Action of Melatonin on Severe Acute Liver Failure in Rats

Salvi, Jeferson de Oliveira; Schemitt, Elizângela Gonçalves; Colares, Josieli Raskopf; Hartmann, Renata Minuzzo; Marroni, Cláudio Augusto; Marroni, Norma Anair Possa

doi:10.9790/3008-1203036275

Cited by 3 publications

(8 citation statements)

References 54 publications

(56 reference statements)

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“…Gln reduced serum levels of AST, ALT, and ALP, while significantly increased levels of these enzymes were found in animals in the TAA group, suggesting massive hepatic impairment after exposure to the xenobiotic. In other studies, Gln was also able to decrease serum levels of these enzymes, thus corroborating our findings[7,14,46].…”

Section: Discussionsupporting

confidence: 92%

“…We also observed an increase in TBARS levels in the livers of animals in the TAA group, which is indicative of increased lipid peroxidation. Other authors found similar increases in TBARS in studies that used TAA to induce liver damage[6,7,43]. Again, Gln administration was able to reduce these levels in our animals, corroborating the findings of several other studies that have demonstrated its protective effect in different experimental models[21,26,47].…”

Section: Discussionsupporting

confidence: 92%

“…GPx acts in an attempt to reduce molecules with oxidative potential, especially hydrogen peroxide and hydroperoxides, which may explain its increased activity in the group of animals that received TAA. Similar results regarding GPx activity were reported in other studies that used the experimental model of TAA-induced SALF and evaluated the antioxidant action of vitamin E and melatonin[6,7].…”

Section: Discussionsupporting

confidence: 86%

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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: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 86%

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Protective action of glutamine in rats with severe acute liver failure

Schemitt¹,

Hartmann²,

Colares³

et al. 2019

WJH

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“…Our research group has conducted studies on the effects of MLT on liver injury and diseases and found that MLT can regulate various molecular pathways such as inflammation, proliferation, apoptosis, metastasis, and autophagy in different situations. 46,49,50 Here, our results suggest that MLT has a powerful antifibrogenic effect, modulating the parameters of oxidative stress, angiogenesis, and inflammation. The action of MLT on the improvement of liver fibrosis seems to make it a promising candidate for clinical trials in chronic liver diseases associated with increased fibrogenesis.…”

Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Antifibrogenic effect of melatonin in rats with experimental liver cirrhosis induced by carbon tetrachloride

et al. 2018

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Background and AimLiver diseases are a major public health problem, accounting for a significant number of hospital visits and admissions and an increasing mortality rate. Melatonin (MLT) is a powerful antioxidant molecule that has been shown to be beneficial under various conditions. The objective was to evaluate the effect of MLT on experimental liver cirrhosis induced by carbon tetrachloride (CCl4) in rats.MethodsTwenty male Wistar rats (230–250 g) were divided into four groups. I: control group (CO); II: CO + MLT; III: CCl4; and IV: CCl4 + MLT. CCl4 was administered intraperitoneally (i.p.) as follows: 10 doses every 5 days, 10 doses every 4 days, and 7 doses every 3 days. MLT was administered i.p. at a dose of 20 mg/kg from the 10th week to the end of the experiment (16th week).ResultsIn the CCl4 + MLT group, we found that MLT caused a decrease in the level of F2‐isoprostanes and NQO1 expression. We also found that MLT reduced the inflammatory process as shown by decreased expressions of NF‐KB/p65 and inducible nitric oxide synthase (iNOS) and a smaller amount of inflammatory infiltrate. MLT reduced the expression of transforming growth factor beta1 (TGF‐β1), alpha‐smooth muscle actin (α‐SMA), and vascular endothelial growth factor (VEGF). Picrosirius staining showed that MLT decreases fibrosis.ConclusionMLT has a potent antifibrogenic effect, modulating the parameters of oxidative stress, angiogenesis, and inflammation.

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Melatonin prevents oxidative stress, inflammatory activity, and DNA damage in cirrhotic rats

Colares¹,

Hartmann²,

Schemitt³

et al. 2022

WJG

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BACKGROUND Cirrhosis is an important health problem characterized by a significant change in liver parenchyma. In animals, this can be reproduced by an experimental model of bile duct ligation (BDL). Melatonin (MLT) is a physiological hormone synthesized from serotonin that has been studied for its beneficial properties, including its antioxidant potential. AIM To evaluate MLT’s effects on oxidative stress, the inflammatory process, and DNA damage in an experimental model of secondary biliary cirrhosis. METHODS Male Wistar rats were divided into 4 groups: Control (CO), CO + MLT, BDL, and BDL + MLT. MLT was administered (20 mg/kg) daily beginning on day 15 after biliary obstruction. On day 29 the animals were killed. Blood samples, liver tissue, and bone marrow were collected for further analysis. RESULTS BDL caused changes in biochemical and histological parameters and markers of inflammatory process. Thiobarbituric acid (0.46 ± 0.01) reactive substance levels, superoxide dismutase activity (2.30 ± 0.07) and nitric oxide levels (2.48 ± 0.36) were significantly lower ( P < 0.001) n the groups that received MLT. DNA damage was also lower ( P < 0.001) in MLT-treated groups (171.6 ± 32.9) than the BDL-only group (295.5 ± 34.8). Tissue damage and the expression of nuclear factor kappa B, interleukin-1β, Nrf2, NQO1 and Hsp70 were significantly lower in animals treated with MLT ( P < 0.001). CONCLUSION When administered to rats with BDL-induced secondary biliary cirrhosis, MLT effectively restored the evaluated parameters.

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Action of Melatonin on Severe Acute Liver Failure in Rats

Cited by 3 publications

References 54 publications

Protective action of glutamine in rats with severe acute liver failure

Protective action of glutamine in rats with severe acute liver failure

Antifibrogenic effect of melatonin in rats with experimental liver cirrhosis induced by carbon tetrachloride

Melatonin prevents oxidative stress, inflammatory activity, and DNA damage in cirrhotic rats

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