Skeletal muscle troponin I as a biomarker of skeletal muscle injury

Abstract

Many classes of drugs induce SM injury and creatine kinase (CK) has been used as a biomarker to detect this injury. The present study utilized an ultrasensitive immunoassay (Errena) to determine if slow or fast‐twitch troponin I (ssTnI, fsTnI) would be more useful biomarkers. Sprague‐Dawley (SD) rats (N=27, ♀, 12 wks) were dosed (po) with Simvastatin (SVS) (80 mg/kg) or water (n=15) once a day for up to 14 days. Tissues and blood samples were collected 24 hrs after final dosing. Fifteen SD dosed for 6‐11days were euthanized early (ED) due to excessive weight loss. SVS SM injury was detected in 9 ED animals (primarily in the psoas muscle (9/9)and multiple muscles in 3/9). All 15 had elevated levels of fsTnI. The 9 SD with muscle injury (lesion score>1.0) had higher mean levels (4691 pg/ml) compared to (651 pg/ml) in the remaining 6 ED animals and 129 pg/ml in15 control SD. SVS SM injury was absent in the Soleus muscle and ssTnI increased in only 1 of 15 ED. The levels of CK were not consistent. SVS SM injury was present in 5 of 12 SD that were treated for 14D (TS). Lesions were consistently present in the psoas muscle (5/5) and in multiple muscles in 3/5 TS rats. Serum levels of fsTnI were elevated 5 SD with lesions (8,317 pg/ml) and were normal in 7 unaffected TS SD (147 pg/ml). Microscopic SVS SM injury was absent in the Soleus muscle and ssTnI levels frrm all 12 SD were normal (156 pg/ml). CK levels increased from 199 IU (no lesions) to 526 IU (psoas lesions). These results suggest ssTnI and fsTnI are usefull biomarkers to identify drug‐affected SM fiber types and may offer advantages over routine microscopic evaluation or CK.