Eur Rev Med Pharmacol Sci 2020; 24 (5): 2683-2691

DOI: 10.26355/eurrev_202003_20538

Necrosulfonamide (NSA) protects intervertebral disc degeneration via necroptosis and apoptosis inhibition

Q.-X. Zhang, D. Guo, F.-C. Wang, W.-Y. Ding

Department of Spine Surgery, the Third Hospital of HeBei Medical University, Shijiazhuang, China. doctors2014@163.com


OBJECTIVE: Previous studies have shown that nucleus pulposus (NP) cell death plays an extremely important role in the progress of intervertebral disc degeneration (IVDD). This research aimed to investigate the protective effect of the MLKL inhibitor necrosulfonamide (NSA) on human NP cells.

PATIENTS AND METHODS: We collected human NP tissues from the patients undergoing disc herniation operations and isolated NP cell from the samples. IL-1β (10 ng/ml) was used to establish a NP cells degenerated model. We analyzed the expression of caspase 3, caspase 8, RIPK1, RIPK 3, and MLKL in different degree of degenerate disc tissues. Cell viability was analyzed by the Cell Counting Kit-8 (CCK-8) assay. The expression levels of collagen Ⅱ, β-galactosidase (β-gal), caspase 3, caspase 8, RIPK1, RIPK 3, and MLKL, several inflammatory and anti-oxidant enzymes of different NP cell treat groups were detected by Western blotting, immunofluorescence staining, or RT-PCR. Flow cytometry was used to measure the ROS level and cell apoptosis.

RESULTS: The data showed that expression of caspase 3, caspase 8, RIPK1, RIPK 3, and MLKL markedly increased in severely degenerated disc tissues. IL-1β promoted the cell death of NP cells, while NSA could reverse the effects of IL-1β. We found that NAS increased the antioxidant SOD1, SOD2, CAT, and GPX3 expression and suppressed oxidative stress in the disc. Moreover, MMP3, MMP10, IL-6, and TNF-α were significantly suppressed by the NSA.

CONCLUSIONS: These results suggest that NSA prevented NP degradation via inhibiting apoptosis and necroptosis of NP cells. Besides, the protective function of antagonizing cell death may owe to the inflammation and oxidative stress suppression.

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To cite this article

Q.-X. Zhang, D. Guo, F.-C. Wang, W.-Y. Ding
Necrosulfonamide (NSA) protects intervertebral disc degeneration via necroptosis and apoptosis inhibition

Eur Rev Med Pharmacol Sci
Year: 2020
Vol. 24 - N. 5
Pages: 2683-2691
DOI: 10.26355/eurrev_202003_20538