Beneficio potencial de la rifaximina en la prevención del carcinoma hepatocelular mediante la modulación de la microbiota en un modelo experimental de enfermedad por hígado graso no alcohólico

Autores/as

  • Jéssica Tonin Ferrari Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre. Rio Grande do Sul, Brazil. https://orcid.org/0000-0003-4022-5362
  • Gabriel Tayguara Silveira Guerreiro Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre. Rio Grande do Sul, Brazil. https://orcid.org/0000-0002-0550-4561
  • Larisse Longo Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre. Rio Grande do Sul, Brazil. https://orcid.org/0000-0002-4453-7227
  • Themis Reverbel da Silveira Experimental Laboratory of Hepatology and Gastroenterology, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre. Rio Grande do Sul, Brazil.
  • Carlos Thadeu Schmidt Cerski Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre. Rio Grande do Sul, Brazil.
  • Erica Tozawa Unit of Surgical Pathology, Hospital de Clínicas de Porto Alegre, Porto Alegre. Rio Grande do Sul, Brazil. https://orcid.org/0000-0002-3021-4435
  • Cláudia P Oliveira Department of Gastroenterology (LIM07), Faculdade de Medicina da Universidade de São Paulo. São Paulo, Brazil. https://orcid.org/0000-0002-2848-417X
  • Mário Reis Álvares-da-Silva Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre. Rio Grande do Sul, Brazil. https://orcid.org/0000-0002-5001-246X
  • Carolina Uribe-Cruz Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre. Rio Grande do Sul, Brazil. https://orcid.org/0000-0002-0526-3067

DOI:

https://doi.org/10.52787/agl.v53i3.329

Palabras clave:

Microbiota intestinal, carcinoma hepatocelular, enfermedad del hígado graso no alcohólico, rifaximina

Resumen

Objetivo. Evaluar los efectos de la rifaximina mediante la modulación de la microbiota en un modelo de carcinoma hepatocelular secundario a enfermedad por hígado graso no alcohólico.

Métodos. Se dividieron tres grupos de 8 ratas Sprague-Dawley macho adultas cada uno de la siguiente manera: el grupo carcinoma hepatocelular: ratas alimentadas con una dieta alta en grasas y deficiente en colina más dietilnitrosamina como carcinógeno; el grupo tratado con carcinoma hepatocelular: ratas alimentadas con una dieta alta en grasas y deficiente en colina más dietilnitrosamina y tratadas con rifaximina y el grupo control: animales alimentados con una dieta estándar y agua. Las ratas fueron sometidas a eutanasia a las 16 semanas. Se realizaron análisis de la patología hepática para determinar la gravedad de la enfermedad por hígado graso no alcohólico y la clasificación del cáncer, la expresión génica en tejidos intestinales y hepáticos y la microbiota fecal.

Resultados. Todos los animales del grupo de carcinoma hepatocelular tenían enfermedad por hígado graso no alcohólico y desarrollaron lesiones de carcinoma hepatocelular. Los animales del grupo con rifaximina mostraron una enfermedad por hígado graso no alcohólico menos intensa (evaluada por el puntaje de actividad de la enfermedad por hígado graso no alcohólico NAS]) en comparación con el grupo carcinoma hepatocelular. Los grupos carcinoma hepatocelular y carcinoma hepatocelular + rifaximina mostraron áreas de fibrosis evaluadas con rojo picrosirio. Tres animales del grupo con rifaximina no desarrollaron lesiones cancerosas. Los análisis de la microbiota intestinal mostraron diferencias en la diversidad y composición de los grupos control vs carcinoma hepatocelular y rifaximina. Se identificaron 12 géneros diferencialmente abundantes entre los grupos carcinoma hepatocelular y rifaximina. En el grupo con rifaximina disminuyó la expresión génica de las uniones estrechas intestinales.

Conclusiones. En un modelo de roedores de carcinoma hepatocelular relacionado con enfermedad por hígado graso no alcohólico, la rifaximina disminuye la gravedad histológica de la enfermedad por hígado graso no alcohólico y la aparición de carcinoma hepatocelular, probablemente mediante la modulación de la microbiota intestinal independientemente de los marcadores de permeabilidad intestinal.

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Publicado

30-09-2023

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Tonin Ferrari, J., Tayguara Silveira Guerreiro, G., Longo, L., Reverbel da Silveira, T., Thadeu Schmidt Cerski, C., Tozawa, E., P Oliveira, C., Reis Álvares-da-Silva, M., & Uribe-Cruz, C. (2023). Beneficio potencial de la rifaximina en la prevención del carcinoma hepatocelular mediante la modulación de la microbiota en un modelo experimental de enfermedad por hígado graso no alcohólico. Acta Gastroenterológica Latinoamericana, 53(3), 265–282. https://doi.org/10.52787/agl.v53i3.329

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Vol. 53 Núm. 3 (2023): Acta Gastroenterológica Latinoamericana

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Derechos de autor 2023 Jéssica Tonin Ferrari, Gabriel Tayguara Silveira Guerreiro, Larisse Longo, Themis Reverbel da Silveira, Carlos Thadeu Schmidt Cerski, Erica Tozawa, Cláudia P Oliveira, Mário Reis Álvares-da-Silva, Carolina Uribe-Cruz

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Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial-CompartirIgual 4.0.