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Background: Increase oxidative trauma is the main cause behind Cisplatin (CP) induced cardiotoxicity which restricts its clinical application as anti-neoplastic prescription. Acacia hydaspica is a natural shrub with diverse bioactivities. Acacia hydaspica ethyl acetate extract (AHE) ameliorated drug-induced cardiotoxicity in animals with anti-oxidative mechanisms. Current study aimed to evaluate the protective potential of A. hydaspica against cisplatin-induced myocardial injury. Methods: Rats were indiscriminately distributed into six groups (n= 6). Group 1: control; Groups 2: Injected with CP (7.5 mg/kg bw, ip, single dose) on day 16; Group 3: Treated for 21 days with AHE (400 mg/kg bw, oral); Group 4: Received CP injection on day 16 and treated with AHE for 5 days post injection; Group 5: Received AHE (400 mg/kg bw/day, po) for 21 days and CP (7.5 mg/kg bw, ip) on day 16; Group 6: Treated with silymarin (100 mg/kg bw, po) after 1 day interval for 21 days and CP injection (7.5 mg/kg bw, ip) on day 16. On 22nd day, the animals were sacrificed and their heart tissues were removed. Cisplatin induced cardiac toxicity and the influence of AHE were evaluated by examination of serum cardiac function markers, cardiac tissue antioxidant enzymes, oxidative stress markers and histology. Results: CP inoculation considerably altered cardiac function biomarkers in serum and diminished the antioxidant enzymes levels, while increased oxidative stress biomarkers in cardiac tissues AHE treatment attenuated CP-induced deteriorations in creatine kinase (CK), Creatine kinase isoenzymes MB (CK-MB), cardiac Troponin I (cTNI) and lactate dehydrogenase …