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

World Journal of gastroenterology 2022年第3期28卷 348-364页

作者： Josieli R Colares Renata M Hartmann elizângela g schemitt Sandielly R B Fonseca Marilda S Brasil Jaqueline N Picada Alexandre S Dias Aline F Bueno Cláudio A Marroni Norma P Marroni Medical Sciences Program Universidade Federal do Rio Grande do SulPorto Alegre 90050-170Brazil Marilda S BrasilNorma Biological Sciences Program Universidade Federal do Rio Grande do SulPorto Alegre 90050-170Brazil Cellular and Molecular Biology Program Lutheran University of Brazil(ULBRA)Canoas 92425-900Brazil Pneumological Sciences Program Universidade Federal do Rio Grande do SulPorto Alegre 90050-170Brazil Posgraduate Program in Hepatology Universidade Federal de Ciências da Saúde de Porto AlegrePorto Alegre 90050-170Brazil

BACKgROUND Cirrhosis is an important health problem characterized by a significant change in liver *** 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 *** To evaluate MLT’s effects on oxidative stress,the inflammatory process,and DNA damage in an experimental model of secondary biliary *** Male Wistar rats were divided into 4 groups:Control(CO),CO+MLT,BDL,and BDL+*** was administered(20 mg/kg)daily beginning on day 15 after biliary *** day 29 the animals were *** samples,liver tissue,and bone marrow were collected for further *** BDL caused changes in biochemical and histological parameters and markers of inflammatory *** 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(Pgroups that received *** damage was also lower(Pgroups(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.

关键词： Antioxidants Secondary biliary cirrhosis Oxidative stress Melatonin Bile duct ligation

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Melatonin restores zinc levels,activates the Keap1/Nrf2 pathway,and modulates endoplasmic reticular stress and HSP in rats with chronic hepatotoxicity

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World Journal of gastrointestinal Pharmacology and Therapeutics 2022年第2期13卷 11-22页

作者： Silvia Bona Sabrina Alves Fernandes Andrea C Janz Moreira graziella Rodrigues elizângela g schemitt Fabio Cangeri Di Naso Cláudio A Marroni Norma P Marroni Medical Sciences Program Universidade Federal do Rio Grande do SulPorto Alegre 90035-903Rio Grande do SulBrazil Posgraduate Program in Hepatology Universidade Federal de Ciências da Saúde de Porto AlegrePorto Alegre 90040-001Rio Grande do SulBrazil Biological Sciences Program Universidade Federal do Rio Grande do SulPorto Alegre 90050-170Rio Grande do SulBrazil Postgraduate Program in Pneumological Sciences Universidade Federal do Rio Grande do SulPorto Alegre 90000-000Rio Grande do SulBrazil

BACKgROUND Melatonin(MLT)is a potent antioxidant molecule that is shown to have a beneficial effect in various pathological situations,due to its action against free *** To evaluate the effect of MLT on carbon tetrachloride(CCl_(4))induced liver injury in rats in terms of oxidative stress,reticular stress,and cell *** Twenty male Wistar rats(230-250 g)were divided into four groups:Control rats,rats treated with MLT alone,rats treated with CCl_(4)alone,and rats treated with CCl_(4)plus ***_(4)was administered as follows:Ten doses every 5 d,ten every 4 d,and seven every 3 *** was administered intraperitoneally at a dose of 20 mg/kg from the 10th wk to the end of the experiment(16th wk).RESULTS MLT was able to reduce the release of liver enzymes in the bloodstream and to decrease oxidative stress in CCl_(4)treated rats by decreasing the level of thiobarbituric acid reactive substances and increasing superoxide dismutase activity,with a lower reduction in serum zinc levels,guaranteeing a reduction in liver damage;additionally,it increased the expression of nuclear factor(erythroid-derived 2)-like 2 and decreased the expression of Kelch-like ECH-associated protein *** also decreased the expression of the proteins associated with endoplasmic reticulum stress,i.e.,glucose-regulated protein 78 and activating transcription factor 6,as well as of heat shock factor 1 and heat shock protein *** MLT has a hepatoprotective effect in an experimental model of CCl_(4)-induced liver injury,since it reduces oxidative stress,restores zinc levels,and modulates endoplasmic reticulum stress.

