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CC BY 4.0 · Arq Neuropsiquiatr 2023; 81(07): 656-669
DOI: 10.1055/s-0043-1767819
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Anti-inflammatory strategies for hepatic encephalopathy: preclinical studies

Estratégias anti-inflamatórias para encefalopatia hepática: estudos pré-clínicos
Rafaela Pinto Coelho Santos 
1   Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Departamento de Patologia Geral, Laboratório de Patologia Celular e Molecular, Belo Horizonte MG, Brazil.
,
Eliana Cristina de Brito Toscano 
2   Universidade Federal de Juiz de Fora, Faculdade de Medicina, Departamento de Patologia, Laboratório Integrado de Pesquisa em Patologia, Juiz de Fora MG, Brazil.
3   Universidade Federal de Juiz e Fora, Faculdade de Medicina, Programa de Pós-Graduação em Saúde, Juiz de Fora MG, Brazil.
,
Milene Alvarenga Rachid 
1   Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Departamento de Patologia Geral, Laboratório de Patologia Celular e Molecular, Belo Horizonte MG, Brazil.
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Abstract

Hepatic encephalopathy (HE) is a potentially reversible neuropsychiatric syndrome. Often, HE causes cognitive and motor dysfunctions due to an acute or chronic insufficiency of the liver or a shunting between the hepatic portal vein and systemic vasculature. Liver damage induces peripheral changes, such as in the metabolism and peripheral inflammatory responses that trigger exacerbated neuroinflammation. In experimental models, anti-inflammatory strategies have demonstrated neuroprotective effects, leading to a reduction in HE-related cognitive and motor impairments. In this scenario, a growing body of evidence has shown that peripheral and central nervous system inflammation are promising preclinical targets. In this review, we performed an overview of FDA-approved drugs and natural compounds which are used in the treatment of other neurological and nonneurological diseases that have played a neuroprotective role in experimental HE, at least in part, through anti-inflammatory mechanisms. Despite the exciting results from animal models, the available data should be critically interpreted, highlighting the importance of translating the findings for clinical essays.

Resumo

A encefalopatia hepática (EH) é uma síndrome neuropsiquiátrica potencialmente reversível. Muitas vezes a EH causa disfunções cognitivas e motoras devido à insuficiência do fígado ou por um desvio entre a veia porta hepática e a vasculatura sistêmica. O dano no fígado provoca alterações periféricas, como no metabolismo e nas respostas inflamatórias periféricas, que desencadeiam uma neuroinflamação exacerbada. Em modelos experimentais, estratégias anti-inflamatórias têm demonstrado efeitos neuroprotetores, levando a uma redução dos prejuízos cognitivos e motores relacionados à EH. Neste cenário, evidências crescentes têm mostrado a inflamação periférica e no sistema nervoso central como um promissor alvo pré-clínico. Nesta revisão, abordamos uma visão geral de drogas e compostos naturais aprovados pelo FDA para o uso no tratamento de outras doenças neurológicas e não neurológicas, que tiveram papel neuroprotetor na EH experimental, pelo menos em parte, através de mecanismos anti-inflamatórios. Apesar dos resultados empolgantes em modelos animais, os dados avaliados devem ser criticamente interpretados, destacando a importância da tradução dos achados para ensaios clínicos.

Keywords

Hepatic Encephalopathy - Neuroinflammatory Diseases - Neuroprotection - Models, Animal

Palavras-chave

Encefalopatia Hepática - Doenças Neuroinflamatórias - Neuroproteção - Modelos Animais

Authors' Contributions

RPCS, ECBT, MAR: idea; RPCS: literature research; RPCS, ECBT: draft; ECBT, MAR: critical review, both authors contributed equally.


Support

We are grateful to the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (311290/2021–3) and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for their financial support.




Publication History

Received: 08 August 2022

Accepted: 03 December 2022

Article published online:
24 July 2023

© 2023. 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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