Back to Search
Start Over
Assessment of Preclinical Liver and Skeletal Muscle Biomarkers Following Clofibrate Administration in Wistar Rats.
- Source :
-
Toxicologic pathology [Toxicol Pathol] 2017 Jun; Vol. 45 (4), pp. 506-525. Date of Electronic Publication: 2017 May 09. - Publication Year :
- 2017
-
Abstract
- Clofibrate is a known rodent hepatotoxicant classically associated with hepatocellular hypertrophy and increased serum activities of cellular alanine aminotransferase/aspartate aminotransferase (ALT/AST) in the absence of microscopic hepatocellular degeneration. At toxic dose, clofibrate induces liver and skeletal muscle injury. The objective of this study was to assess novel liver and skeletal muscle biomarkers following clofibrate administration in Wistar rats at different dose levels for 7 days. In addition to classical biomarkers, liver injury was assessed by cytokeratin 18 (CK18) cleaved form, high-mobility group box 1, arginase 1 (ARG1), microRNA 122 (miR-122), and glutamate dehydrogenase. Skeletal muscle injury was evaluated with fatty acid binding protein 3 (Fabp3) and myosin light chain 3 (Myl3). Clofibrate-induced hepatocellular hypertrophy and skeletal muscle degeneration (type I rich muscles) were noted microscopically. CK, Fabp3, and Myl3 elevations correlated to myofiber degeneration. Fabp3 and Myl3 outperformed CK for detection of myofiber degeneration of minimal severity. miR-122 and ARG1 results were significantly correlated and indicated the absence of liver toxicity at low doses of clofibrate, despite increased ALT/AST activities. Moreover, combining classical and novel biomarkers (Fabp3, Myl3, ARG1, and miR-122) can be considered a valuable strategy for differentiating increased transaminases due to liver toxicity from skeletal muscle toxicity.
- Subjects :
- Alanine Transaminase blood
Alkaline Phosphatase blood
Animals
Anticholesteremic Agents administration & dosage
Arginase blood
Aspartate Aminotransferases blood
Bilirubin blood
Cholesterol blood
Cholinesterases blood
Clofibrate administration & dosage
Creatinine blood
Dose-Response Relationship, Drug
Fatty Acid Binding Protein 3 blood
Glutamate Dehydrogenase blood
Keratin-18 blood
Liver metabolism
Male
MicroRNAs blood
Muscle, Skeletal metabolism
Myosin Light Chains blood
Rats
Rats, Wistar
Triglycerides blood
Anticholesteremic Agents adverse effects
Biomarkers blood
Chemical and Drug Induced Liver Injury pathology
Clofibrate adverse effects
Liver drug effects
Muscle, Skeletal drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1533-1601
- Volume :
- 45
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Toxicologic pathology
- Publication Type :
- Academic Journal
- Accession number :
- 28485676
- Full Text :
- https://doi.org/10.1177/0192623317707271