Glutamine prevents oxidative stress in a model of portal hypertension

Zabot, Gilmara Pandolfo; Carvalhal, Gustavo F.; Marroni, Norma Possa; Licks, Francielli; Hartmann, Renata Minuzzo; Silva, Vinícius Duval da; Fillmann, Henrique Sarubbi

doi:10.3748/wjg.v23.i25.4529

Cited by 13 publications

(8 citation statements)

References 42 publications

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“…Several studies in humans have shown that Gln modulates the expression of genes related to the activation of pathways involved in several disease states[22-25]. Furthermore, studies conducted in different experimental models have demonstrated beneficial effects of Gln on the rat liver, bowel, and stomach[21,26-30].…”

Section: Introductionmentioning

confidence: 99%

Protective action of glutamine in rats with severe acute liver failure

Schemitt¹,

Hartmann²,

Colares³

et al. 2019

WJH

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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.

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Section: Introductionmentioning

confidence: 99%

Protective action of glutamine in rats with severe acute liver failure

Schemitt¹,

Hartmann²,

Colares³

et al. 2019

WJH

Self Cite

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“…The very early age at PVT presentation of our MTHFR TT carriers is unusual and several factors may contribute to this prematurity: leaking of bacterial lipopolysaccharide from the intestine into the portal vein may cause in ammasome activation [15,16] and thrombin generation [17,18], the latter further supported by the oxidation of lipids, abundant in the portal circulation [19,20]; on this background, the additional oxidative effect of elevated HC may anticipate acute thrombosis in MTHFR TT carriers [8].…”

Section: Discussionmentioning

confidence: 99%

Homozygous Mthfr C677t Carriers Develop Idiopathic Portal Vein Thrombosis Twenty Years Earlier Than Wild Type

D’Andrea

Arcaro

Marottoli

et al. 2022

Preprint

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Objective: To compare age at occlusion and plasma homocysteine (HC) in patients with idiopathic portal vein thrombosis (PVT) genotyped for methylene tetrahydrofolate reductase (MTHFR) rs1801133 (C®T667 transition), to identify which clinical or laboratory variables influenced age at first PVT, including the prothrombin rs1799963 PT (G®A transition at position 20210) (PT) mutation. Methods: Retrospective cross-sectional cohort survey on 17 MTHFR TT, 45 MTHFR TC and 24 MTHFR CC participants with idiopathic PVT who contributed age, sex, age at PVT, smoking status, plasma HC and natural anticoagulant concentrations. Results: Age at PVT was lower in MTHFR TT than MTHFR TC and CC (31±8 vs. 46±16 vs. 52±14 years, respectively, p=0.001); median (IQR) plasma HC was higher in MTHFR TT than in the other groups [17 (12.6,25.0) vs. 10 (7.4,13.1) vs. 11.9 (8.1,5.8) μmol/l, respectively, p=0.002)]. MTHFR TT and protein C independently predicted age at PVT (p<0.0001 and p=0.04 respectively); MTHFR TT independently predicted plasma HC (p=0.05). Smoking and sex predicted cavernoma (p=0.002 and p=0.02 respectively). Compound MTHFR TT with PT GA had no lowering effect on age at first VTE compared to MTHFR TT alone (37±7 vs. 30±8 years). Conclusions: MTHFR TT anticipates age at PVT by an average of 20 years compared to other MTHFR genotypes. PT GA had no age lowering effect combined with MTHFR TT. Smoking predicts cavernoma formation, suggesting that smoking may associate with recurrent subclinical PVT before the symptomatic presentation.

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“…The partial portal vein ligation model is the most commonly used to study prehepatic PH. Several experimental studies have shown that partial portal vein ligation produces abnormalities equivalent to PH in humans 17 .…”

Section: Discussionmentioning

confidence: 99%

Carvedilol as Primary Prophylaxis for Gastric Variceal Bleeding in Portal Hypertension Model in Rats

Bertoldi

Guetter

Coltro

et al. 2020

ABCD, arq. bras. cir. dig.

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Background: Portal hypertension (PH) can be measured indirectly through a hepatic vein pressure gradient greater than 5 mmHg. Cirrhosis is the leading cause for PH and can present as complications ascites, hepatic dysfunction, renal dysfunction, and esophagogastric varices, characterizing gastropathy. Aim: To evaluate the use of carvedilol as primary prophylaxis in the development of collateral circulation in rats submitted to the partial portal vein ligament (PPVL) model. Method: This is a combined qualitative and quantitative experimental study in which 32 Wistar rats were divided into four groups (8 animals in each): group I - cirrhosis + carvedilol (PPVL + C); group II - cirrhosis + vehicle (PPVL); group III - control + carvedilol (SO-sham-operated + C); group IV - control + vehicle (SO-sham-operated). After seven days of the surgical procedure (PPVL or sham), carvedilol (10 mg/kg) or vehicle (1 mL normal saline) were administered to the respective groups daily for seven days. Results: The histological analysis showed no hepatic alteration in any group and a decrease in edema and vasodilatation in the PPVL + C group. The laboratory evaluation of liver function did not show a statistically significant change between the groups. Conclusion: Carvedilol was shown to have a positive effect on gastric varices without significant adverse effects.

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Glutamine prevents oxidative stress in a model of portal hypertension

Cited by 13 publications

References 42 publications

Protective action of glutamine in rats with severe acute liver failure

Protective action of glutamine in rats with severe acute liver failure

Homozygous Mthfr C677t Carriers Develop Idiopathic Portal Vein Thrombosis Twenty Years Earlier Than Wild Type

Carvedilol as Primary Prophylaxis for Gastric Variceal Bleeding in Portal Hypertension Model in Rats

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