Dose and Time Dependent Protective Effects of Apocyanin and Curcumin Against Diclofenac-Induced Cardiotoxicity in Male Rats

Abstract

This study explored the protective potential of apocyanin and curcumin in diclofenac-induced cardiotoxicity utilizing cardiac enzymes, pro-inflammatory markers, and along with histopathological endpoints. A total of 123 male Wistar rats were used for the study. 43 rats were used for the determination of the median lethal dose (LD50) of apocyanin and curcumin while 80 rats were randomly divided into 8 groups of 10 rats each. Group 1(control) received distilled water while others received orally, per mg/kg body weight of treatments as follows: group 2(1000, apocyanin, group 3(1000, curcumin), group 4(10, diclofenac), group 5(500, apocyanin and 10, diclofenac), group 6(1000, apocyanin and 10, diclofenac), group 7(500, curcumin and 10, diclofenac) and group 8(1000, curcumin and 10, diclofenac). The treatments were administered daily for 14 and 28 days. LD50 up to 5000mg/kg body weight of apocyanin and curcumin did not show any fatality in animals. Administration of diclofenac significantly (p < 0.05) elevated the activities of creatinine kinase-MB, lactate dehydrogenase, levels of troponin-T, and tumor necrosis factor. There was no alteration in the activities of Interleukin- 1β. The histological results also showed cardiac insults such as cardiac muscle having severe fibro collagenous stroma, reduced myocytes density, and thick wall blood vessels. However, pretreatment with 500 and 1000 mg/kg body weight of apocyanin or curcumin attenuated all biochemical alterations and histological lesions induced by diclofenac in a dose-dependent manner.  Pretreatments with apocyanin and curcumin inhibitors of NADPH oxidases 2weres effective in ameliorating diclofenac-induced cardiotoxicity suppressing inflammation and restoring normal histological architecture, thus, highlighting the therapeutic potentials of apocyanin and curcumin in the management of diclofenac-mediated cardiotoxicity.