Protective action of glutamine in rats with severe acute liver failure

Abstract

BACKGROUND Severe acute liver failure (SALF) is a rare, but high-mortality, rapidly evolving syndrome that leads to hepatocyte degeneration with impaired liver function. Thioacetamide (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 stress. AIM To evaluate the antioxidant effects of glutamine on Nrf2 activation and NFκB-mediated inflammation in rats with TAA-induced IHAG. METHODS 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 process. RESULTS TAA caused disruption of the hepatic parenchyma, with inflammatory infiltration, 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 ( P < 0.01, 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 decreasing expression of Keap1, TLR4, NFκB ( P < 0.001), COX-2 and iNOS, ( P < 0.01), and reducing NO 2 and NO 3 levels ( P < 0.05). CONCLUSION In the TAA experimental model of IHAG, glutamine activated the Nrf2 pathway, thus promoting antioxidant protection, and blunted the NFκB-mediated pathway, reducing inflammation.

Combination of Trans-Resveratrol and ε-Viniferin Induces a Hepatoprotective Effect in Rats with Severe Acute Liver Failure via Reduction of Oxidative Stress and MMP-9 Expression

“…In this study, COX-2 mRNA expression increased in the rat livers of the group injected with TAA and decreased in the group that received TAA followed by ε-viniferin and resveratrol administration. These results (Figure 5) were in line with other studies in which TAA induced hepatotoxicity, The use of allopurinol increased COX-2 mRNA expression, followed by decreased expression after treatment [35], similar to glutamine [7] and proanthocyanidin [36]. As a hepatotoxicant, TAA may stimulate the production of iNOS, and consequently NO synthesis, which leads to an increase inflammation in the liver.…”

“…It manifests unexpectedly with a rapid onset and is frequently fatal, affecting previously healthy individuals [6]. SALF is characterized by a set of inflammatory processes that can lead to parenchymal damage, which may evolve to fibrosis, and in some cases liver cancer, in patients without known liver disorders [7]. One of the main causes of SALF is hepatotoxicity caused by chemical agents, which damage hepatocytes and cause an increase in reactive oxygen species (ROS).…”

Effect of a Synbiotic Containing Lactobacillus paracasei and Opuntia humifusa on a Murine Model of Irritable Bowel Syndrome

“…The plates were analyzed on a calibrated Luminex ® 100/200 reader using MasterPlex QT2010 (MiraiBio, Hitachi, CA, USA). The concentrations were determined from the plate readings and expressed as pg/mL ( Supplementary Table S1 ) [ 35 ].…”

Decreased Expression and Uncoupling of Endothelial Nitric Oxide Synthase in the Cerebral Cortex of Rats with Thioacetamide-Induced Acute Liver Failure

“…TAA-induced ALF is a commonly used animal model of HE [16][17][18][19]. Twenty-four hours after the third injection of TAA (96th h of the experiment), the rats showed visible symptoms of ALF with HE: reduced motor function with stupor or precoma state, and decreased food intake, resulting in 15-20% body weight loss in comparison to control animals (Table 1).…”