Branched-chain amino acids and l-carnitine attenuate lipotoxic hepatocellular damage in rat cirrhotic liver.
Biomed Pharmacother
; 135: 111181, 2021 Mar.
Article
em En
| MEDLINE
| ID: mdl-33395607
ABSTRACT
Branched-chain amino acids (BCAA) reverse malnutrition and l-carnitine leads to the reduction of hyperammonemia and muscle cramps in cirrhotic patients. BCAA and l-carnitine are involved in glucose and fatty acid metabolism, however their mechanistic activity in cirrhotic liver is not fully understood. We aim to define the molecular mechanism(s) and combined effects of BCAA and l-carnitine using a cirrhotic rat model. Rats were administered carbon tetrachloride for 10 weeks to induce cirrhosis. During the last 6 weeks of administration, cirrhotic rats received BCAA, l-carnitine or a combination of BCAA and l-carnitine daily via gavage. We found that BCAA and l-carnitine treatments significantly improved hepatocellular function associated with reduced triglyceride level, lipid deposition and adipophilin expression, in cirrhotic liver. Lipidomic analysis revealed dynamic changes in hepatic lipid composition by BCAA and l-carnitine administrations. BCAA and l-carnitine globally increased molecular species of phosphatidylcholine. Liver triacylglycerol and phosphatidylcholine hydroperoxides were significantly decreased by BCAA and l-carnitine. Furthermore, serum and liver ATP levels were significantly increased in all treatments, which were attributed to the elevation of mature cardiolipins and mitochondrial component gene expressions. Finally, BCAA and l-carnitine dramatically reduced hepatocellular death. In conclusion, BCAA and l-carnitine treatments attenuate hepatocellular damage through the reduction of lipid peroxides and the overall maintenance of mitochondrial integrity within the cirrhotic liver. These effectiveness of BCAA and l-carnitine support the therapeutic strategies in human chronic liver diseases.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
4_TD
/
6_ODS3_enfermedades_notrasmisibles
Problema de saúde:
4_hepatitis
/
6_cirrhosis
/
6_digestive_diseases
/
6_endocrine_disorders
Assunto principal:
Carnitina
/
Peroxidação de Lipídeos
/
Hepatócitos
/
Fígado Gorduroso
/
Doença Hepática Induzida por Substâncias e Drogas
/
Aminoácidos de Cadeia Ramificada
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Fígado
/
Cirrose Hepática Experimental
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Biomed Pharmacother
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Japão