Kelleni Mina Thabet, Amin Entesar Farghaly, Abdelrahman Aly Mohamed
Department of Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt.
J Toxicol. 2015;2015:424813. doi: 10.1155/2015/424813. Epub 2015 Dec 31.
Doxorubicin (DOX) is a widely used antineoplastic drug whose efficacy is limited by its cardiotoxicity. The aim of this study was to investigate the possible protective role of the antidiabetic drugs metformin (250 mg/kg dissolved in DW p.o. for seven days) and sitagliptin (10 mg/kg dissolved in DW p.o. for seven days) in a model of DOX-induced (single dose 15 mg/kg i.p. at the fifth day) cardiotoxicity in rats. Results of our study revealed that pretreatment with metformin or sitagliptin produced significant (P < 0.05) cardiac protection manifested by a significant decrease in serum levels of LDH and CK-MB enzymes and cardiac MDA and total nitrites and nitrates levels, a significant increase in cardiac SOD activity, and remarkable improvement in the histopathological features as well as a significant reduction in the immunohistochemical expression of COX-2, iNOS, and caspase-3 enzymes as compared to DOX group. These results may suggest using metformin and/or sitagliptin as preferable drugs for diabetic patients suffering from cancer and receiving DOX in their chemotherapy regimen.
阿霉素（DOX）是一种广泛使用的抗肿瘤药物，但其疗效受到心脏毒性的限制。本研究的目的是探讨抗糖尿病药物二甲双胍（250mg/kg溶于蒸馏水，口服给药7天）和西他列汀（10mg/kg溶于蒸馏水，口服给药7天）在大鼠阿霉素诱导（第5天腹腔注射单剂量15mg/kg）心脏毒性模型中的可能保护作用。我们的研究结果显示，与阿霉素组相比，二甲双胍或西他列汀预处理产生了显著（P<0.05）的心脏保护作用，表现为血清乳酸脱氢酶（LDH）和肌酸激酶同工酶（CK-MB）水平、心脏丙二醛（MDA）以及总亚硝酸盐和硝酸盐水平显著降低，心脏超氧化物歧化酶（SOD）活性显著增加，组织病理学特征显著改善，环氧合酶-2（COX-2）、诱导型一氧化氮合酶（iNOS）和半胱天冬酶-3（caspase-3）酶的免疫组化表达显著降低。这些结果可能提示，对于患有癌症且化疗方案中接受阿霉素治疗的糖尿病患者，二甲双胍和/或西他列汀可作为首选药物。
