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CC BY 4.0 · Journal of Coloproctology 2025; 45(02): s00451809668
DOI: 10.1055/s-0045-1809668
Original Article

Liver-Intestine Axis: Effects of Physical Exercise and Melatonin on Intestinal Implications in Secondary Biliary Cirrhosis

Gabriela dos Santos Martins
1   Experimental Laboratory of Pneumological Sciences and inflammation, Porto Alegre Clinical Hospital (HCPA), Porto Alegre, RS, Brazil
,
Elizângela Gonçalves Schemitt
1   Experimental Laboratory of Pneumological Sciences and inflammation, Porto Alegre Clinical Hospital (HCPA), Porto Alegre, RS, Brazil
,
Henrique Sarubbi Fillmann
2   Department of Endoscopy and Coloproctology, Faculty of Medicine, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil
,
Marilda da Silva Brasil
1   Experimental Laboratory of Pneumological Sciences and inflammation, Porto Alegre Clinical Hospital (HCPA), Porto Alegre, RS, Brazil
,
Sandielly Rebeca Benitez da Fonseca
1   Experimental Laboratory of Pneumological Sciences and inflammation, Porto Alegre Clinical Hospital (HCPA), Porto Alegre, RS, Brazil
,
Millena de Oliveira Engeroff
1   Experimental Laboratory of Pneumological Sciences and inflammation, Porto Alegre Clinical Hospital (HCPA), Porto Alegre, RS, Brazil
,
Maria Amalia Pavanato
3   Department of Physiology and Pharmacology, Federal University of Santa Maria (UFSM), Santa Maria, RS, Brazil
,
Norma Anair Possa Marroni 
1   Experimental Laboratory of Pneumological Sciences and inflammation, Porto Alegre Clinical Hospital (HCPA), Porto Alegre, RS, Brazil
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Abstract

Introduction

Modulation of the liver-gut axis, including interventions that reduce oxidative stress, is essential in the management of cirrhosis and in the prevention of its complications. Physical exercise and the use of antioxidants such as melatonin (MLT) improve oxidative stress by increasing the production of endogenous antioxidants, resulting in a better ability of the body to neutralize free radicals.

Objective

To investigate the effects of EX and the use of MLT, the possible biological markers and mechanisms involved in the disease process.

Materials and Methods

Twenty-six male Wistar rats were used, divided into 4 groups: Control (CO), Bile duct ligation (BDL), BDL + EX, and BDL + MLT. Physical exercise (swimming) was conducted daily, starting on the 15th day after BDL surgery, as well as MLT, intraperitoneally at a dose of 20 mg/kg, lasting until the 28th day, the end of the experiment. Blood, liver, and intestine were collected. Statistical analysis was performed using One-Way ANOVA followed by the student-Newman-Keuls test (p < 0.05).

Results

The treatments were effective in preserving the tissue architecture of the liver and intestine. Hepatic integrity enzymes showed a significant reduction in the EX and MLT groups. The treatments reduced lipid peroxidation (LPO) levels, restored antioxidant activity and total antioxidant capacity, as well as lowered the levels of nitric oxide metabolites. It was found that the treatments activated the Nrf2 pathway and reduced inflammatory mediators.

Conclusion

The treatments (EX and MLT) were effective against the damage assessed in this experimental model, suggesting that these interventions may be promising for future clinical use.

Keywords

Cirrhosis - intestine - oxidative stress - physical exercise - melatonin

Authors' Contribution

Martins GS, Schemitt EG, Brasil M, Fonseca SRB, Marroni NP participated in the production and development of the experimental model; Martins GS, Schemitti EG, Brasil MS, Fonseca SRB, Engeroff MO participated in the application of analysis techniques; Martins GS, Schemitt EG, Fillmann HS, Pavorato MA, Marroni NP participated in data analysis and manuscript review.




