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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2022; 28(3): 348-364
Published online Jan 21, 2022. doi: 10.3748/wjg.v28.i3.348
Melatonin prevents oxidative stress, inflammatory activity, and DNA damage in cirrhotic rats
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
Josieli R Colares, Renata M Hartmann, Elizângela G Schemitt, Sandielly R B Fonseca, Norma P Marroni, Medical Sciences Program, Universidade Federal do Rio Grande do Sul, Porto Alegre 90050-170, Brazil
Marilda S Brasil, Norma P Marroni, Biological Sciences Program, Universidade Federal do Rio Grande do Sul, Porto Alegre 90050-170, Brazil
Jaqueline N Picada, Cellular and Molecular Biology Program, Lutheran University of Brazil (ULBRA), Canoas 92425-900, Brazil
Alexandre S Dias, Aline F Bueno, Pneumological Sciences Program, Universidade Federal do Rio Grande do Sul, Porto Alegre 90050-170, Brazil
Cláudio A Marroni, Posgraduate Program in Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre 90050-170, Brazil
Author contributions: Colares JR, Marroni CA and Marroni NP participated in study design and development, data analysis and interpretation, and writing the manuscript; Schemitt EG, Hartmann RM, Fonseca SRB, Brasil MS, Bueno AF and Dias AS, participated in the oxidative stress and immunohistochemistry analyses and interpretation of results.
Supported by Fundo de Incentivo à Pesquisa e Eventos (FIPE).
Institutional review board statement: This study was conducted at the Laboratory of Experimental Hepatology and Gastroenterology, Hospital de Clínicas of Porto Alegre after approval from the Institutional Animal Care and Use Committee (opinion no. CEUA-HCPA No. 2016-0373).
Institutional animal care and use committee statement: This study was conducted at the Animal Experimentation Unit, Hospital de Clínicas of Porto Alegre after approval from the Institutional Animal Care and Use Committee (opinion no. CEUA-HCPA No. 2016-0373).
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This open-access article was selected by an in-house editor and was fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution-NonCommercial-ShareAlike license (CC BY-NC 4.0), which permits others to distribute, remix, adapt, and build upon this work for non-commercial purposes, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Norma P Marroni, PhD, Doctor, Full Professor, Research Scientist, Medical Sciences Program, Universidade Federal do Rio Grande do Sul, Rua Jose Kanan Aranha, Porto Alegre 90050-170, Brazil. nmarroni@terra.com.br
Received: May 5, 2021
Peer-review started: May 5, 2021
First decision: June 12, 2021
Revised: June 24, 2021
Accepted: January 11, 2022
Article in press: January 11, 2022
Published online: January 21, 2022
ARTICLE HIGHLIGHTS
Research background
Liver cirrhosis, which causes millions of deaths per year, is characterized by the appearance of fibrotic nodules and septa caused by chronic harmful stimuli. Oxidative damage may play a key role in the development and progression of cirrhosis. Thus, promoting the identification of new antioxidant compounds can contribute to enriching the available therapeutic arsenal.
Research motivation
Numerous studies using different experimental models have reported melatonin (MLT)’s protective effects on the liver. The antioxidant effect of MLT is related to its high solubility in lipids, which facilitates its passage through cell membranes. Thus, understanding the mechanisms involved in the protective action of MLT in cirrhosis can lead to the development of new therapeutic strategies that can lead to improved medical care.
Research objectives
The aim of the study was to evaluate the protective action of MLT in cirrhosis induced by bile duct ligation (BDL) in rats.
Research methods
Wistar rats were divided into a control group, a MLT control group, a BDL group, and a BDL group treated with MLT. Intraperitoneal administration of MLT at a dose of 20 mg/kg of body weight started on the 15th day after the beginning of the experiment and continued daily for 14 d. At the end of the experiment, the animals were euthanized. Blood was collected for liver integrity tests and the liver was collected for histological analysis, DNA damage assessment, and biochemical and Western blot analysis of proteins related to oxidative stress and the inflammatory process.
Research results
MLT promoted a significant improvement in the biochemical parameters of oxidative stress markers and the inflammatory process. DNA damage was also lower in animals treated with MLT after undergoing BDL. Tissue damage and protein expression assessed by immunohistochemistry and Western blot analysis were significantly lower in animals treated with MLT.
Research conclusions
According to the results obtained in the evaluated parameters, treatment with MLT reduced tissue and cell damage in the liver. Our results suggest that MLT may be of use of in patients with cirrhosis.
Research perspectives
Further studies are needed to assess the long-term efficacy and safety of MLT administration in cirrhotic patients before it can be recommended in clinical practice.
