaluations of cardiac tissues. According to our results, it can be concluded that Cd exposure causes significant cardiotoxicity by promoting oxidative damage and inflammation, disrupting key metabolic and antioxidant pathways. Resveratrol, either alone or combined with low-dose gamma radiation, effectively attenuates these adverse effects, improving cardiac function and tissue integrity. According to this study, a novel therapeutic possibility for the treatment of cardiotoxicity may be a combination of LDR and RES.