Department of Pharmacology, I. T. S College of Pharmacy, Ghaziabad, UP, India.
Department of Pharmacology, Kharvel Subharti College of Pharmacy, Swami Vivekanand Subharti University, Meerut, UP, India.
Vasc Health Risk Manag. 2022 Dec 13;18:857-866. doi: 10.2147/VHRM.S381485. eCollection 2022.
Several mechanisms have been explored for the anthracycline myocardial toxicity. These are free-radical generation, myocyte apoptosis, lipid peroxidation, mitochondrial deterioration, and direct repression of muscle-specific gene expression. Adriamycin (Doxorubicin) is a potent anti-cancer agent. Adriamycin in prolonged use is fatal and generates free radicals that lead to dose-dependent cardiac toxicity.
The intent of the study was to explore the protective activity of candesartan and quercetin in cardiomyopathy induced by doxorubicin in rats.
To induce cardiac toxicity, rats were intraperitoneally treated with doxorubicin (06 equivalent injections of 2.5 mg/kg, i. p. at 48 hour interval for 02 consecutive weeks to achieve a cumulative dose of 15 mg/kg). Individual and combined oral treatment of candesartan (5 mg/kg/day) and quercetin (10 mg/kg/day) was administered for four weeks.
Following cardiomyopathy, heart/body weight ratio (3.526 × 10), serum creatine kinase (352.4±16.99 IU/L), lactate dehydrogenase (661.7±20.45 IU/L) levels were elevated in addition to altered lipid profile (TC - 118.4±4.25 mg/dL, TG - 263.3±9.99 mg/dL, VLDL - 52.66±1.99 mg/dL, LDL - 52.99±5.80 mg/dL and HDL - 12.78±0.36 mg/dL). The pre-cotreatment of candesartan and quercetin significantly restored the values to normal. The increased level of lipid peroxides (33.12±1.63 µmol/mg protein), serum troponin-T (1.82 ± 0.11 pg/mL) and nitric oxide (13.33±0.73 nmol/mg protein) level along with attenuating antioxidant profile, ie catalase, glutathione and superoxide dismutase (1.43±0.12 nmol/mg protein, 8.48±0.42 nmol/mg protein and 2.09±0.031 U/mg protein) were reversed to normal. Morphometry and histopathologic changes represented a beneficial effect of single and combination pre-cotreatment of drugs which significantly decreases adriamycin cardiac toxicity.
The overall result depicts more beneficial and cardioprotective effect of quercetin and candesartan combination as compared to their individual effects in doxorubicin treated animals. Therefore, this combination might be a suitable option to treat the cardiotoxic effect of doxorubicin.
已经探索了几种蒽环类药物心肌毒性的机制。这些机制包括自由基生成、心肌细胞凋亡、脂质过氧化、线粒体恶化以及肌肉特异性基因表达的直接抑制。阿霉素（多柔比星）是一种有效的抗癌药物。长期使用阿霉素会产生致命的自由基，导致剂量依赖性的心脏毒性。
本研究旨在探讨坎地沙坦和槲皮素在阿霉素诱导的大鼠心肌病中的保护作用。
为了诱导心脏毒性，大鼠腹腔内注射阿霉素（06 等效剂量 2.5mg/kg，每 48 小时注射一次，连续 2 周，达到 15mg/kg 的累积剂量）。坎地沙坦（5mg/kg/天）和槲皮素（10mg/kg/天）单独和联合口服治疗 4 周。
在心肌病发生后，心脏/体重比（3.526×10）、血清肌酸激酶（352.4±16.99IU/L）、乳酸脱氢酶（661.7±20.45IU/L）水平升高，此外脂质谱也发生改变（TC-118.4±4.25mg/dL、TG-263.3±9.99mg/dL、VLDL-52.66±1.99mg/dL、LDL-52.99±5.80mg/dL 和 HDL-12.78±0.36mg/dL）。坎地沙坦和槲皮素的预先治疗显著将这些值恢复正常。脂质过氧化物（33.12±1.63µmol/mg 蛋白）、血清肌钙蛋白-T（1.82±0.11pg/mL）和一氧化氮（13.33±0.73nmol/mg 蛋白）水平升高以及抗氧化剂谱（即过氧化氢酶、谷胱甘肽和超氧化物歧化酶）减弱（1.43±0.12nmol/mg 蛋白、8.48±0.42nmol/mg 蛋白和 2.09±0.031U/mg 蛋白）也恢复正常。形态计量学和组织病理学变化代表了药物单一和联合预先治疗的有益作用，显著降低了阿霉素的心脏毒性。
与单独使用相比，槲皮素和坎地沙坦联合使用具有更有益和心脏保护作用，因此，这种联合可能是治疗阿霉素心脏毒性的一种合适选择。
