Antioxidant treatment with vitamin C attenuated rotator cuff degeneration caused by oxidative stress in Sod1-deficient mice

Background Rotator cuff degeneration is 1 of several factors that lead to rotator cuff tears; however, the mechanism of this degeneration remains unclear. We previously reported that deficiency of an antioxidant enzyme, superoxide dismutase 1 ( Sod1 ), in mice induced degeneration in supraspinatus tendon entheses, a model that replicates human rotator cuff degeneration. In this study, we analyzed possible effects of vitamin C (VC), a major antioxidant, on the degenerative changes of supraspinatus entheses in Sod1 −/− mice. Methods We administered VC or vehicle, distilled water, for 8 weeks to Sod1 −/− and wild-type male mice beginning at 12 weeks of age (n = 5-8 per group). When mice were 20 weeks of age, we sectioned rotator cuff tissue samples and performed hematoxylin-eosin and toluidine blue staining for quantitative histologic evaluation. Results VC administration, compared with vehicle administration, attenuated the histologic changes, including a misaligned 4-layered structure, fragmented tidemark, and toluidine blue staining, in the supraspinatus entheses of Sod1 −/− mice. In the quantitative histologic evaluation, all parameters were significantly decreased in Sod1 −/− mice compared with wild-type mice, except for the number of nonchondrocytes. Conclusion We demonstrated that an antioxidant treatment, VC administration, attenuated the rotator cuff degeneration, similar to that observed in humans, that is caused by oxidative stress in Sod1 −/− mice. VC effects included improvements in quantitative histologic parameters and other histologic changes. These results suggest that VC treatment can prevent oxidative stress–induced degeneration of the rotator cuff.