Preventive effects of bortezomib on denervation-induced atrophy of the intrinsic laryngeal muscles: an experimental study in the rat.

CONCLUSION

Bortezomib was effective in attenuating atrophy of the posterior cricoarytenoid (PCA) muscle, but not the thyroarytenoid (TA) muscle. This was probably due to differences in the fiber composition of the two muscles. The PCA muscle is composed of a combination of fast- and slow-twitch fibers, and therefore is more resistant to atrophy than the TA muscle, which is composed solely of fast-twitch fibers.

OBJECTIVES

To investigate the preventive effects of bortezomib on denervation-induced atrophy of the TA and PCA muscles in the rat.

METHODS

Following transection of the left recurrent laryngeal nerve, bortezomib (100 μg/kg) was administered subcutaneously on post-denervation days 1 and 4, followed by a 10-day rest period every 14 days; each 2-week period constituted a single treatment cycle. In controls, saline was administered instead. Animals were killed for histological examination at 4 (n = 6), 8 (n = 7), and 12 (n = 7) weeks post-denervation. Muscle atrophy was assessed using three indices: wet muscle weight, muscle fiber cross-sectional area, and the number of muscle fibers/mm(2). The effects of bortezomib were evaluated by comparing the left (L) and right (R) muscles, with sequential changes in the L/R ratio assessed.

RESULTS

In saline-administered animals, atrophy of the left-sided TA and PCA muscles progressed rapidly during the first 4 weeks post-denervation, following which progression slowed. Atrophy was greater in the TA compared with the PCA muscle, although this difference was not statistically significant. In bortezomib-administered animals, atrophy of the PCA muscle was attenuated significantly at post-denervation weeks 8 and 12; no such reduction in atrophy was observed for the TA muscle.