Melatonin improves muscle function of the dystrophic mdx5Cv mouse, a model for Duchenne muscular dystrophy
Article first published online: 12 APR 2011
© 2011 John Wiley & Sons A/S
Journal of Pineal Research
Volume 51, Issue 2, pages 163–171, September 2011
How to Cite
Hibaoui, Y., Reutenauer-Patte, J., Patthey-Vuadens, O., Ruegg, U. T. and Dorchies, O. M. (2011), Melatonin improves muscle function of the dystrophic mdx5Cv mouse, a model for Duchenne muscular dystrophy. Journal of Pineal Research, 51: 163–171. doi: 10.1111/j.1600-079X.2011.00871.x
- Issue published online: 10 AUG 2011
- Article first published online: 12 APR 2011
- Accepted manuscript online: 25 FEB 2011 10:39AM EST
- Received November 17, 2010; Accepted February 18, 2011.
- Duchenne muscular dystrophy;
- mdx mouse;
- oxidative stress
Abstract: Duchenne muscular dystrophy (DMD) is a severe X-linked muscle-wasting disease caused by the absence of the cytoskeletal protein dystrophin. In addition to abnormal calcium handling, numerous studies point to a crucial role of oxidative stress in the pathogenesis of the disease. Considering the impressive results provided by antioxidants on dystrophic muscle structure and function, we investigated whether melatonin can protect the mdx5Cv mouse, an animal model for DMD. Male mdx5Cv mouse pups were treated with melatonin by daily intraperitoneal (i.p.) injection (30 mg/kg body weight) or by subcutaneous (s.c.) implant(s) (18 or 54 mg melatonin as Melovine® implants) from 17/18 to 28/29 days of age. Isometric force of the triceps surae was recorded at the end of the treatment. The i.p. treatment increased the phasic twitch tension of mdx5Cv mice. The maximal tetanic tension was ameliorated by 18 mg s.c. and 30 mg/kg i.p. treatments. Melatonin caused the dystrophic muscle to contract and relax faster. The force–frequency relationship of melatonin-treated dystrophic mice was shifted to the right. In accordance with improved muscle function, melatonin decreased plasma creatine kinase activity, a marker for muscle injury. Melatonin treatment increased total glutathione content and lowered the oxidized/reduced glutathione ratio, indicating a better redox status of the muscle. In light of the present investigation, the therapeutic potential of melatonin should be further considered for patients with DMD.