关键词： Liver injury Cell damage Antioxidant Melatonin Carbon tetrachloride

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Antioxidant and anti-inflammatory action of melatonin in an experimental model of secondary biliary cirrhosis induced by bile duct ligation

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World Journal of gastroenterology 2016年第40期22卷 8918-8928页

作者： Josieli Raskopf Colares elizângela goncalves schemitt Renata Minuzzo Hartmann Francielli Licks Mariana do Couto Soares Adriane Dal Bosco Norma Possa Marroni graduate Program in Medical Sciences Universidade Federal do Rio Grande do Sul Porto Alegre 90040-060 Brazil Laboratory of Experimental Hepatology and gastroenterology Hospital de Clínicas de Porto Alegre Porto Alegre 90035-903 Brazil Laboratory of Oxidative Stress and Antioxidants Universidade Luterana do Brasil Canoas 92425-900 Brazil graduate Program in Physiology Universidade Federal do Rio Grande do Sul Porto Alegre 90050-170 Brazil

AIM To evaluate the effects of melatonin(Mel) on oxidative stress in an experimental model of bile duct ligation(BDL).METHODS Male Wistar rats(n = 32, weight ± 300 g) were allocated across four groups: CO(sham BDL), BDL(BDL surgery), CO + Mel(sham BDL and Mel administration) and BDL + Mel(BDL surgery and Mel administration). Mel was administered intraperitoneally for 2 wk, starting on postoperative day 15, at a dose of 20 mg/*** Mel was effective at the different standards, reestablishing normal liver enzyme levels, reducing the hepatosomatic and splenosomatic indices, restoring lipoperoxidation and antioxidant enzyme concentrations, reducing fibrosis and inflammation, and thereby reducing liver tissue injury in the treated *** The results of this study suggest a protective effect of Mel when administered to rats with secondary biliary cirrhosis induced by BDL.

关键词：抗氧化剂肝硬化纤维变性 Melatonin 氧化应力

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Protective action of glutamine in rats with severe acute liver failure

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World Journal of Hepatology 2019年第3期11卷 273-286页

作者： elizangela g schemitt Renata M Hartmann Josieli R Colares Francielli Licks Jéferson O Salvi Cláudio A Marroni Norma P Marroni Laboratory of Experimental Hepatology and gastroenterology Hospital de Clínicas de Porto Alegre Laboratory of Oxidative Stress and Antioxidants Universidade Luterana do Brasil

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 gSH(P gPx, and gST activities were restored in the glutamine group(Pglutamine 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

关键词： Thioacetamide Cytokines Oxidative stress Inflammation Liver failure Chemical and drug induced liver injury glutamine

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N-acetylcysteine modulates angiogenesis and vasodilation in stomach such as DNA damage in blood of portal hypertensive rats

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World Journal of gastroenterology 2015年第43期21卷 12351-12360页

作者： Francielli Licks Renata Minuzzo Hartmann Camila Marques elizangela schemitt Josieli Raskopf Colares Mariana do Couto Soares Juliana Reys Camila Fisher Juliana da Silva Norma Possa Marroni Universidade Federal do Rio grande do Sul Instituto de Tecnologia do Paraná Universidade Luterana do Brasil

AIM: To evaluate the antioxidant effect of N-acetylcysteine(NAC) on the stomach of rats with portal ***: Twenty-four male Wistar rats weighing ± 250 g were divided into four experimental groups(n =6 each): Sham-operated(SO),SO + NAC,partial portal vein ligation(PPVL),and PPVL + NAC. Treatment with NAC in a dose of 10 mg/kg(i.p.) diluted in 0.6 m L of saline solution was administered daily for 7 d starting 8 d after the surgery. Animals from the PPVL and SO group received saline solution(0.6 m L) for the same period of time as the PPVL + NAC and SO + NAC group. On the 15 th day the animals were anesthetized and we evaluated portal pressure by cannulating mesenteric artery. After,we removed the stomach for further analysis. We performed immunohistochemical analysis for endothelial nitric oxide synthase(e NOS),vascular endothelial growth factor(VEgF),and nitrotirosine(NTT) proteins in stomach. We also evaluated e NOS and VEgF by Western blot analysis and assessed DNA damage in blood samples by the comet ***: The portal hypertension group exhibited increases in portal pressure when compared to SO group(29.8 ± 1.8 vs 12.0 ± 0.3 mm Hg)(P gF(34.9 ± 4.7 vs 17.46 ± 2.6 pixels)(P group. The expression of e NOS(0.39 ± 0.03 vs 0.25 ± 0.03 a.μ)(P gF(0.38 ± 0.04 vs 0.26 ± 0.04 a.μ)(P ge by comet assay,and observed an increase on damage index and damage frequency on those animals. NAC decreased portal pressure values in PPVL + NAC animals(16.46 ± 2 vs 29.8 ± 1.8 mm Hg)(P < 0.001) when compared to PPVL. The expression of e NOS(14.60 ± 4.1 vs 56.8 ± 3.7 pixels)(P < 0.001

关键词： N-Acetylcysteine Portal hypertension gastropathy Oxidative stress Antioxidant

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