Plasma triglycerides: an overlooked biomarker of hepatotoxicity in the rat

• Published in: Comparative clinical pathology Vol. 12; no. 2; pp. 95 - 101
• Main Authors: Provost, J.P., Hanton, G., Net, J.L. Le
• Format: Journal Article
• Language: English
• Published: London Springer Nature B.V 01.09.2003
• Subjects: Diet; Plasma; Rodents; Triglycerides
• ISSN: 1618-5641; 1618-565X
• DOI: 10.1007/s00580-003-0483-1

The usefulness of plasma triglycerides as a biomarker for hepatotoxicity in the rat was assessed using reference hepatotoxicants. Groups of rats received a single dose of each compound (allyl formate, chlorpromazine, ethionine, galactosamine, thioacetamide, rifampicin and WY-14,643) at two dose levels selected from data in the literature. Body weight and clinical signs were recorded. A blood sample was taken 24 h after dosing for triglyceride determination, as well as a complete list of plasma chemistry parameters. The rats were then subjected to histopathology of the liver. All compounds decreased plasma triglycerides at amplitudes ranging from slight to marked, and induced various histopathological changes in the liver. Although the mechanisms involved are still not completely understood, it is felt that these decreases in triglycerides are metabolic counterparts of an intrinsic toxicity most probably involving an increase in the catabolism of lipids, an impairment of their synthesis, or transportation associated with effects on VLDL particles. Therefore, we conclude that the concentration of circulating triglycerides may be an early and reliable indicator of hepatotoxicity in the rat and we recommend its assessment as a part of the core list of liver parameters in preclinical studies.[PUBLICATION ABSTRACT]