In Vivo Treatment With The Nf-Kappa B Inhibitor Ursodeoxycholic Acid (Udca) Improves Tension Development In The Isolated Mdx Costal Diaphragm

Introduction: Previous experiments have indicated that in vivo administration of ursodeoxycholic acid (UDCA) inhibits nuclear NF-kappa B activation and has beneficial effects on the structure and function of dystrophic (mdx) muscle. We examined the effect of UDCA on tension development in dystrophic muscle. Methods: Isometric tension development was examined in costal diaphragms that were freshly isolated from vehicle and UDCA treated mdx mice. Percent recovery scores were obtained by directly comparing these measurements to those obtained from age-matched nondystrophic mice. Results: Vehicle treated mdx mice exhibited significantly reduced optimal muscle lengths (l(o)) and specific twitch and tetanic tensions compared with age-matched nondystrophic mice. UDCA treated preparations exhibited significantly improved tension development with a 33% recovery score. Conclusions: Because UDCA is used in treating certain clinical disorders, these results provide a rationale for human clinical trials using this and related drugs for treatment of Duchenne and related muscular dystrophies.