Capsaicin ameliorates myocardial injury in diabetic rats via upregulating Nrf-2, HO-1 and iNOS tissue concentrations besides normalizing the distribution of structural proteins desmin and α-SMA

Myocardial injury remains the leading cause of morbidity and mortality in diabetic patients. On the other hand, scientists have noticed that capsaicin has a distinctive pharmacological effect on the cardiovascular system. Hence, the present study aimed to investigate the potential ameliorative effects of capsaicin on the development of myocardial injury in diabetic rats and to identify the underlying mechanisms. Forty-eight animals were divided into four groups: control, diabetic, diabetic + rosuvastatin, and diabetic + capsaicin. Capsaicin was found to have a significant hypoglycemic and hypolipidemic effect compared to the other diabetic groups. Capsaicin also significantly increased the levels of the antioxidant enzymes catalase, superoxide dismutase, and glutathione peroxidase, as well as reduced glutathione. This was likely due to the upregulation of the cytoplasmic content of its key regulators Nrf-2 and HO-1, as found by immunostaining and western blot analysis. Additionally, capsaicin significantly increased the levels of cardioprotective nitric oxide, which could be stimulated by the upregulation of iNOS. Capsaicin also had a significant anti-inflammatory effect by reducing the high levels of TNF-α and IL-1β. Capsaicin was able to significantly inhibit myocardial structural damage, as found by histopathological examination using Hematoxylin and eosin (H&E), Masson trichrome, and immunostaining of desmin and α-smooth actin. This was further confirmed on the biochemical level by the attenuation of cardiac enzymes, MDA, carbonyl content, and heat shock proteins (HSP) 70 upregulation. Finally, capsaicin was able to attenuate myocardial injury by decreasing the myocardial concentration of the apoptotic protein cleaved caspase-3. In conclusion, this study has introduced capsaicin as a promising naturally derived agent that can attenuate the development of myocardial damage in diabetics through its hypoglycemic, hypolipidemic, antioxidant, anti-inflammatory, and anti-apoptotic effects.