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.

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http://dx.doi.org/10.1007/s00210-024-03545-2DOI Listing

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