Effects of Nrf-۲/HO-۱, NF-κB/Cox-۲/TLR-۴, and Bax/Bcl-۲/caspase-۳ pathways in alleviating azithromycin-induced cardiotoxicity in rats: Potential cardioprotective role of crocin

Objective(s): This study aimed to investigate the potential protective effects of crocin against azithromycin (AZ)-induced cardiotoxicity.Materials and Methods: The experimental design consisted of four groups: Control, crocin, Azithromycin, and crocin plus Azithromycin (AZ+CR ۵۰). To evaluate oxidative stress, inflammation, and apoptosis in cardiac tissue, a combination of biochemical, molecular, and histological techniques was employed. Biomarkers such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), nuclear factor erythroid ۲–related factor ۲ (Nrf-۲), and heme oxygenase-۱ (HO-۱) were assessed to determine anti-oxidant status, while malondialdehyde (MDA) and advanced oxidation protein products (AOPP) were measured as indicators of oxidative damage. Protein levels of inflammatory markers NF-κB and toll-like receptor ۴ (TLR-۴) and apoptotic regulators Bax, Bcl-۲, and Caspase-۳ were quantified.Results: Crocin treatment effectively attenuated AZ-induced oxidative stress by enhancing anti-oxidant enzyme activity and reducing MDA and AOPP levels. Furthermore, crocin significantly down-regulated the expression of NF-κB and TLR-۴ proteins, indicating reduced inflammation. The proapoptotic proteins Bax and Caspase-۳, which were elevated following AZ exposure, were markedly decreased by crocin co-treatment. Conversely, the reduced expression of the antiapoptotic protein Bcl-۲ caused by AZ was restored by crocin. In addition, AZ administration led to increased levels of COX-۲ and MAPK-۳, both of which were down-regulated following crocin treatment. Histological analysis revealed that crocin reduced degenerative and necrotic changes in heart tissue caused by AZ.Conclusion: These findings suggest that crocin exerts cardioprotective effects against AZ-induced damage by modulating oxidative stress, inflammation, and apoptosis.

کلیدواژه ها:

Apoptosis ، Azithromycin ، Cardiotoxicity ، Crocin ، Inflammation ، Oxidative stress