The cysteine precursor L‐2‐oxothiazolidine‐4‐carboxylate does not delay diaphragm fatigue in vitro

Abstract

Metabolism of L‐2‐oxothiazolidine‐4‐carboxylate (OTC; Procysteine®) by 5‐oxoprolinase promotes intracellular cysteine and glutathione synthesis. The latter are important antioxidants in muscles. Therefore, we hypothesized that OTC would inhibit fatigue of diaphragm in vitro. Diaphragm strips from adult male ICR mice (n = 14) were incubated for 1 hr at 37 ºC with buffer (control, C) or OTC (10 mM) in an organ chamber. One min after completing a standardized force‐frequency protocol, muscles were stimulated (50 Hz, 500 ms train duration) every 2 s for 10 min. Force was measured at the onset and end of the fatigue trial. A fatigue index was calculated as the ratio of final‐to‐initial force. Data are presented as mean ± sem. Force developed at the onset of the fatigue protocol (C = 12.3 ± 2.3 N/cm2, OTC = 11.3 ± 1.5 N/cm2; p = 0.30) and the fatigue index (C = 0.43 ± 0.03, OTC = 0.51 ± 0.06; p = 0.45) were not different between control and OTC‐treated muscles. These results show that 10 mM OTC does not diminish diaphragm fatigue in vitro, and suggest that OTC may not be an effective treatment for muscle fatigue in vivo.Financial Support: AHA Postdoctoral Fellowship (0725334B) and NASA/NSBRI (MA00209)