Nimbal S K, Nagashettikoppa K, Jeedi N M, Patil S B, Mali N
Department of Pharmacology, KLE College of Pharmacy, Hubballi - 580031 (A Constituent Unit of KLE Academy of Higher Education and Research, Belagavi), India.
Arch Razi Inst. 2024 Aug 1;79(4):727-740. doi: 10.32592/ARI.2024.79.4.727. eCollection 2024 Aug.
The doxorubicin, an anthracycline derivative, is a cytotoxic agent with proven efficacy in various malignancies. The clinical utility has been limited due to its dose -dependent cardiac toxicity. To evaluate the role of L. on doxorubicin-induced cardiotoxicity in rats and to predict the role of L. by and in vivo methods. Invitro studies were conducted on L. Cardiotoxicity was produced by administration of doxorubicin (Dox-15 mg/kg ip. for two weeks). Ethanolic extract and fractions of L. (250 and 500 mg/kg, p.o.) were administered as pretreatment for 15 days followed by Doxorubicin 2.5 mg/kg i.p. on alternate day for two weeks. The parameters like body weight, food and water consumption, cardiac specific markers like Creatine Kinase (CK-MB), Lactate Dehydrogenase (LDH) and Cardiac Troponin-I (cTnl), ECG changes, antioxidant parameters like superoxide dismutase (SOD), glutathione (GSH), catalase (CAT) and lipid peroxidation (MDA) were monitored. Histopathological studies of the heart were also performed to evaluate myocardial toxicity. Dox treatment results in cardiomyopathy characterised by elevated cardiac biomarkers and deficiency of antioxidant enzymes. By reducing the elevated levels of biomarker enzymes like LDH and CK-MB and the absence of cTnI, pretreatment with the EECB (500mg/kg) significantly protected the myocardium from the toxic effects of Dox. In addition, the EECB increased the reduced levels of GSH, SOD, and CAT while decreasing the elevated levels of malondialdehyde (MDA) in cardiac tissue.
阿霉素是一种蒽环类衍生物,是一种细胞毒性药物,已证实在各种恶性肿瘤中具有疗效。由于其剂量依赖性心脏毒性,其临床应用受到限制。为了评估L.对阿霉素诱导的大鼠心脏毒性的作用,并通过体内外方法预测L.的作用。对L.进行了体外研究。通过给予阿霉素(15mg/kg腹腔注射,持续两周)产生心脏毒性。L.的乙醇提取物和馏分(250和500mg/kg,口服)作为预处理给药15天,随后每隔一天腹腔注射2.5mg/kg阿霉素,持续两周。监测体重、食物和水消耗等参数、心脏特异性标志物如肌酸激酶(CK-MB)、乳酸脱氢酶(LDH)和心肌肌钙蛋白I(cTnl)、心电图变化、抗氧化参数如超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、过氧化氢酶(CAT)和脂质过氧化(MDA)。还进行了心脏的组织病理学研究以评估心肌毒性。阿霉素治疗导致以心脏生物标志物升高和抗氧化酶缺乏为特征的心肌病。通过降低LDH和CK-MB等生物标志物酶的升高水平以及不存在cTnI,用EECB(500mg/kg)预处理可显著保护心肌免受阿霉素的毒性作用。此外,EECB增加了心脏组织中降低的GSH、SOD和CAT水平,同时降低了丙二醛(MDA)的升高水平。