• Hideyuki Kinoshita, Sumihisa Orita, Kazuhide Inage, Kazuyo Yamauchi, Koki Abe, Masahiro Inoue, Masaki Norimoto, Tomotaka Umimura, Yawara Eguchi, Kazuki Fujimoto, Yasuhiro Shiga, Hirohito Kanamoto, Yasuchika Aoki, Takeo Furuya, Miyako Suzuki, Tsutomu Akazawa, Kazuhisa Takahashi, and Seiji Ohtori.
• Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
• Spine. 2019 Apr 15; 44 (8): E446-E455.

Study DesignA basic study using a rodent model of sarcopenia.ObjectiveTo elucidate the contribution of oxidative stress to muscle degeneration and the efficacy of antioxidant treatment for sarcopenia using an animal model of neurogenic sarcopenia.Summary Of Background DataOxidative stress has been reported to be involved in a number of pathologies, including musculoskeletal disorders. Its relationship with sarcopenia, one of the potential origins of lower back pain, however, is not yet fully understood.MethodsMyoblast cell lines (C2C12) were treated with H2O2, an oxidative stress inducer, and N-acetyl-L-cysteine (NAC), an antioxidant. Apoptotic effects induced by oxidative stress and the antioxidant effects of NAC were assessed by western blotting, immunocytochemistry, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assays. An animal model of sarcopenia was produced via axotomy of the sciatic nerves to induce muscle atrophy. Twenty-four male Sprague-Dawley rats were divided into sham, sham+NAC, axotomy, and axotomy+NAC groups. Rats were provided water only or water containing NAC (1 g/L) for 4 weeks. The gastrocnemius muscle was isolated and stained with hematoxylin and eosin (H&E) 2 weeks after axotomy, from which muscle cells were harvested and protein extracted for evaluation.ResultsMitogen-activated protein kinases (MAPKs) were significantly activated by H2O2 treatment in C2C12 cells, which was ameliorated by NAC pretreatment. Furthermore, H2O2 induced apoptosis and death of C2C12 cells, which was prevented by NAC pretreatment. The weight of the gastrocnemius muscle was reduced in the axotomy group, which was prevented by NAC administration. Lastly, although muscle specimens from the axotomy group showed greater reductions in muscle fiber, the oral administration of NAC significantly inhibited amyotrophy via antioxidant effects.ConclusionThe current in vitro and in vivo study demonstrated the possible involvement of oxidative stress in sarcopenic pathology. NAC represents a potential anti-sarcopenic drug candidate, preventing amyotrophy and fatty degeneration.Level Of Evidence4.

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