RGD Reference Report - Mice deficient in aldo-keto reductase 1a (Akr1a) are resistant to thioacetamide-induced liver injury. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Mice deficient in aldo-keto reductase 1a (Akr1a) are resistant to thioacetamide-induced liver injury.

Authors: Homma, Takujiro  Shirato, Takaya  Akihara, Ryusuke  Kobayashi, Sho  Lee, Jaeyong  Yamada, Ken-Ichi  Miyata, Satoshi  Takahashi, Motoko  Fujii, Junichi 
Citation: Homma T, etal., Toxicol Lett. 2018 Sep 15;294:37-43. doi: 10.1016/j.toxlet.2018.05.015. Epub 2018 May 12.
RGD ID: 27226688
Pubmed: PMID:29763686   (View Abstract at PubMed)
DOI: DOI:10.1016/j.toxlet.2018.05.015   (Journal Full-text)

Aldehyde reductase (Akr1a) has been reported to be involved in detoxification of reactive aldehydes as well as in the synthesis of bioactive compounds such as ascorbic acid (AsA). Because Akr1a is expressed at high levels in the liver and is involved in xenobiotic metabolism, our objective was to investigate the hepato-protective role of Akr1a in a thioacetamide (TAA)-induced hepatotoxicity model using Akr1a-deficient (Akr1a-/-) mice. Wild-type (WT) and Akr1a-/- mice were injected intraperitoneally with TAA and the extent of liver injury in the acute phase was assessed. Intriguingly, the extent of TAA-induced liver damage was less in the Akr1a-/- mice than in the WT mice. Biomarkers for the ER stress-induced apoptosis pathway were markedly decreased in the livers of Akr1a-/- mice, whereas AsA levels in plasma did not change significantly in any of the mice. In the liver, TAA is converted to reactive metabolites such as TAA S-oxide and then to TAA S, S-dioxide via the action of CYP2E1. In Akr1a-/- mice, CYP2E1 activity was relatively lower than WT mice at the basal level, leading to reactive TAA metabolites being produced at lower levels after the TAA treatment. The levels of liver proteins that were modified with these metabolites were also lower in the Akr1a-/- mice than the WT mice after the TAA treatment. Furthermore, after a lethal dose of a TAA challenge, the WT mice all died within 36 h, whereas almost all of the Akr1a-/- mice survived. These collective results suggest that Akr1a-/- mice are resistant to TAA-induced liver injury, and it follows that the absence of Akr1a might modulate TAA bioactivation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Chemical and Drug Induced Liver Injury  ISOAkr1a1 (Mus musculus)27226688; 27226688 RGD 
Chemical and Drug Induced Liver Injury  IMP 27226688 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Akr1a1  (aldo-keto reductase family 1 member A1)

Genes (Mus musculus)
Akr1a1  (aldo-keto reductase family 1, member A1)

Genes (Homo sapiens)
AKR1A1  (aldo-keto reductase family 1 member A1)


Additional Information