School of Medicine, Shahed University, Tehran, Iran.
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Eur J Pharmacol. 2018 Aug 15;833:307-313. doi: 10.1016/j.ejphar.2018.06.019. Epub 2018 Jun 18.
Acute kidney injury (AKI) is a common complication following severe sepsis, its incidence is increasing, and it is associated with a high rate of morbidity and mortality. Rutin is a glycoside of the bioflavonoid quercetin with various protective effects due to its antioxidant and anti-inflammatory potential. In this research, we tried to assess the protective effect of rutin administration in a model of AKI in C57BL/6 mice. For induction of AKI, lipopolysaccharide (LPS) was injected once (10 mg/kg, i.p.) and rutin was p.o. given at doses of 50 or 200 mg/kg. Treatment of LPS-challenged group with rutin lowered serum level of creatinine and blood urea nitrogen (BUN), restored to some extent renal oxidative stress-related indices such as malondialdehyde (MDA), glutathione (GSH), and activity of superoxide dismutase (SOD) and catalase. In addition, rutin brought back renal nuclear factor-kappaB (NF-κB), toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX2), sirtuin 1 (SIRT1), tumor necrosis factor α (TNFα), interleukin-6, and caspase 3 activity to their control levels. Moreover, protective effect of rutin was in accordance to a dose-dependent manner. Collectively, rutin is capable to mitigate LPS-induced AKI via appropriate modulation of renal oxidative stress, inflammation, and apoptosis.
急性肾损伤(AKI)是严重脓毒症的常见并发症,其发病率正在增加,并且与高发病率和死亡率相关。芦丁是生物类黄酮槲皮素的糖苷,由于其抗氧化和抗炎潜力,具有多种保护作用。在这项研究中,我们试图评估芦丁给药在 C57BL/6 小鼠 AKI 模型中的保护作用。为了诱导 AKI,一次注射脂多糖(LPS)(10mg/kg,ip),并以 50 或 200mg/kg 的剂量口服给予芦丁。芦丁治疗 LPS 挑战组可降低血清肌酐和血尿素氮(BUN)水平,在某种程度上恢复与肾氧化应激相关的指标,如丙二醛(MDA)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和过氧化氢酶的活性。此外,芦丁使核因子-κB(NF-κB)、Toll 样受体 4(TLR4)、环加氧酶-2(COX2)、Sirtuin 1(SIRT1)、肿瘤坏死因子α(TNFα)、白细胞介素-6 和半胱天冬酶 3 的活性恢复到对照水平。此外,芦丁的保护作用与剂量依赖性一致。总之,芦丁能够通过适当调节肾氧化应激、炎症和细胞凋亡来减轻 LPS 诱导的 AKI。