Afsar Tayyaba, Razak Suhail, Batoo Khalid Mujasam, Khan Muhammad Rashid
Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
BMC Complement Altern Med. 2017 Dec 29;17(1):554. doi: 10.1186/s12906-017-2061-0.
The use of doxorubicin (DOX) an anthracycline antineoplastic agent is withdrawn due to its cardio-toxic side effects.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.
AHE 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.
Chronic 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, HO 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.
Results 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.
由于其心脏毒性副作用，蒽环类抗肿瘤药物阿霉素（DOX）的使用已被停用。氧化应激已被认为是阿霉素诱导心脏毒性的主要原因。我们研究了富含多酚的阿拉伯金合欢乙酸乙酯提取物（AHE）是否能通过抑制氧化应激来减轻阿霉素诱导的心脏毒性。
将AHE以200和400mg/kg体重的剂量每日口服给予大鼠，持续6周。阿霉素（3mg/kg体重，腹腔注射，每周单剂量）给药6周（慢性模型）。用于评估心脏保护潜力的研究参数包括血清心脏功能生物标志物（CK、CKMB、AST和LDH）、血液学参数、心脏组织抗氧化酶状态和氧化应激标志物，以及用于验证生化结果的组织病理学分析。
阿霉素6周的慢性治疗显著恶化了心脏功能生物标志物，并降低了抗氧化酶的活性，而与对照组相比，氧化应激生物标志物显著增加。AHE剂量依赖性地保护了阿霉素诱导的血清中心脏酶的泄漏，并改善了阿霉素诱导的氧化应激；脂质过氧化、HO和NO含量降低，I相和II相抗氧化酶增加证明了这一点。阿霉素治疗产生了严重的形态学损伤、白细胞减少、红细胞计数和血红蛋白浓度降低。AHE联合治疗保护心脏和血液成分免受阿霉素的毒性作用，血液学参数恢复到正常值以及剂量依赖性地预防心肌损伤表明了这一点。AHE（400mg/kg体重）的保护效力与水飞蓟宾相当。
结果表明，AHE对阿霉素诱导的心脏毒性具有保护作用。这种保护作用可能归因于其多酚成分和抗氧化特性。AHE作为更安全有效的药物，可能有助于联合治疗。
