Effects of a VEGFR-2 Inhibitor on Liver Enzyme Activity in Rats
Author Information
Author(s): Carmen Fuentealba, Monali Bera, Bart Jessen, Fred Sace, Greg J Stevens, Dusko Trajkovic, Amy H Yang, Winston Evering
Primary Institution: Pfizer Inc.
Hypothesis
Does the VEGFR-2 inhibitor AG28262 affect alanine aminotransferase (ALT) gene expression and activity in the liver of rats?
Conclusion
The VEGFR-2 inhibitor AG28262 increases serum ALT levels due to gene up-regulation without causing morphological changes in the liver.
Supporting Evidence
- ALT activity was significantly elevated on day 3 and further increased on day 8.
- ALT gene expression in the caudate lobe was significantly up-regulated by 63%.
- Statistically significant increased liver ALT enzymatic activity occurred in the caudate (96%) and right medial (41%) lobes.
Takeaway
This study found that a drug can raise liver enzyme levels without hurting the liver itself, which is important for understanding how drugs can affect the body.
Methodology
Sixteen female Sprague-Dawley rats were divided into control and treated groups, with the treated group receiving a VEGFR-2 inhibitor for 7 days, followed by evaluation of serum ALT activity and gene expression.
Limitations
The study was limited to a small sample size and only female rats, which may not represent broader populations.
Participant Demographics
Female Sprague-Dawley rats, weighing between 220-250 grams.
Statistical Information
P-Value
p < 0.01
Statistical Significance
p < 0.01
Digital Object Identifier (DOI)
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