The utility of monitoring skeletal muscle troponin I to detect drug‐ induced skeletal muscle injury

Abstract

Drug‐induced myotoxicity is a continuing problem. Available myotoxicity biomarkers are of limited value. Recently, novel assays were developed to detect the slow and fast isoforms of skeletal muscle troponin (sTnI) released from type I (fast sTnI) and type II (slow sTnI) muscle fibers. The present study, using this assay, sought to determine whether monitoring serum levels of sTnI provided a better means to identify myotoxicity. Adult male or female Sprague‐Dawley rats were dosed with 25, 50 or 75 μ mole/kg 2, 3, 5, 6 tetramethyl p‐phenylenediamine (TMP) (sc) daily for 2 days or a single 200 mg/kg dose of cyclophosphamide (CP) (ip). Female rats were more sensitive to the toxic effects of TMP (mortality and body weight). Degenerative skeletal muscle changes were observed in both male and female rats. Increases in fast sTnI were noted in both male and female rats treated with 25 (2/5 male (avg 6 ng/ml) vs 3/5 female (avg 20 ng/ml) and in all animals given 50 μ moles/kg or higher. The levels of fast sTnI were significantly higher in female than male rats at the 50 μ mole/kg dose (avg 503 vs 64 ng/ml). Low levels of slow sTnI were detected in both female (25 and 50 μmole/kg) and male (75 μmole/kg). CK levels were increased over baseline only at the highest tolerated doses. No changes were noted in CP‐treated rats. Thus, sTnI appears to be a sensitive biomarker that could be used to detect drug‐induced myotoxicity.