RESUMEN
The objective of this study was to investigate the effects of doxycycline, a broad-spectrum MMP inhibitor, on cage activity and exercised supraspinatus tendon and muscle using a Sprague-Dawley rat model of non-injurious exercise. Because exercise may alter muscle and tendon MMP activity and matrix turnover, we hypothesized that doxycycline would abolish the beneficial adaptations found with exercise but have no effect on cage activity muscle and tendon properties. Rats were divided into acute or chronic exercise (EX) or cage activity (CA) groups, and half of the rats received doxycycline orally. Animals in acute EX groups were euthanized 24â¯h after a single bout of exercise (10â¯m/min, 1â¯h) on a flat treadmill. Animals in chronic EX groups walked on a flat treadmill and were euthanized at 2 or 8â¯week time points. Assays included supraspinatus tendon mechanics and histology and muscle fiber morphologic and type analysis. Doxycycline improved tendon mechanical properties and collagen organization in chronic cage activity groups, which was not consistently evident in exercised groups. Combined with exercise, doxycycline decreased average muscle fiber cross-sectional area. Results of this study suggest that administration of doxycycline at pharmaceutical doses induces beneficial supraspinatus tendon adaptations without negatively affecting the muscle in cage activity animals, supporting the use of doxycycline to combat degenerative processes associated with underuse; however, when combined with exercise, doxycycline does not consistently produce the same beneficial adaptations in rat supraspinatus tendons and reduces muscle fiber cross-sectional area, suggesting that doxycycline is not advantageous when combined with activity.
Asunto(s)
Antibacterianos/farmacología , Doxiciclina/farmacología , Fibras Musculares Esqueléticas/efectos de los fármacos , Tendones/efectos de los fármacos , Adaptación Fisiológica , Animales , Fenómenos Biomecánicos , Colágeno/fisiología , Masculino , Fibras Musculares Esqueléticas/fisiología , Condicionamiento Físico Animal/fisiología , Ratas Sprague-Dawley , Manguito de los Rotadores/efectos de los fármacos , Manguito de los Rotadores/fisiología , Tendones/fisiologíaRESUMEN
BACKGROUND: Previous studies have shown that ibuprofen is detrimental to tissue healing after acute injury; however, the effects of ibuprofen when combined with noninjurious exercise are debated. HYPOTHESIS: Administration of ibuprofen to rats undergoing a noninjurious treadmill exercise protocol will abolish the beneficial adaptations found with exercise but will have no effect on sedentary muscle and tendon properties. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 167 male Sprague-Dawley rats were divided into exercise or cage activity (sedentary) groups and acute (a single bout of exercise followed by 24 hours of rest) and chronic (2 or 8 weeks of repeated exercise) response times. Half of the rats were administered ibuprofen to investigate the effects of this drug over time when combined with different activity levels (exercise and sedentary). Supraspinatus tendons were used for mechanical testing and histologic assessment (organization, cell shape, cellularity), and supraspinatus muscles were used for morphologic (fiber cross-sectional area, centrally nucleated fibers) and fiber type analysis. RESULTS: Chronic intake of ibuprofen did not impair supraspinatus tendon organization or mechanical adaptations (stiffness, modulus, maximum load, maximum stress, dynamic modulus, or viscoelastic properties) to exercise. Tendon mechanical properties were not diminished and in some instances increased with ibuprofen. In contrast, total supraspinatus muscle fiber cross-sectional area decreased with ibuprofen at chronic response times, and some fiber type-specific changes were detected. CONCLUSION: Chronic administration of ibuprofen does not impair supraspinatus tendon mechanical properties in a rat model of exercise but does decrease supraspinatus muscle fiber cross-sectional area. This fundamental study adds to the growing literature on the effects of ibuprofen on musculoskeletal tissues and provides a solid foundation on which future work can build. CLINICAL RELEVANCE: The study findings suggest that ibuprofen does not detrimentally affect regulation of supraspinatus tendon adaptations to exercise but does decrease muscle growth. Individuals should be advised on the risk of decreased muscle hypertrophy when consuming ibuprofen.