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Biomarker evaluation of skeletal muscle toxicity following clofibrate administration in rats.
Exp Toxicol Pathol 2016; 68(5):289-99ET

Abstract

The use of sensitive biomarkers to monitor skeletal muscle toxicity in preclinical toxicity studies is important for the risk assessment in humans during the development of a novel compound. Skeletal muscle toxicity in Sprague Dawley Rats was induced with clofibrate at different dose levels for 7 days to compare standard clinical pathology assays with novel skeletal muscle and cardiac muscle biomarkers, gene expression and histopathological changes. The standard clinical pathology assays aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK) enzyme activity were compared to novel biomarkers fatty acid binding protein 3 (Fabp3), myosin light chain 3 (Myl3), muscular isoform of CK immunoreactivity (three isoforms CKBB, CKMM, CKMB), parvalbumin (Prv), skeletal troponin I (sTnI), cardiac troponin T (cTnT), cardiac troponin I (cTnI), CKMM, and myoglobin (Myo). The biomarker elevations were correlated to histopathological findings detected in several muscles and gene expression changes. Clofibrate predominantly induced skeletal muscle toxicity of type I fibers of low magnitude. Useful biomarkers for skeletal muscle toxicity were AST, Fabp3, Myl3, (CKMB) and sTnI. Measurements of CK enzyme activity by a standard clinical assay were not useful for monitoring clofibrate-induced skeletal muscle toxicity in the rat at the doses used in this study.

Authors+Show Affiliations

Abbvie Deutschland GmbH & Co. KG, Preclinical Safety, D-67061 Ludwigshafen, Germany. Electronic address: karen.bodie@abbvie.com.Abbvie Inc., Discovery, Abbott Park, IL 60064, USA.Abbvie Deutschland GmbH & Co. KG, Preclinical Safety, D-67061 Ludwigshafen, Germany.Abbvie Inc., Discovery, Abbott Park, IL 60064, USA.Abbvie Deutschland GmbH & Co. KG, Preclinical Safety, D-67061 Ludwigshafen, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27020044

Citation

Bodié, Karen, et al. "Biomarker Evaluation of Skeletal Muscle Toxicity Following Clofibrate Administration in Rats." Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Fur Toxikologische Pathologie, vol. 68, no. 5, 2016, pp. 289-99.
Bodié K, Buck WR, Pieh J, et al. Biomarker evaluation of skeletal muscle toxicity following clofibrate administration in rats. Exp Toxicol Pathol. 2016;68(5):289-99.
Bodié, K., Buck, W. R., Pieh, J., Liguori, M. J., & Popp, A. (2016). Biomarker evaluation of skeletal muscle toxicity following clofibrate administration in rats. Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Fur Toxikologische Pathologie, 68(5), pp. 289-99. doi:10.1016/j.etp.2016.03.001.
Bodié K, et al. Biomarker Evaluation of Skeletal Muscle Toxicity Following Clofibrate Administration in Rats. Exp Toxicol Pathol. 2016;68(5):289-99. PubMed PMID: 27020044.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Biomarker evaluation of skeletal muscle toxicity following clofibrate administration in rats. AU - Bodié,Karen, AU - Buck,Wayne R, AU - Pieh,Julia, AU - Liguori,Michael J, AU - Popp,Andreas, Y1 - 2016/03/25/ PY - 2016/01/26/received PY - 2016/03/02/accepted PY - 2016/3/30/entrez PY - 2016/3/30/pubmed PY - 2017/1/12/medline KW - Clofibrate KW - Gene expression KW - Rat KW - Skeletal muscle biomarker SP - 289 EP - 99 JF - Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie JO - Exp. Toxicol. Pathol. VL - 68 IS - 5 N2 - The use of sensitive biomarkers to monitor skeletal muscle toxicity in preclinical toxicity studies is important for the risk assessment in humans during the development of a novel compound. Skeletal muscle toxicity in Sprague Dawley Rats was induced with clofibrate at different dose levels for 7 days to compare standard clinical pathology assays with novel skeletal muscle and cardiac muscle biomarkers, gene expression and histopathological changes. The standard clinical pathology assays aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK) enzyme activity were compared to novel biomarkers fatty acid binding protein 3 (Fabp3), myosin light chain 3 (Myl3), muscular isoform of CK immunoreactivity (three isoforms CKBB, CKMM, CKMB), parvalbumin (Prv), skeletal troponin I (sTnI), cardiac troponin T (cTnT), cardiac troponin I (cTnI), CKMM, and myoglobin (Myo). The biomarker elevations were correlated to histopathological findings detected in several muscles and gene expression changes. Clofibrate predominantly induced skeletal muscle toxicity of type I fibers of low magnitude. Useful biomarkers for skeletal muscle toxicity were AST, Fabp3, Myl3, (CKMB) and sTnI. Measurements of CK enzyme activity by a standard clinical assay were not useful for monitoring clofibrate-induced skeletal muscle toxicity in the rat at the doses used in this study. SN - 1618-1433 UR - https://www.unboundmedicine.com/medline/citation/27020044/Biomarker_evaluation_of_skeletal_muscle_toxicity_following_clofibrate_administration_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0940-2993(16)30020-3 DB - PRIME DP - Unbound Medicine ER -