Melatonin Attenuates Inflammation, Oxidative Stress, and DNA Damage in Mice with Nonalcoholic Steatohepatitis Induced by a Methionine- and Choline-Deficient Diet.

Autor: Miguel FM; Laboratory of Genetic Toxicology, Postgraduate Program in Cellular and Molecular Biology Applied To Health, Lutheran University of Brazil, Avenida Farroupilha, 8001, CEP 92425900, Canoas, RS, Brazil.; Experimental Laboratory of Pneumological Sciences and Inflammation, Postgraduate Program in Medical Sciences, Federal Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, 2400, CEP 90035003, Porto Alegre, RS, Brazil., Picada JN; Laboratory of Genetic Toxicology, Postgraduate Program in Cellular and Molecular Biology Applied To Health, Lutheran University of Brazil, Avenida Farroupilha, 8001, CEP 92425900, Canoas, RS, Brazil. jnpicada@gmail.com., da Silva JB; Laboratory of Genetic Toxicology, Postgraduate Program in Cellular and Molecular Biology Applied To Health, Lutheran University of Brazil, Avenida Farroupilha, 8001, CEP 92425900, Canoas, RS, Brazil., Schemitt EG; Experimental Laboratory of Pneumological Sciences and Inflammation, Postgraduate Program in Medical Sciences, Federal Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, 2400, CEP 90035003, Porto Alegre, RS, Brazil., Colares JR; Experimental Laboratory of Pneumological Sciences and Inflammation, Postgraduate Program in Medical Sciences, Federal Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, 2400, CEP 90035003, Porto Alegre, RS, Brazil., Hartmann RM; Experimental Laboratory of Pneumological Sciences and Inflammation, Postgraduate Program in Medical Sciences, Federal Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, 2400, CEP 90035003, Porto Alegre, RS, Brazil., Marroni CA; Department of Gastroenterology and Hepatology, Postgraduate Program - Hepatology, Federal University of Health Sciences, Federal University of Health Sciences of Porto Alegre, Rua Sarmento Leite, 245, CEP 90050170, Porto Alegre, RS, Brazil., Marroni NP; Experimental Laboratory of Pneumological Sciences and Inflammation, Postgraduate Program in Medical Sciences, Federal Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, 2400, CEP 90035003, Porto Alegre, RS, Brazil.; Postgraduate Program in Biological Sciences - Physiology, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500, RS, CEP 90050170, Porto Alegre, Brazil.
Jazyk: angličtina
Zdroj: Inflammation [Inflammation] 2022 Oct; Vol. 45 (5), pp. 1968-1984. Date of Electronic Publication: 2022 Apr 13.
DOI: 10.1007/s10753-022-01667-4
Abstrakt: Nonalcoholic steatohepatitis (NASH) is a disease with a high incidence worldwide, but its diagnosis and treatment are poorly managed. In this study, NASH pathophysiology and DNA damage biomarkers were investigated in mice with NASH treated and untreated with melatonin (MLT). C57BL/6 mice were fed a methionine- and choline-deficient (MCD) diet for 4 weeks to develop NASH. Melatonin was administered at 20 mg/kg during the last 2 weeks. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured, and hepatic tissue was dissected for histological analysis, evaluation of lipoperoxidation, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as nuclear factor-erythroid 2 (Nrf2), tumor necrosis factor alpha (TNF-α), inducible nitric oxide synthase (iNOS), and transforming growth factor beta (TGF-β) expression by immunohistochemistry. DNA damage was evaluated using Comet assay, while a micronucleus test in bone marrow was performed to assess the genomic instability associated with the disease. Melatonin decreased AST and ALT, liver inflammatory processes, balloonization, and fibrosis in mice with NASH, decreasing TNF-α, iNOS, and TGF-β, as well as oxidative stress, shown by reducing lipoperoxidation and intensifying Nrf2 expression. The SOD and GPx activities were increased, while CAT was decreased by treatment with MLT. Although the micronucleus frequency was not increased in mice with NASH, a protective effect on DNA was observed with MLT treatment in blood and liver tissues using Comet assay. As conclusions, MLT slows down the progression of NASH, reducing hepatic oxidative stress and inflammatory processes, inhibiting DNA damage via anti-inflammatory and antioxidant actions.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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