Evaluation of the usefulness of biomarkers for cardiac and skeletal myotoxicity in rats.

Tonomura, Y., Mori, Y., Torii, M., Uehara, T.
Journal   Toxicology.
Species  
Analytes Measured   Troponin I cardiac , Troponin T cardiac , FABP3 , Myl3
Matrix Tested   Serum
Year   2009
Volume   266
Page Numbers   48-54
Application   Toxicology
Abstract
Since cardiac and skeletal myotoxicity affect the development of drug candidates, it is important to detect their toxicity at an early stage of drug development. For that purpose, in this study, the usefulness of several cardiac and skeletal myotoxic biomarkers in blood were evaluated using two rat models treated intraperitoneally with an acetylcholinesterase inhibitor carbofuran (CAF) or a synthetic catecholamine isoproterenol (ISO). The biomarkers assayed were fatty acid binding protein 3 (Fabp3), myosin light chain 1 (MLC1), cardiac troponin I (cTnI), cardiac troponin T (cTnT), aspartate transaminase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK). CAF and ISO treatment of rats induced greater increases in the levels of Fabp3, MLC1, cTnI and cTnT than in the levels of AST, LDH and CK. A kinetic analysis indicated that the levels of all of the biomarkers had returned to the basal level by 24h after drug administration. Pathological examination revealed lesions in the heart, mainly at the left ventricle and septum, in both CAF- and ISO-treated rats. CAF-treated rats showed widespread lesions of skeletal muscle that were independent of muscle fiber type, while in ISO-treated rats locoregional lesions were observed only in slow twitch muscle. Receiver operating characteristic curve analysis of the sensitivity of the tested biomarkers indicated that MLC1 and cTnT were the most effective biomarkers of cardiotoxicity. For skeletal myotoxicity, Fabp3 and MLC1 were the most effective biomarkers based on the specific tissue distribution of these proteins. Conversely, the rapid blood clearance of these markers should be taken into account when considering the use of these biomarkers.

View Publications

Related Products

R-PLEX Human Troponin T Cardiac Antibody Set
Troponin T (cardiac) | Human
Singleplex
R-PLEX Human FABP3/H-FABP Antibody Set
FABP3/H-FABP | Human
Singleplex
Human FABP3 Kit
FABP3/H-FABP | Human
Singleplex
Muscle Injury Panel 3 Mouse Kit
cTroponin I, FABP3/H-FABP, Myl3/CMLC1, Troponin I (fast-twitch) | Mouse
Multiplex
Muscle Injury Panel 1 Rat Kit
cTroponin I, FABP3/H-FABP, Myl3/CMLC1, Troponin I (fast-twitch), Troponin T (cardiac) | Rat
Multiplex
Rat Cardiac Troponin ITC Complex Kit
cTroponin I, Troponin ITC Complex | Rat
Singleplex
Cardiac Injury Panel 2 Rat Kit
cTroponin I, FABP3/H-FABP, Troponin T (cardiac) | Rat
Multiplex
Cardiac Injury Panel 3 Rat Kit
cTroponin I, FABP3/H-FABP, Myl3/CMLC1, Troponin T (cardiac) | Rat
Multiplex
Browse Our Products

By Analytes
By Applications
Search
Customer Service/Orders


Scientific/Technical Support


Instrument Support


Company Headquarters