1. Effects of hydroxyurea on skeletal muscle energetics and force production in a sickle cell disease murine model
- Author
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Constance P. Michel, David Bendahan, Benoit Giannesini, Christophe Vilmen, Yann Le Fur, Laurent A. Messonnier, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])
- Subjects
Physiology ,Physiology (medical) ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,[SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph] - Abstract
International audience; Hydroxyurea (HU) is commonly used as a treatment for patients with sickle cell disease (SCD) to enhance fetal hemoglobin production. This increased production is expected to reduce anemia (which depresses oxygen transport) and abnormal Hb content alleviating clinical symptoms such as vaso-occlusive crisis and acute chest syndrome. The effects of HU on skeletal muscle bioenergetics in vivo are still unknown. Due to the beneficial effects of HU upon oxygen delivery, improved skeletal muscle energetics and function in response to a HU treatment have been hypothesized. Muscle energetics and function were analyzed during a standardized rest-exercise-recovery protocol, using 31P-magnetic resonance spectroscopy in Townes SCD mice. Measurements were performed in three groups of mice: one group of 2-mo-old mice (SCD2m, n = 8), another one of 4-mo-old mice (SCD4m, n = 8), and a last group of 4-mo-old mice that have been treated from 2 mo of age with HU at 50 mg/kg/day (SCD4m-HU, n = 8). As compared with SCD2m mice, SCD4m mice were heavier and displayed a lower acidosis. As lower specific forces were developed by SCD4m compared with SCD2m, greater force-normalized phosphocreatine consumption and oxidative and nonoxidative costs of contraction were also reported. HU-treated mice (SCD4m-HU) displayed a significantly higher specific force production as compared with untreated mice (SCD4m), whereas muscle energetics was unchanged. Overall, our results support a beneficial effect of HU on muscle function.
- Published
- 2023