研究动态
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利福平对多柔比星诱导的小鼠心脏毒性的功效研究。

Rifampicin efficacy against doxorubicin-induced cardiotoxicity in mice.

发表日期:2023 Aug 21
作者: Omnia A Basal, Rasha F Zahran, Entsar A Saad
来源: ANTIOXIDANTS & REDOX SIGNALING

摘要:

多柔比星对心脏的毒性效应限制了它在癌症治疗中的临床用途。本研究旨在首次调查利福霉素对多柔比星诱导的小鼠心脏毒性的疗效。将40只成年雄性白化小鼠分为四组:对照组、多柔比星组、多柔比星+利福霉素 0.107 组和多柔比星+利福霉素 0.214 组,每组 n=10。进行心脏组织病理学和心脏功能检测的生化测定[肌酸激酶(CK)、乳酸脱氢酶(LDH)、天冬氨酸氨基转移酶(AST)、心肌肌钙蛋白 I(cTnI)、心房利钠肽(ANP)和血管内皮生长因子(VEGF)],氧化应激(丙二醛(MDA)和超氧化物歧化酶(SOD))和矿物质(磷、钠、钾和钙)等。通过组织学方法证实了使用总剂量为15 mg/kg 的多柔比星诱导的心脏毒性。心肌细胞显示充血、坏死、水肿和炎性细胞浸润。生化学上观察到 LDH、CK 和 AST 活性升高(p<0.001),cTnI 和 ANP 水平增高(p<0.001),氧化应激增加(MDA,p<0.001),矿物质水平升高(Na、K,p<0.001,P,p<0.01,Ca,p<0.05),VEGF 浓度降低(p<0.001),抗氧化物降低(SOD,p<0.001)的多柔比星组与对照组相比。与利福霉素联合治疗明显降低了氧化应激增加、高 Na 和 K、 LDH、CK、AST、cTnI 和 ANP 的水平,并将低 SOD 水平提高到正常范围(p<0.001)。我们的组织学数据支持了我们的生化数据;0.214 mg/kg剂量的利福霉素的改善效果优于 0.107 剂量。我们的结果表明,利福霉素通过其抗氧化作用可以帮助保护机体免受多柔比星诱导的心脏毒性的影响。© 2023. Egyptian Society of Cardiology.
The toxic effect of doxorubicin on the heart limits its clinical usage in cancer therapy. This work intended to investigate, for the first time, the efficacy of rifampicin administration against doxorubicin-induction of cardiotoxicity in mice. Forty adult male albino mice were distributed into four sets: Control, Doxorubicin, Doxorubicin + Rifampicin 0.107, and Doxorubicin + Rifampicin 0.214, with n = 10 for each. Heart histopathology and biochemical assays for heart function tests [creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), cardiac troponin I (cTnI), atrial natriuretic peptide (ANP), and vascular endothelial growth factor (VEGF)], oxidative stress [malondialdehyde (MDA) and superoxide dismutase (SOD)], and minerals [phosphorus, sodium, potassium, and calcium] were done.Doxorubicin-induced cardiotoxicity using a total dose of 15 mg/kg was confirmed histologically. Cardiomyocytes showed congestion, necrosis, edema, and inflammatory cell infiltration. Biochemically, elevations in LDH, CK, and AST activities, p < 0.001, as well as increases in cTnI and ANP levels, p < 0.001, increased oxidative stress (MDA, p < 0.001), high minerals (Na, K, p < 0.001, P, p < 0.01, and Ca, p < 0.05), with reduced VEGF concentration, p < 0.001, and low antioxidant (SOD, p < 0.001) were observed in the Doxorubicin group compared to control. Co-treatment with rifampicin significantly (p < 0.001) reduced the increased oxidative stress, high Na and K, increased LDH, CK, AST, cTnI, and ANP, and elevated the low SOD toward the normal ranges. Our histological data supported our biochemical data; rifampicin dose 0.214 mg/kg showed better improvements than dose 0107.Our results demonstrated that rifampicin could help protect the body against doxorubicin-induced cardiotoxicity through its antioxidative effect.© 2023. Egyptian Society of Cardiology.