| First Author | Messina S | Year | 2006 |
| Journal | Am J Pathol | Volume | 168 |
| Issue | 3 | Pages | 918-26 |
| PubMed ID | 16507907 | Mgi Jnum | J:106560 |
| Mgi Id | MGI:3618969 | Doi | 10.2353/ajpath.2006.050673 |
| Citation | Messina S, et al. (2006) Lipid peroxidation inhibition blunts nuclear factor-kappaB activation, reduces skeletal muscle degeneration, and enhances muscle function in mdx mice. Am J Pathol 168(3):918-26 |
| abstractText | Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease resulting from lack of the sarcolemmal protein dystrophin. However, the mechanism leading to the final disease status is not fully understood. Several lines of evidence suggest a role for nuclear factor (NF)-kappaB in muscle degeneration as well as regeneration in DMD patients and mdx mice. We investigated the effects of blocking NF-kappaB by inhibition of oxidative stress/lipid peroxidation on the dystrophic process in mdx mice. Five-week-old mdx mice received three times a week for 5 weeks either IRFI-042 (20 mg/kg), a strong antioxidant and lipid peroxidation inhibitor, or its vehicle. IRFI-042 treatment increased forelimb strength (+22%, P < 0.05) and strength normalized to weight (+23%, P < 0.05) and decreased fatigue (-45%, P < 0.05). It also reduced serum creatine kinase levels (P < 0.01) and reduced muscle-conjugated diene content and augmented muscle-reduced glutathione (P < 0.01). IRFI-042 blunted NF-kappaB DNA-binding activity and tumor necrosis factor-alpha expression in the dystrophic muscles (P < 0.01), reducing muscle necrosis (P < 0.01) and enhancing regeneration (P < 0.05). Our data suggest that oxidative stress/lipid peroxidation represents one of the mechanisms activating NF-kappaB and the consequent pathogenetic cascade in mdx muscles. Most importantly, these new findings may have clinical implications for the pharmacological treatment of patients with DMD. |
