Acacia hydaspica R. Parker prevents doxorubicin-induced cardiac injury by attenuation of oxidative stress and structural Cardiomyocyte alterations in rats

Abstract

BackgroundThe use of doxorubicin (DOX) an anthracycline antineoplastic agent is withdrawn due to its cardio-toxic side effects. Oxidative stress has been recognized as the primary cause of DOX induced cardiotoxicity. We have investigated whether polyphenol rich ethyl acetate extract of Acacia hydaspica (AHE) can attenuate doxorubicin-induced cardiotoxicity via inhibition of oxidative stress.MethodsAHE was administered orally to rats once daily for 6 weeks at doses of 200 and 400 mg/kg b.w. DOX (3 mg/kg b.w. i.p., single dose/week) was administered for 6 weeks (chronic model). The parameters studied to evaluate cardioprotective potential were the serum cardiac function biomarkers (CK, CKMB, AST and LDH), hematological parameters, cardiac tissue antioxidant enzymatic status and oxidative stress markers, and histopathological analysis to validate biochemical findings.ResultsChronic 6 week treatment of DOX significantly deteriorated cardiac function biomarkers and decreased the activities of antioxidant enzymes, whereas significant increase in oxidative stress biomarkers was noticed in comparison to control group. AHE dose dependently protected DOX-induced leakage of cardiac enzymes in serum and ameliorated DOX-induced oxidative stress; as evidenced by decreasing lipid peroxidation, H2O2 and NO content with increase in phase I and phase II antioxidant enzymes. Doxorubicin treatment produced severe morphological lesions, leucopenia, decrease in red blood cell counts and hemoglobin concentrations. AHE co-treatment protected the heart and blood elements from the toxic effects of doxorubicin as indicated by the recovery of hematological parameters to normal values and prevention of myocardial injuries in a dose dependent way. The protective potency of AHE (400 mg/kg b.w) was equivalent to silymarin.ConclusionResults revealed that AHE showed protective effects against DOX induce cardiotoxicity. The protective effect might attribute to its polyphenolic constituents and antioxidant properties. AHE might be helpful in combination therapies as safer and efficient.

Cardioprotective Potential of Murraya koenigii (L.) Spreng. Leaf Extract against Doxorubicin-Induced Cardiotoxicity in Rats

“…However, the treatment with aqueous Murraya leaf extract increases SOD and catalase level suggesting its antioxidant and ROS-scavenging nature. Not only the present study but also many previous studies on the protective effect against doxorubicin-induced cardiotoxicity based on the antioxidant property have shown a similar effect on SOD and the catalase activity [47,48,51,52,54]. Total antioxidant status of the doxorubicin-treated animals was greatly reduced in the present study suggesting that doxorubicin treatment causes depletion of antioxidants in the body.…”

“…According to the results of the present study, elevated AST and LDH levels were significantly reduced by the pretreatment with aqueous plant extract compared to the doxorubicin control. Many previous studies have also shown that compounds with antioxidant property may bring down the cardiac biomarkers in rats treated with doxorubicin [47][48][49].…”

“…Serum biomarkers of myocardial toxicity including AST and LDH indicate the loss of cell membrane integrity of myocytes [46]. It is believed that enhanced production of free radicals in doxorubicin metabolism may enhance myocyte degeneration and hence increase the enzyme leakage [47]. Although these two are not very specific biomarkers for the detection of myocardial cell injury, their elevation together with more specific and sensitive biomarkers such as cTnI specify the cardiac damage.…”

“…Antioxidant compounds and antioxidant enzymes including GSH, GPx, GR, SOD, and catalase protect the body against oxidative-stress-mediated tissue injury [47]. GSH is considered as the most important intracellular hydrophilic antioxidant which protects the cells from free radical damage [50].…”

Yiqi Fumai lyophilized injection attenuates doxorubicin-induced cardiotoxicity, hepatotoxicity and nephrotoxicity in rats by inhibition of oxidative stress, inflammation and apoptosis

“…Doxorubicin (DOX) is an anthracycline anticancer drug, which can treat a variety of human neoplasms such as leukemias, lymphomas, breast cancer, sarcomas and other malignancies. 1,2 However, DOX has a main adverse effect, cardiotoxicity, which limits its clinical application. In addition, researchers nd that DOX can also lead to severe hepato-renal toxicities.…”