Serum miR-206 as a biomarker for drug-induced skeletal muscle injury in rats.
JOURNAL OF TOXICOLOGICAL SCIENCES(2020)
摘要
Creatine kinase (CK) and lactate dehydrogenase (LDH) serve as biomaricers for skeletal muscle injury in preclinical toxicity studies, but have a limitation regarding tissue specificity. Circulating miR-206 was recently reported to be a useful biomarker for skeletal muscle disorders in humans. Here, we sought to determine whether serum miR-206 can be used as a biomarker in preclinical toxicity studies to detect drug-induced skeletal muscle injury with higher sensitivity and specificity than the biomarkers CK. LDH, skeletal troponin I (sTnI), and myosin light chain 3 (My13). We established rat models of skeletal muscle injury through treatment with the muscle toxicant 2,3,5,6-tetramethyl-p-phenylenediamine (TMPD) as well as four in-house compounds. We found that serum miR-206 levels significantly increased after treatment with TMPD, and tended to be higher in rats treated with in-house compounds than in control rats. ROC analysis revealed that the specificity of serum miR-206 for detection of skeletal muscle injury was higher compared with those of other markers. Further, serum miR-206 levels were unchanged in rats with isoproterenol-induced cardiotoxicity. These findings demonstrate that serum miR-206 may serve as a highly specific biomarker for preclinical analysis of rats with drug-induced skeletal muscle injuries.
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关键词
Circulating miRNA,Biomarker,Skeletal muscle injury
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