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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
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.
Core Tip: The experimental model of secondary biliary cirrhosis, by ligation of the main bile duct, mimics the clinical situation, with biochemical, enzymatic, histological changes, and similar biological, inflammatory, genotoxic markers and oxidative stress triggers. Melatonin, used as an antioxidant therapeutic agent, has been shown to be effective in reversing the changes caused at different levels due to its antioxidant, anti-inflammatory, cytoprotective action, including a reduction in DNA damage, with significant improvement and future therapeutic potential.
