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

Abstract

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.

• Authors: Mengxin Yang, Xinyue Zhang, Shuang Zhao, Ruyue Shao, Kerui Fan, Kai Hu, Li Zhang, Yongqiang Yang
• Journal: Experimental biology and medicine (Maywood, N.J.) (Exp Biol Med (Maywood)) Vol. 248 Issue 1 Pg. 70-78 (01 2023) ISSN: 1535-3699 [Electronic] England
• PMID: 36259626 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipopolysaccharides
• Caspase 3
• Glutamine
• Caspases
• Galactosamine
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Mice
• Lipopolysaccharides (pharmacology)
• Massive Hepatic Necrosis (pathology)
• Caspase 3 (pharmacology)
• Glutamine
• Caspases (pharmacology)
• Apoptosis
• Galactosamine (pharmacology)
• Liver (pathology)
• Tumor Necrosis Factor-alpha