Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran.
Cardiovasc Toxicol. 2020 Oct;20(5):474-481. doi: 10.1007/s12012-020-09570-w.
Myocardial dysfunction, a major component of sepsis-induced multiorgan failure, contributes to the production of massive amounts of pro-inflammatory cytokines. Nitric oxide (NO) is known to act as a precursor of free radicals in inflammation. This research was conducted to assess the effect of aminoguanidine (AG) on lipopolysaccharide (LPS)-induced heart injury. 50 male rats were categorized into five groups (n = 10): (1) control, (2) LPS, (3) LPS-AG50, (4) LPS-AG100, and (5) LPS-AG150. LPS (1 mg/kg) was injected for 5 weeks, and AG (50, 100 and 150 mg/kg) was injected 30 min prior to LPS administration. All drugs were injected intraperitoneally. LPS-evolved cardiovascular toxicity was indicated by the augmentation in the level of nitric oxide (NO) metabolites, interleukin (IL)-6 and malondialdehyde (MDA), as well as reduced contents of total thiol groups, catalase (CAT), and superoxide dismutase (SOD) activity in serum, heart, and aortic tissues. In AG treated groups, noxious effects of LPS were not observed in the serum and harvested tissues. AG reduced MDA, NO metabolites, and IL- 6 and increased total thiol, CAT, and SOD activity in the heart, aorta and serum. As an inhibitor of inducible NO synthase (iNOS), AG further reduced LPS-induced oxidative stress and inflammation, hence considered as cardioprotective.
心肌功能障碍是脓毒症多器官衰竭的主要组成部分,导致大量促炎细胞因子的产生。一氧化氮(NO)已知在炎症中作为自由基的前体发挥作用。这项研究旨在评估氨基胍(AG)对脂多糖(LPS)诱导的心脏损伤的影响。将 50 只雄性大鼠分为五组(n = 10):(1)对照组,(2)LPS 组,(3)LPS-AG50 组,(4)LPS-AG100 组和(5)LPS-AG150 组。用 LPS(1mg/kg)注射 5 周,AG(50、100 和 150mg/kg)在 LPS 给药前 30 分钟注射。所有药物均腹腔内注射。LPS 诱导的心血管毒性表现为血清中一氧化氮(NO)代谢物、白细胞介素(IL)-6 和丙二醛(MDA)水平的升高,以及血清、心脏和主动脉组织中总巯基含量、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)活性的降低。在 AG 治疗组中,未观察到 LPS 在血清和收获组织中的有害作用。AG 降低了 MDA、NO 代谢物和 IL-6,并增加了心脏、主动脉和血清中的总巯基、CAT 和 SOD 活性。作为诱导型一氧化氮合酶(iNOS)的抑制剂,AG 进一步降低了 LPS 诱导的氧化应激和炎症,因此被认为具有心脏保护作用。