Abstract
BackgroundIncrease 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.MethodsRats were indiscriminately distributed into six groups (n = 6). Group 1: control; Groups 2: Injected with CP (7.5 mg/kg bw, i.p, single dose) on day 16; Group 3: Treated for 21 days with AHE (400 mg/kg b.w, 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 b.w/day, p.o.) for 21 days and CP (7.5 mg/kg b.w., i.p.) on day 16; Group 6: Treated with silymarin (100 mg/kg b.w., p.o.) after 1 day interval for 21 days and CP injection (7.5 mg/kg b.w., i.p.) 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.ResultsCP 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 (LDH) levels and ameliorated cardiac oxidative stress markers as evidenced by decreasing lipid peroxidation, H2O2 and NO content along with augmentation in phase I and phase II antioxidant enzymes. Additionally, CP inoculation also induced morphological alterations which were ameliorated by AHE. In pretreatment group more significant protection was observed compared to post-treatment group indicating preventive potential of AHE. The protective potency of AHE was comparable to silymarin.ConclusionResults demonstrate that AHE attenuated CP induce cardiotoxicity. The polyphenolic metabolites and antioxidant properties of AHE might be responsible for its protective influence.
Highlights
Increase oxidative trauma is the main cause behind Cisplatin (CP) induced cardiotoxicity which restricts its clinical application as anti-neoplastic prescription
Effect on heart and body weight CP treatment showed insignificant difference in heart weight/body weight (HW/Body weight (BW)) ratio compared to control rats, while noteworthy reduction in body weight was noticed in CP alone or in CP + Acacia hydaspica ethyl acetate fraction (AHE) groups compared to control rats
Nitroc oxide (No) significant deviations in the BW gain or Heart weight (HW)/BW ratio were observed in rats treated with AHE alone
Summary
Increase oxidative trauma is the main cause behind Cisplatin (CP) induced cardiotoxicity which restricts its clinical application as anti-neoplastic prescription. Acacia hydaspica ethyl acetate extract (AHE) ameliorated drug-induced cardiotoxicity in animals with anti-oxidative mechanisms. Clinical implication of Cisplatin (cis-dichlorodiammineplatinum (II), CP) is restricted owing to augmented oxidative stress and apoptosis that have been involved in cardiac injury. Cisplatin usage is associated with the cardiotoxicity including arrhythmia, myocarditis, cardiomyopathy and congestive heart failure [1,2,3,4,5]. CP-containing chemotherapy to the patients encourages deterioration in the abundance of various antioxidants in the plasma, which may lead to the failure of anti-oxidative defense mechanism. CP induces lacerations in the vascular components of the cardiac tissues of treated animals. The vascular endothelium perform various tasks and CP consequent endothelial deteriorations are accountable for several health complications, such as atherosclerosis, high blood pressure, thrombosis, vasculitis, sepsis and bleeding etc. [9]
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