Publication History

Received: 25 February 2025

Accepted: 22 May 2025

Article published online:
30 June 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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Bibliographical Record
Gabriela dos Santos Martins, Elizângela Gonçalves Schemitt, Henrique Sarubbi Fillmann, Marilda da Silva Brasil, Sandielly Rebeca Benitez da Fonseca, Millena de Oliveira Engeroff, Maria Amalia Pavanato, Norma Anair Possa Marroni. Liver-Intestine Axis: Effects of Physical Exercise and Melatonin on Intestinal Implications in Secondary Biliary Cirrhosis. Journal of Coloproctology 2025; 45: s00451809668.
DOI: 10.1055/s-0045-1809668
 

  • Referências

  • 1 Tapper EB, Parikh ND. Diagnosis and Management of Cirrhosis and Its Complications: A Review. JAMA 2023; 329 (18) 1589-1602
    PubMedSearch in Google Scholar
  • 2 Albillos A, de Gottardi A, Rescigno M. The gut-liver axis in liver disease: Pathophysiological basis for therapy. J Hepatol 2020; 72 (03) 558-577
    CrossrefPubMedSearch in Google Scholar
  • 3 Wang R, Tang R, Li B, Ma X, Schnabl B, Tilg H. Gut microbiome, liver immunology, and liver diseases. Cell Mol Immunol 2021; 18 (01) 4-17
    CrossrefPubMedSearch in Google Scholar
  • 4 Kountouras J, Billing BH, Scheuer PJ. Prolonged bile duct obstruction: a new experimental model for cirrhosis in the rat. Br J Exp Pathol 1984; 65 (03) 305-311
    PubMedSearch in Google Scholar
  • 5 Colares JR, Hartmann RM, Schemitt EG. et al. Melatonin prevents oxidative stress, inflammatory activity, and DNA damage in cirrhotic rats. World J Gastroenterol 2022; 28 (03) 348-364
    PubMedSearch in Google Scholar
  • 6 Sahoo DK, Heilmann RM, Paital B. et al. Oxidative stress, hormones, and effects of natural antioxidants on intestinal inflammation in inflammatory bowel disease. Front Endocrinol (Lausanne) 2023; 14: 1217165
    PubMedSearch in Google Scholar
  • 7 Duarte-Rojo A, Ruiz-Margáin A, Montaño-Loza AJ, Macías-Rodríguez RU, Ferrando A, Kim WR. Exercise and physical activity for patients with end-stage liver disease: Improving functional status and sarcopenia while on the transplant waiting list. Liver Transpl 2018; 24 (01) 122-139
    CrossrefPubMedSearch in Google Scholar
  • 8 Martins GS, Rosa CGS, Schemitt EG. et al. Action of melatonin and physical exercise on the liver of cirrhotic rats: Study of oxidative stress and the inflammatory process. Hepatol Forum 2024; 5 (04) 184-192
    PubMedSearch in Google Scholar
  • 9 Tordjman S, Chokron S, Delorme R. et al. Melatonin: Pharmacology, Functions and Therapeutic Benefits. Curr Neuropharmacol 2017; 15 (03) 434-443
    CrossrefPubMedSearch in Google Scholar
  • 10 Ferreira RAP, Ramos PS, Salvador AA. et al. The effect of the use of melatonin in the treatment of intestinal inflammatory diseases: an integrative review. Res. Soc. Dev. 2019; (09) e17891263
    Search in Google Scholar
  • 11 Bertolini GR, do Nascimento CM, Artifon EL, Cunha DM, Meireles A. Swimming training and functional assessment of sciatic nociception in rats. Rev Bras Reumatol 2011; 51 (03) 249-259
    PubMedSearch in Google Scholar
  • 12 Rosa CGS, Colares JR, da Fonseca SRB. et al. Sarcopenia, oxidative stress and inflammatory process in muscle of cirrhotic rats - Action of melatonin and physical exercise. Exp Mol Pathol 2021; 121: 104662
    PubMedSearch in Google Scholar
  • 13 Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-254
