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Gut Microbiota Modulates the Protective Role of Ginsenoside Compound K Against Sodium Valproate-Induced Hepatotoxicity in Rat

This study aimed to investigate the potential role of gut microbiota in the hepatotoxicity of sodium valproate (SVP) and the protective effect of ginsenoside compound K (G-CK) administration against SVP-induced hepatotoxicity in rats. Measurements of 16S rRNA showed that SVP supplementation led to a...

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Detalles Bibliográficos
Autores principales: Zhou, Luping, Zeng, Xiangchang, Liao, Jianwei, Chen, Lulu, Ouyang, Dongsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302921/
https://www.ncbi.nlm.nih.gov/pubmed/35875589
http://dx.doi.org/10.3389/fmicb.2022.936585
Descripción
Sumario:This study aimed to investigate the potential role of gut microbiota in the hepatotoxicity of sodium valproate (SVP) and the protective effect of ginsenoside compound K (G-CK) administration against SVP-induced hepatotoxicity in rats. Measurements of 16S rRNA showed that SVP supplementation led to a 140.749- and 248.900-fold increase in the relative abundance of Akkermansia muciniphila (A. muciniphila) and Bifidobacterium pseudolongum (B. pseudolongum), respectively (p < 0.05). The increase in A. muciniphila was almost completely reversed by G-CK treatment. The relative abundance of A. muciniphila was strongly positively correlated with aspartate transaminase (AST) and alanine aminotransferase (ALT) levels (r > 0.78, p < 0.05). The PICRUSt analysis showed that G-CK could inhibit the changes of seven pathways caused by SVP, of which four pathways, including the fatty acid biosynthesis, lipid biosynthesis, glycolysis/gluconeogenesis, and pyruvate metabolism, were found to be negatively correlated with AST and ALT levels (r ≥ 0.70, p < 0.01 or < 0.05). In addition, the glycolysis/gluconeogenesis and pyruvate metabolism were negatively correlated with the relative abundance of A. muciniphila (r > 0.65, p < 0.01 or < 0.05). This alteration of the gut microbiota composition that resulted in observed changes to the glycolysis/gluconeogenesis and pyruvate metabolism may be involved in both the hepatotoxicity of SVP and the protective effect of G-CK administration against SVP-induced hepatotoxicity. Our study provides new evidence linking the gut microbiota with SVP-induced hepatotoxicity.