Ibuprofen can have deleterious effects on dysferlin-null muscle. - GreenMedInfo Summary

Ibuprofen, a non-steroidal anti-inflammatory drug, and nitric oxide (NO) donors have been reported to reduce the severity of muscular dystrophies in mice associated with the absence of dystrophin orα-sarcoglycan, but their effects on mice that are dystrophic due to the absence of dysferlin have not been examined. We have tested ibuprofen, as well as isosorbide dinitrate (ISDN), an NO donor, to learn if used alone or together they protect dysferlin-null muscle in A/J mice from large strain injury (LSI) induced by a series of high strain lengthening contractions. Mice were maintained on chow containing ibuprofen and ISDN for 4 weeks. They were then subjected to LSI and maintained on the drugs for 3 additional days. We measured loss of torque immediately following injury and at d3 post-injury, fiber necrosis and macrophage infiltration at d3 post-injury, and serum levels of the drugs at the time of euthanasia. Loss of torque immediately after injury was not altered by the drugs. However, the torque on d3 post-injury significantly decreased as a function of ibuprofen concentration inthe serum (range, 0.67 - 8.2 µg/ml), independent of ISDN. The effects of ISDN on torque loss at d3 post-injury were not significant. In long term studies of dysferlinopathic BlAJ mice, lower doses of ibuprofen had no effects on muscle morphology but reduced treadmill running by 40%. Our results indicate that ibuprofen can have deleterious effects on dysferlin-null muscle and suggest that its use at pharmacological doses should be avoided by individuals with dysferlinopathies.