@article {Collier409, author = {Alyssa F. Collier and Jessica Gumerson and Kimmo Lehtim{\"a}ki and Jukka Puoliv{\"a}li and Jace W. Jones and Maureen A. Kane and Sankeerth Manne and Andrea O{\textquoteright}Neill and Hillarie P. Windish and Toni Ahtoniemi and Bradley A. Williams and Douglas E. Albrecht and Robert J. Bloch}, title = {Effect of Ibuprofen on Skeletal Muscle of Dysferlin-Null Mice}, volume = {364}, number = {3}, pages = {409--419}, year = {2018}, doi = {10.1124/jpet.117.244244}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Ibuprofen, a nonsteroidal 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 or α-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), a NO donor, to learn whether 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 day 3 postinjury, fiber necrosis, and macrophage infiltration at day 3 postinjury, 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 day 3 postinjury significantly decreased as a function of ibuprofen concentration in the serum (range, 0.67{\textendash}8.2 {\textmu}g/ml), independent of ISDN. The effects of ISDN on torque loss at day 3 postinjury 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.}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/364/3/409}, eprint = {https://jpet.aspetjournals.org/content/364/3/409.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }