Fexofenadine Protects Against Intervertebral Disc Degeneration Through TNF Signaling

Abstract

<b>Objective:</b> Fexofenadine (FFD) is an antihistamine drug with an anti-inflammatory effect. The intervertebral disc (IVD) degeneration process is involved in inflammation in which tumor necrosis factor-α (TNF-α) plays an important role. This study aims to investigate the role of FFD in the pathological process of IVD degeneration. <b>Methods:</b> Safranin O staining was used for the measurement of cartilageous tissue in the disc. Hematoxylin-Eosin (H&E) staining was used to determine the disc construction. A rat needle puncture model was taken advantage of to examine the role of FFD in disc degeneration <i>in vivo</i>. Western Blotting assay, immunochemistry, and immunoflurence staining were used for the determination of inflammatory molecules. ELISA assay was performed to detect the release of inflammatory cytokines. A real-time PCR assay was analyzed to determine the transcriptional expressions of molecules. <b>Results:</b> Elevated TNF-α resulted in inflammatory disc degeneration, while FFD protected against TNF-α-induced IVD degeneration. Mechanism study found FFD exhibited a disc protective effect through at least two pathways. (a) FFD inhibited TNF-α-mediated extracellular matrix (ECM) degradation and (b) FFD rescued TNF-α induced inflammation in disc degeneration. Furthermore, the present study found that FFD suppressed TNF-α mediated disc degeneration via the cPLA2/NF-κB signaling pathway. <b>Conclusions:</b> FFD provided another alternative for treating disc degeneration through a novel mechanism. Additionally, FFD may also be a potential target for the treatment of other inflammatory-related diseases, including IVD degeneration.