Nimbolide prevents myocardial damage by regulating cardiac biomarkers, antioxidant level, and apoptosis signaling against doxorubicin-induced cardiotoxicity in rats

The current work planned to assess the protecting properties of nimbolide against doxorubicin (DOX)-treated myocardial damage. Myocardial damage was produced with 2.5 mg/kg of DOX given on alternative days (14 days). Thiobarbituric acid reactive substances (TBARS) levels of a lipid peroxidative marker were elevated, whereas reduced body weight, heart weight, blood pressure indices and reduced levels of antioxidants like glutathione-S-transferase, superoxide dismutase, catalase, glutathione peroxidase, glutathione, and glutathione reductase were observed in the heart tissue of DOX-treated animals. DOX-treated animals showed augmented levels of cardiac markers likes monocyte chemotactic protein-1, interferon-gamma, aspartate transferase, creatine kinase, lactate dehydrogenase, creatine kinase-muscle/brain, heart-type fatty acid-binding protein, glycogen phosphorylase isoenzyme BB, transforming growth factor-beta, brain natriuretic peptide, myoglobin, and cTnI in serum. Histopathological assessment confirmed the DOX-induced cardiotoxicity. Furthermore, DOX-induced rats showed augmented inflammatory mediators (nuclear factor-kappa B [NF-kB], tumor necrosis factor-alpha [TNF-alpha], and interleukin-1 beta [IL-1 beta]) and increased PI3K/Akt signaling proteins (PI3K, p-Bad/Bad, caspase-3, and p-Akt), whereas decreased oxidative markers (HO-1 and NQO-1) and p-PTEN were observed. Nimbolide-supplemented rats showed reduced activity/levels of cardiac markers and TBARS levels in serum and heart tissue. Levels of enzymatic and nonenzymatic antioxidants were augmented in the heart tissue of nimbolide-supplemented rats. Nimbolide influence decreased apoptosis, inflammation, and enhanced antioxidant markers through the modulation of p-Bad/Bad, caspase-3, PI3K, p-Akt, TNF-alpha, NF-kB, IL-1 beta, HO-1, NQO-1, and p-PTEN markers. The histopathological explanations were observed to be in line with biochemical analysis. Therefore, the finding of current work was that nimbolide has a defensive effect on the myocardium against DOX-induced cardiac tissue damage.