Protective action of glutamine in rats with severe acute liver failure
Protective action of glutamine in rats with severe acute liver failure作者机构：Laboratory of Experimental Hepatology and Gastroenterology Hospital de Clínicas de Porto Alegre Laboratory of Oxidative Stress and Antioxidants Universidade Luterana do Brasil
出 版 物：《World Journal of Hepatology》 (世界肝病学杂志（英文版）（电子版）)
年 卷 期：2019年第11卷第3期
页 面：273-286页
基 金：FIPE/Hospital de Clinicas of Porto Alegre
主 题：Thioacetamide Cytokines Oxidative stress Inflammation Liver failure Chemical and drug induced liver injury Glutamine
摘 要：BACKGROUND Severe acute liver failure(SALF) is a rare, but high-mortality, rapidly evolving syndrome that leads to hepatocyte degeneration with impaired liver ***(TAA) is a known xenobiotic, which promotes the increase of the formation of reactive oxygen species. Erythroid 2-related factor 2(Nrf2) activates the antioxidant protection of cells. Studies have evidenced the involvement of inflammatory mediators in conditions of oxidative *** To evaluate the antioxidant effects of glutamine on Nrf2 activation and NFκBmediated inflammation in rats with TAA-induced *** Male Wistar rats(n = 28) were divided into four groups: control,control+glutamine, TAA, and TAA + glutamine. Two TAA doses(400 mg/kg)were administered intraperitoneally, 8 h apart. Glutamine(25 mg/kg) was administered at 30 min, 24 h, and 36 h. At 48 h, blood was collected for liver integrity analysis [aspartate aminotransferase(AST), alanine aminotransferase(ALT), and alkaline phosphatase(ALP)]. The liver was harvested for histology and assessment of oxidative stress [thiobarbituric acid-reactive substances(TBARS), catalase(CAT), glutathione peroxidase(GPx), glutathione S-transferase(GST), glutathione(GSH), Nrf2, Kelch-like ECH-associated protein 1(Keap1),NADPH quinone oxidoreductase1(NQO1), superoxide dismutase(SOD)] and inflammatory *** TAA caused disruption of the hepatic parenchyma, with inflammatoryinfiltration, massive necrosis, and ballooning degeneration. Glutamine mitigated this tissue damage, with visible regeneration of hepatic parenchyma; decreased TBARS(P 0.001), GSH(P 0.01), IL-1β, IL6, and TNFα levels(P 0.01) in hepatic tissue; and decreased blood levels of AST, ALT, and ALP(P 0.05). In addition, CAT, GPx, and GST activities were restored in the glutamine group(P0.01, P 0.01, and P 0.001, respectively vs TAA alone). Glutamine increased expression of Nrf2(P 0.05), NQO1, and SOD(P 0.01), as well as levels of IL-10(P 0.001), while decr
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