Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Neuroscience Research Center; Department of Physiology, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran.
Saudi J Kidney Dis Transpl. 2020 Sep-Oct;31(5):1025-1033. doi: 10.4103/1319-2442.301167.
Kidneys have been shown to be the main target for toxins. Lipopolysaccharide (LPS) is a bacterial endotoxin which can involve in pathogenesis of endotoxemia-caused kidney dysfunction. Excessive production of free radicals such as nitric oxide (NO) and pro-inflammatory cytokines have been reported to contribute in kidney dysfunction. The purpose of this study was to investigate the effect of inducible nitric oxide synthase (iNOS) inhibition against LPS-induced kidney dysfunction in rats. Male rats were assigned into five groups. Control animals were injected saline; LPS group received 1 mg/kg of LPS for five weeks; LPS-AG50, LPS-AG100, and LPS-AG150 groups received AG (50, 100, and 150 mg/kg, respectively) 30 min before LPS. All drugs were administered intraperitoneally. LPS injection enhanced the level of blood urea nitrogen (BUN) and creatinine compared with the control group. Pretreatment with AG resulted in a significant reduction in BUN and creatinine in LPS-AG100 and LPS-AG 150 groups with respect to the LPS group. LPS administration led to a significant increase in interleukin (IL)-6, malondialdehyde (MDA), and NO metabolites as well as a significant decrease in the content of total thiol groups and superoxide dismutase (SOD) and catalase (CAT) activity. Pretreatment with AG reduced the level of IL-6, MDA, and NO metabolites and enhanced the content of total thiol groups and SOD and CAT activity in LPS-AG groups compared to the LPS group. The results of the present study show that inhibition of iNOS has a protective effect against kidney dysfunction caused by LPS.
肾脏已被证明是毒素的主要靶器官。脂多糖 (LPS) 是一种细菌内毒素,可参与内毒素血症引起的肾功能障碍的发病机制。据报道,过多的自由基如一氧化氮 (NO) 和促炎细胞因子的产生有助于肾功能障碍。本研究的目的是研究诱导型一氧化氮合酶 (iNOS) 抑制对 LPS 诱导的大鼠肾功能障碍的影响。雄性大鼠被分为五组。对照组动物注射生理盐水;LPS 组给予 1 mg/kg LPS 连续 5 周;LPS-AG50、LPS-AG100 和 LPS-AG150 组分别在 LPS 前 30 分钟给予 AG(分别为 50、100 和 150 mg/kg)。所有药物均腹腔注射。LPS 注射使血尿素氮 (BUN) 和肌酐水平较对照组升高。与 LPS 组相比,AG 预处理可使 LPS-AG100 和 LPS-AG150 组的 BUN 和肌酐显著降低。LPS 给药导致白细胞介素 (IL)-6、丙二醛 (MDA) 和 NO 代谢物显著增加,总巯基含量以及超氧化物歧化酶 (SOD) 和过氧化氢酶 (CAT) 活性显著降低。与 LPS 组相比,AG 预处理可降低 LPS-AG 组的 IL-6、MDA 和 NO 代谢物水平,提高总巯基含量以及 SOD 和 CAT 活性。本研究结果表明,iNOS 抑制对 LPS 引起的肾功能障碍具有保护作用。