Studies with Skeletal Muscle Troponin I (sTnI), a New Biomarker of Skeletal Muscle Injury

Abstract

Available biomarkers of myotoxicity such as creatine kinase (CK), are of limited value. Recently, new assays (Pathway Diagnostics) have been developed which can detect the slow and fast isoforms of skeletal muscle troponin I (sTnI). This study evaluated the use of sTnI as a biomarker to detect alterations induced by a known skeletal muscle toxicant (2, 3, 5, 6 tetramethyl p‐phenylenediamine,TMP). Adult male and female Wistar(W) and Sprague Dawley rats(SD)(5 rats/group) were dosed with 25, 50 or 75 µmole/kg (sc) daily for 2 days or 200 mg/kg cyclophosphamide (CP)(1day) (ip). Tissues were collected 24 hrs(TMP) or 48 hrs (CP) after dosing. Rats given CP had normal muscle morphology and no detectable sTnI. Female rats were more sensitive to TMP (mortality vs males). TMP‐induced patchy muscle necrosis with inflammation. Increases in fast sTnI were noted in male (2/5) and female (3/5) SD rats treated with 25 µmole/kg TMP (male avg 31 ng/ml vs female avg 65 ng/ml). At 50 µmole/kg all animals had increased levels of fast sTnI. The levels of fast sTnI were significantly higher in female SD than male SD rats at the 50 µmole/kg dose (avg 2354 vs 347 ng/ml). Low levels of slow sTnI were detected in both female (25 and 50 µmole/kg) and male (75 µmole/kg) SD rats. CK levels were increased over baseline only at the highest tolerated doses. Thus, sTnI appears to be a sensitive biomarker that could be used to detect chemically‐induced myotoxicity.