Elieh-Ali-Komi Daniel, Yarmohammadi Fatemeh, Nezamabadi Maryam, Khirehgesh Mohammad Reza, Kiani Mitra, Rashidi Khodabakhsh, Mohammadi-Noori Ehsan, Salehi Nahid, Dehpour Ahmad Reza, Kiani Amir
Institute of Allergology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.
Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology, Berlin, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):4279-4290. doi: 10.1007/s00210-024-03545-2. Epub 2024 Oct 24.
Isoproterenol (ISO) usage is limited by its potential for cardiotoxicity. We sought to investigate the potential of agmatine in mitigating ISO-induced cardiotoxicity. Agmatine (100 mg/kg/day) was intraperitoneally administered to Wistar rats for 7 days in the presence or absence of cardiotoxicity induced by subcutaneous injection of ISO (85 mg/kg) on the sixth and seventh days. ECG parameters, lactate dehydrogenase (LDH), malondialdehyde (MDA), and creatinine phosphokinase (CPK) were investigated. Changes in cardiac tissue were also investigated using H&E staining. The heart weight/body weight ratio increased in ISO-treated rats. In the agmatine + ISO group, the increased heart rate observed in ISO-treated rats was reversed (317.2 ± 10.5 vs 452.2 ± 10.61, P < 0.001). Agmatine ameliorated the change in PR, RR, and ST intervals and the QRS complex, which was reduced by ISO. Treatment with saline, ISO, and agmatine had no significant effect on papillary muscle stimulation (P > 0.05). The administration of agmatine to ISO-receiving group could mitigate several parameters when compared to ISO-receiving group including increasing papillary muscle contraction (0.83 vs 0.71 N/M respectively, P < 0.01), decreasing LDH levels (660 ng/ml vs 1080 ng/ml, respectively, P < 0.05), decreasing CPK levels (377 U/l vs 642 U/l, respectively, P < 0.05) and decreasing MDA levels (20.32 µM/l vs 46.83 µM/l, P < 0.001). Coadministration of agmatine and ISO is capable of ameliorating ISO cardiotoxicity by antioxidant effects and controlling the hemostasis of calcium in myocytes.
异丙肾上腺素(ISO)的使用因其潜在的心脏毒性而受到限制。我们试图研究胍丁胺减轻ISO诱导的心脏毒性的潜力。在第6天和第7天,对Wistar大鼠皮下注射ISO(85mg/kg)诱导或不诱导心脏毒性的情况下,腹腔注射胍丁胺(100mg/kg/天),持续7天。研究了心电图参数、乳酸脱氢酶(LDH)、丙二醛(MDA)和肌酸磷酸激酶(CPK)。还使用苏木精和伊红染色研究了心脏组织的变化。ISO处理的大鼠心脏重量/体重比增加。在胍丁胺+ISO组中,ISO处理的大鼠中观察到的心率增加得到了逆转(317.2±10.5对452.2±10.61,P<0.001)。胍丁胺改善了PR、RR和ST间期以及QRS波群的变化,这些变化被ISO降低。生理盐水、ISO和胍丁胺处理对乳头肌刺激无显著影响(P>0.05)。与接受ISO的组相比,向接受ISO的组施用胍丁胺可以减轻几个参数,包括增加乳头肌收缩(分别为0.83对0.71N/M,P<0.01)、降低LDH水平(分别为660ng/ml对1080ng/ml,P<0.05)、降低CPK水平(分别为377U/l对642U/l,P<0.05)和降低MDA水平(20.32µM/l对46.83µM/l,P<0.001)。胍丁胺和ISO联合给药能够通过抗氧化作用和控制心肌细胞内钙的稳态来减轻ISO的心脏毒性。