Metabolic Dysfunction-Associated Steatohepatitis (MASH), CDAHFD-Induced, Mouse

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BIOLOGICAL INFORMATION
BACKGROUND INFORMATION
Metabolic dysfunction-associated steatohepatitis (MASH) is a type of metabolic dysfunction-associated steatotic liver disease (MASLD). Feeding mice with a choline-deficient, amino acid-defined high-fat diet (CDAHFD) is a widely used MASH model that induces aminotransferase elevation and hepatic histological changes. This model is applied to evaluate the anti-inflammatory and anti-fibrotic efficacy of test articles for hepatic inflammation and fibrosis in mice.
ORGANISM
Mouse
STRAIN
C57BL/6
ASSAY INFORMATION
ASSAY TYPE
In Vivo
FUNCTIONAL MODE
Antagonist
DETECTION METHOD
Blood chemistry measurement
MEASURED RESPONSE
ALT/AST detection
TESTING INFORMATION
PROCEDURE SUMMARY
Groups of 8 male C57BL/6 mice at 8-10 weeks of age are used. Mice are fed choline-deficient, amino acid-defined high-fat diet (CDAHFD) or normal diet for 12 weeks. Vehicle and test articles are administered by oral gavage (PO) once daily during the 12 weeks of diet feeding. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are determined for evaluation of hepatic impairment by automated biochemical analyzer (TBA-120 FR, Toshiba, Japan) on Days 14, 28, 42, 56, 70 and 84. At the termination of the study (Day 84), animals are sacrificed 24 hours after the final treatment and the livers are harvested and weighed. Liver-to-body weight ratio is then calculated for each animal according to the formula: Liver (g)/BW x 100. Half of liver is snap frozen in liquid N2 for further cytokine analysis (optional), and the remaining 1/2 portion is formalin-fixed for histopathology (optional).
CRITERIA FOR SIGNIFICANCE
ANOVA and Dunnett’s test are used to ascertain difference between vehicle control and treated mice. Significance is set at p<0.05 level.
TURNAROUND TIME
STANDARD
120 Days
REFERENCE COMPOUND DATA
PUBCHEM ID NAME CONC CONC UNIT MEASUREMENT
4829Pioglitazone 30 mg/kg
CLINICAL RELEVANCE
THERAPEUTIC AREA
Metabolic Diseases
ADDITIONAL INFORMATION
BRAND
PDS
TESTING LOCATION
Taiwan - Taipei
OTHER INFORMATION
We will readily accommodate client-specified alterations. These studies are performed at our AAALAC accredited BSL-2 laboratory in Taipei, Taiwan. All aspects of this work are performed in general accordance with the Guide for the Care and Use of laboratory animals (National Academy Press, Washington, DC, 2011). The study protocol was approved by the Pharmacology Discovery Services IACUC and is performed with the oversight of veterinarians to assure the humane treatment of laboratory animals.

 

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