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

Abstract

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-β, 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-κB [NF-kB], tumor necrosis factor-α [TNF-α], and interleukin-1β [IL-1β]) 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-α, NF-kB, IL-1β, 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.