Antioxidative, Anti-inflammatory and Cardioprotective Effects of Nauclea orientalis Bark Extract on Doxorubicin Induced Oxidative­stress.

Abstract

Clinical utility of doxorubicin, the effective antineoplastic agent, is limited due to cumulative and dose-dependent free radical-induced cardiotoxicity. Nauclea orientalis (Bak mee) bark has strong antioxidant potential. Therefore, the objective of this study was to investigate the mechanism of action of Nauclea aqueous bark extract against doxorubicin-induced oxidative-stress in Wistar rats. Rats were divided into five groups of 10 animals in each. Group 1: normal control; group 2: plant extract control; group 3 received 2.0g/kg lyophilized plant extract for 14 days, 18mg/kg doxorubicin on 11th day; group 4 received l0mL/kg dH2O for 14 days, 18mg/kg doxorubicin on 11th day; group 5: positive control: lOmL/kg dH2O, 14 days, 180mg/kg dexrazoxane, 0.Sh before doxorubicin18mg/kg. Animals were sacrificed on day 15; blood was drawn and heart tissues were collected separately for the estimation of antioxidant parameters and for the histopathological assessment. Diagnostic markers of myocardial damage were analyzed on serum and oxidative stress markers were analyzed on homogenates of heart tissues. Cardiac troponin 1 (cTnl) level in doxorubicin control group was 145.15pg/mL and pre-treatment with Nauclea bark extract showed a significant reduction (p<0.05) of cTnl (38.92pg/mL). Rest of the cardiac markers; NT-proBNP, AST, and LDH also showed significantly increased (p<0.05) values in the Doxorubicin control group compared to the control. Plant treated group showed a significant reduction in (p<0.05) these parameters compared to the doxorubicin control. Total antioxidant level in the doxorubicin control group (2.92mmol/L) showed a significant reduction (p<0.05) compared to the normal control group (5.52mmol/L) and co-treatment with plant extract showed a significant increase (3.28mmol/L) compared to the doxorubicin control. A significant reduction (p<0.05) was observed in reduced glutathione, glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase activity in rats treated with doxorubicin and pre-treatment with plant extract showed a significant increase (p<0.05) in all these parameters compared to the doxorubicin control. A significant increase (p<0.05) in lipid peroxidation and myeloperoxidase activity were observed in doxorubicin control (2.05nmol/µL, 285.32AAU/mL respectively) compared to the normal control (1.19nmol/µL, 157.74AAU/mL respectively). Plant treated group showed a significant decrease (p<0.05) in lipid peroxidation (1.63nmol/µL) and myeloperoxidase activity (225.22AAU/mL). The doxorubicin­treated group showed histological evidence of extensive damage to the myocardium while the plant-treated group showed preserved myocardium with a lesser degree of damage. Therefore, It can be concluded that Nauclea aqueous bark extract has the potential to significantly reduce doxorubicin-induced oxidative-stress in Wistar rats.