    CrossrefPubMedSearch in Google Scholar
  • 14 Buege JÁ, Aust SD. Microsomal lipid peroxidation. Methods Enzymol 1978; 52: 302-310
    CrossrefPubMedSearch in Google Scholar
  • 15 Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972; 247 (10) 3170-3175
    CrossrefPubMedSearch in Google Scholar
  • 16 Boveris A, Chance B. The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem J 1973; 134 (03) 707-716
    PubMedSearch in Google Scholar
  • 17 Flohé L, Günzler WA. Assays of glutathione peroxidase. Methods Enzymol 1984; 105: 114-121
    CrossrefPubMedSearch in Google Scholar
  • 18 Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med 1999; 26 (9-10): 1231-1237
    CrossrefPubMedSearch in Google Scholar
  • 19 Granger DL, Anstey NM, Miller WC, Weinberg JB. Measuring nitric oxide production in human clinical studies. Methods Enzymol 1999; 301: 49-61
    PubMedSearch in Google Scholar
  • 20 Ferrari RS, Tieppo M, Rosa DP, Forgiarini Jr LA, Dias AS, Marroni NP. Lung and liver changes due to the induction of cirrhosis in two experimental models. Arq Gastroenterol 2013; 50 (03) 208-213
    PubMedSearch in Google Scholar
  • 21 Gomes JR, Freitas JR, Grassiolli S. Effects of Physical Exercise on the Intestinal Mucosa of Rats Submitted to a Hypothalamic Obesity Condition. Anat Rec (Hoboken) 2016; 299 (10) 1389-1396
    PubMedSearch in Google Scholar
  • 22 Chopyk DM, Grakoui A. Contribution of the Intestinal Microbiome and Gut Barrier to Hepatic Disorders. Gastroenterology 2020; 159 (03) 849-863
    PubMedSearch in Google Scholar
  • 23 Hajighasem A, Farzanegi P, Mazaheri Z. Effects of combined therapy with resveratrol, continuous and interval exercises on apoptosis, oxidative stress, and inflammatory biomarkers in the liver of old rats with non-alcoholic fatty liver disease. Arch Physiol Biochem 2019; 125 (02) 142-149
    PubMedSearch in Google Scholar
  • 24 Philips CA, Augustine P. Gut Barrier and Microbiota in Cirrhosis. J Clin Exp Hepatol 2022; 12 (02) 625-638
    CrossrefPubMedSearch in Google Scholar
  • 25 Qin L, Yao ZQ, Chang Q. et al. Swimming attenuates inflammation, oxidative stress, and apoptosis in a rat model of dextran sulfate sodium-induced chronic colitis. Oncotarget 2017; 8 (05) 7391-7404
    PubMedSearch in Google Scholar
  • 26 Licks F, Hartman RM, Schemitt EG. et al. Inflammatory bowel and oxidative stress changes in an experimental model of portal hypertension: action of N-acetylcysteine. JCOL 2016; 36 (04) 231-239
    Search in Google Scholar
  • 27 Scheffer DDL, Latini A. Exercise-induced immune system response: Anti-inflammatory status on peripheral and central organs. Biochim Biophys Acta Mol Basis Dis 2020; 1866 (10) 165823
    CrossrefPubMedSearch in Google Scholar
  • 28 You T, Arsenis NC, Disanzo BL, Lamonte MJ. Effects of exercise training on chronic inflammation in obesity : current evidence and potential mechanisms. Sports Med 2013; 43 (04) 243-256
    PubMedSearch in Google Scholar
  • 29 Zhao HD, Zhang F, Shen G. et al. Sulforaphane protects liver injury induced by intestinal ischemia reperfusion through Nrf2-ARE pathway. World J Gastroenterol 2010; 16 (24) 3002-3010
    PubMedSearch in Google Scholar
  • 30 Hartmann RM, Licks F, Schemitt EG. et al. Protective effect of glutamine on the main and adjacent organs damaged by ischemia-reperfusion in rats. Protoplasma 2017; 254 (06) 2155-2168
    PubMedSearch in Google Scholar