Atli Ozlem, Ilgin Sinem, Altuntas Hakan, Burukoglu Dilek
Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University Eskisehir, Turkey.
Department of Histology, Faculty of Medicine, Osmangazi University Eskisehir, Turkey.
Int J Clin Exp Med. 2015 Mar 15;8(3):3681-90. eCollection 2015.
Although there are possible cardiovascular adverse effects associated with the azithromycin treatment according to some case reports and cohort studies, there is no experimental study evaluating cardiotoxicity in repeated pharmacological doses of this drug. In our study, 15 mg/kg and 30 mg/kg azithromycin were orally administered to rats for 14 days to evaluate the cardiotoxicity of this drug. ECGs of the azithromycin-treated and control animals were recorded. Blood samples were assayed to determine LDH and CK-MB levels. Additionally, CAT, SOD, GSH and MDA levels of heart tissues were measured. According to our ECG recordings, decreased heart rate, prolonged PR and QT intervals, QRS complex and T wave abnormalities were observed in 30 mg/kg azithromycin-administered group significantly when compared with control group. Plasma CK-MB and LDH levels were increased in 30 mg/kg azithromycin-administered group significantly when compared to the control group. In heart tissues, CAT, SOD and GSH levels were decreased while MDA levels were increased in both azithromycin-administered groups significantly when compared with the control group. In conclusion, our findings supported the possible cardiotoxicity risk with azithromycin treatment and also, oxidative stress, which was induced by azithromycin in our study, was thought to be occurred secondary to cardiac toxicity of the drug.
根据一些病例报告和队列研究,虽然阿奇霉素治疗可能存在心血管不良反应,但尚无实验研究评估该药物重复药理剂量下的心脏毒性。在我们的研究中,对大鼠口服给予15mg/kg和30mg/kg的阿奇霉素,持续14天,以评估该药物的心脏毒性。记录阿奇霉素治疗组和对照组动物的心电图。检测血样以测定乳酸脱氢酶(LDH)和肌酸激酶同工酶(CK-MB)水平。此外,还测量了心脏组织中过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)和丙二醛(MDA)的水平。根据我们的心电图记录,与对照组相比,30mg/kg阿奇霉素给药组的心率降低、PR间期和QT间期延长、QRS波群和T波异常显著。与对照组相比,30mg/kg阿奇霉素给药组的血浆CK-MB和LDH水平显著升高。在心脏组织中,与对照组相比,两个阿奇霉素给药组的CAT、SOD和GSH水平均降低,而MDA水平均显著升高。总之,我们的研究结果支持阿奇霉素治疗可能存在心脏毒性风险,而且,我们研究中阿奇霉素诱导的氧化应激被认为是继发于该药物的心脏毒性。