The protective and therapeutic effects of agmatine on isoproterenol-induced myocardial injury in rats

Zeynep Ulutas, Semih Tapsiz, Onural Ozhan, Mehmet Sarihan, Azibe Yildiz, Merve Durhan, Nigar Vardi, Yilmaz Cigremis, Leyla Buyukkorkmaz, Hakan Parlakpinar
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Abstract

Chronic inflammation and oxidative stress can contribute to the development of cardiovascular diseases. Isoproterenol (ISO), a synthetic catecholamine, is used to study the effects of drugs on cardiotoxicity. Agmatine (AGM) is a type of biogenic amine produced through the decarboxylation of arginine. The purpose of the current study was to evaluate the effects of AGM against ISO-induced cardiotoxicity due to the described roles of AGM in cardiovascular disease. Four groups of thirty-two Wistar Albino rats were divided equally as control, ISO, AGM+ISO, and ISO+AGM. ISO was administered intraperitoneally (i.p.) twice at a dose of 150 mg/kg, at 24-hour intervals. Prior to and after ISO injection, 20 mg/kg of AGM was injected i.p. Hemodynamic measurements and serum and tissue biochemical analyses were evaluated at the end of the experiment. The levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) in the tissue were measured. In the ISO group, levels of lactate dehydrogenase (LDH) and creatine kinase (CK) were increased significantly (p<0.05). Co-administration of ISO and AGM significantly reduced CK and LDH levels (p<0.05). MDA levels increased in the ISO-treated group but decreased in the AGM-treated groups (p<0.05). Notably, there was a reduction in the CAT level in the ISO treatment group (p<0.05). CAT was found to be significantly increased (p<0.05) in the groups that received AGM compared to the ISO group. AGM+ISO group had a reduced density of degenerated cardiomyocytes and granulation tissue compared to the ISO group (p<0.05). Although granulation tissue demonstrated a significant reduction in the ISO+AGM group in comparison to the ISO group (p<0.05). In this study, the results indicate that AGM treatment can potentially inhibit ISO-induced myocardial injury and vascular dysfunction by preserving vascular integrity. Notably, the protective effects of AGM on cardiac damage appear to outweigh its therapeutic benefits, as shown by histopathological analysis
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胍丁氨酸对异丙肾上腺素所致大鼠心肌损伤的保护和治疗作用
慢性炎症和氧化应激可促进心血管疾病的发展。异丙肾上腺素(ISO)是一种合成儿茶酚胺,用于研究药物对心脏毒性的影响。精氨酸(Agmatine, AGM)是一种由精氨酸脱羧而产生的生物胺。由于AGM在心血管疾病中的作用,本研究的目的是评估AGM对iso诱导的心脏毒性的影响。将32只Wistar Albino大鼠平均分为对照组、ISO组、AGM+ISO组和ISO+AGM组。ISO以150 mg/kg的剂量,每隔24小时腹腔(i.p.)给药两次。在注射ISO前后,腹腔注射20 mg/kg AGM,实验结束时进行血液动力学测量和血清及组织生化分析。测定组织中谷胱甘肽(GSH)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、丙二醛(MDA)水平。ISO组乳酸脱氢酶(LDH)和肌酸激酶(CK)水平显著升高(p < 0.05)。ISO和AGM联合施用显著降低了CK和LDH水平(p<0.05)。MDA水平在iso处理组升高,而agm处理组降低(p < 0.05)。值得注意的是,ISO治疗组的CAT水平降低(p<0.05)。与ISO组相比,接受AGM组的CAT显著增加(p<0.05)。与ISO组相比,AGM+ISO组变性心肌细胞和肉芽组织密度降低(p < 0.05)。尽管与ISO组相比,ISO+AGM组肉芽组织明显减少(p < 0.05)。本研究结果表明,AGM治疗可以通过保持血管完整性来潜在地抑制iso诱导的心肌损伤和血管功能障碍。值得注意的是,组织病理学分析显示,AGM对心脏损伤的保护作用似乎超过了它的治疗益处
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