Background: Spinal cord injury (SCI) can induce secondary damage, such as inflammation, oxidative stress, and neuronal cell death. These factors impede recovery. This study evaluated the therapeutic potential of tegoprazan (TEGO), a drug known to act via a potassium-competitive acid blocker, in a SCI rat model.

Methods: We conducted SCI in female rats, and TEGO was administered intraperitoneally. Methylprednisolone (MP) was used as a positive control. TEGO was dissolved in dimethyl sulfoxide (DMSO) and sonicated before injection. Toxicity was assessed by body weight monitoring, and motor recovery was assessed by behavioral tests. We performed immunofluorescence and qRT-PCR to investigate inflammatory markers. Western blot analyses were evaluated for mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways.

Results: TEGO treatment had no systemic toxicity and improved motor recovery. TEGO (p < 0.05) and MP (p < 0.01) decreased inducible nitric oxide synthase (iNOS) expression. CD206 expression was significantly increased in the MP group (p < 0.01) compared with the Vehicle group, whereas the TEGO group showed a slight increase compared with the Vehicle group. Furthermore, TEGO inhibited MAPK/NF-κB signaling, attenuating pro-inflammatory cytokine production.

Conclusions: TEGO, a representative potassium-competitive acid blocker (P-CABs), suppressed pro-inflammatory gene expression and might be applied as a novel treatment for SCI.