Protective effects of glutamine on lipopolysaccharide/D-galactosamine-induced fulminant hepatitis in mice

Fulminant hepatitis remains a critical health problem owing to its high mortality rate and the lack of effective therapies. An increasing number of studies have shown that glutamine supplementation provides protective benefits in inflammation-related disorders, but the pharmacological significance o...

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Bibliographic Details
Published in:Experimental biology and medicine (Maywood, N.J.) N.J.), 2023-01, Vol.248 (1), p.70-78
Main Authors: Yang, Mengxin, Zhang, Xinyue, Zhao, Shuang, Shao, Ruyue, Fan, Kerui, Hu, Kai, Zhang, Li, Yang, Yongqiang
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Caspase 3 - pharmacology
Caspases - pharmacology
Galactosamine - pharmacology
Glutamine
Lipopolysaccharides - pharmacology
Liver - pathology
Massive Hepatic Necrosis - pathology
Mice
Original Research
Tumor Necrosis Factor-alpha
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Summary:Fulminant hepatitis remains a critical health problem owing to its high mortality rate and the lack of effective therapies. An increasing number of studies have shown that glutamine supplementation provides protective benefits in inflammation-related disorders, but the pharmacological significance of glutamine in lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced fulminant hepatitis remains unclear. In the present study, the potential effects of glutamine on LPS/D-Gal-induced fulminant hepatitis were investigated. Pretreatment with glutamine decreased plasma activities of alanine and aspartate aminotransferases, and ameliorated hepatic morphological abnormalities in LPS/D-Gal-exposed mice. Glutamine pretreatment also inhibited LPS/D-Gal-induced tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) production. In addition, glutamine pretreatment decreased the level of cleaved cysteinyl aspartate–specific proteinase 3 (caspase-3), suppressed the activities of caspase-3, caspase-8, and caspase-9, and reduced the number of cells positive for TdT-mediated dUTP nick-end labeling in LPS/D-Gal-challenged mice. Interestingly, post-treatment with glutamine also provided protective benefits against LPS/D-Gal-induced acute liver injury, although these effects were less robust than those of glutamine pre-treatment. Thus, glutamine may have potential value as a pharmacological intervention in fulminant hepatitis.
ISSN:1535-3702
1535-3699
DOI:10.1177/15353702221126562