Safety & Pharmacokinetics, Central Research Laboratory, Research & Development, Seikagaku Corporation, Higashiyamato, Tokyo, Japan.
Toxicol Pathol. 2020 Jul;48(5):656-668. doi: 10.1177/0192623320928006.
Selective chemonucleolytic effects of condoliase, a glycosaminoglycan degrading enzyme, was investigated histopathologically in cynomolgus monkeys. Condoliase was administered once into the lumber intervertebral disc (IVD), and as a comparative control, chymopapain, a proteolytic enzyme, was administered in a similar manner. Histopathological changes of the IVD and the adjacent vertebral body (VB) were examined at 1 to 26 weeks after administration. Major changes induced by condoliase in the IVD were degenerative and necrotic changes in the nucleus pulposus, annulus fibrosus, cartilaginous endplate (CEP), and epiphyseal growth plate (EGP); focal disappearance of the EGP; and neovascularization and ossification of the CEP. Decreased/necrosis of bone marrow cells with new bone formation was observed in the VB. Cellular regeneration in the IVD was observed as a recovery changes on and after week 4. The changes in the IVD and VB subsided at week 26. Chymopapain induced qualitatively similar but more widely extended changes. The degrees of the changes in the IVD and VB were more severe than those of condoliase, and the changes were exacerbated even at week 26. These results indicated that histopathological changes caused by condoliase were less severe and more selective than those by chymopapain.
研究了糖苷水解酶(一种糖胺聚糖降解酶)在食蟹猴中的选择性化学核溶解作用。将 condoliase 一次性注入腰椎间盘(IVD),并作为对照,以类似的方式给予木瓜凝乳蛋白酶(一种蛋白水解酶)。给药后 1 至 26 周,检查 IVD 和相邻椎体(VB)的组织病理学变化。Condoliase 在 IVD 引起的主要变化是髓核、纤维环、软骨终板(CEP)和骺板生长板(EGP)的退行性和坏死性变化;EGP 的局灶性消失;CEP 的新生血管形成和骨化。在 VB 中观察到骨髓细胞减少/坏死和新骨形成。IVD 中的细胞再生在第 4 周及以后作为恢复变化出现。IVD 和 VB 的变化在第 26 周时消退。木瓜凝乳蛋白酶诱导的变化在性质上相似,但范围更广。IVD 和 VB 的变化比 condoliase 更严重,即使在第 26 周,这些变化也在加剧。这些结果表明,condoliase 引起的组织病理学变化比 chymopapain 引起的变化更轻微、更具选择性。