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A mouse model of the regression of alcoholic hepatitis: Monitoring the regression of hepatic steatosis, inflammation, oxidative stress, and NAD + metabolism upon alcohol withdrawal.
- Source :
-
The Journal of nutritional biochemistry [J Nutr Biochem] 2022 Jan; Vol. 99, pp. 108852. Date of Electronic Publication: 2021 Sep 12. - Publication Year :
- 2022
-
Abstract
- This study aimed to develop a well-characterized mouse model of alcoholic hepatitis (AH) regression. Male C57BL/6J mice were fed a Lieber-DeCarli (LD) control diet or LD containing 5% ethanol for ten days followed by one binge, which is the chronic-binge model of AH developed by the National Institute on Alcohol Abuse and Alcoholism. To determine AH regression, mice previously exposed to ethanol were put on LD control diet and metabolic and inflammatory features were monitored weekly for three weeks. Serum alcohol, total cholesterol, and alanine transaminase levels were increased in ethanol-fed mice, which declined to those of no ethanol controls within one and three weeks after ethanol withdrawal, respectively. Serum malondialdehyde was increased with ethanol feeding, but it was restored to no ethanol control levels within one week. Ethanol-induced changes in the hepatic expression of genes involved in lipogenesis, fatty acid oxidation, ethanol metabolism, and antioxidant response were restored to those of no ethanol controls after 3 weeks of ethanol withdrawal. Also, ethanol-induced hepatic inflammation was gradually decreased during the 3 weeks of ethanol withdrawal. Hepatic nicotinamide adenine dinucleotide (NAD <superscript>+</superscript> ) levels and the expression of enzymes involved in the NAD <superscript>+</superscript> salvage pathway were decreased by ethanol feeding, which was mitigated after ethanol withdrawal. Ethanol significantly lowered hepatic sirtuin 1 expression, but its levels were restored with ethanol cessation. This study established a mouse model of AH regression, which can be used as a preclinical model to study the potential of dietary bioactives or therapeutic agents on AH regression.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Disease Models, Animal
Disease Progression
Fatty Liver etiology
Fatty Liver genetics
Fatty Liver immunology
Hepatitis, Alcoholic etiology
Hepatitis, Alcoholic genetics
Hepatitis, Alcoholic immunology
Humans
Liver immunology
Liver metabolism
Male
Malondialdehyde metabolism
Mice
Mice, Inbred C57BL
Sirtuin 1 genetics
Sirtuin 1 metabolism
Alcoholism complications
Ethanol adverse effects
Fatty Liver metabolism
Hepatitis, Alcoholic metabolism
NAD metabolism
Oxidative Stress
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4847
- Volume :
- 99
- Database :
- MEDLINE
- Journal :
- The Journal of nutritional biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 34525389
- Full Text :
- https://doi.org/10.1016/j.jnutbio.2021.108852