Fexofenadine Protects Against Intervertebral Disc Degeneration Through TNF Signaling

Abstract

Objective: 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.Methods: 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 in vivo. 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.Results: 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.Conclusions: 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.

Oxidative Stress in Intervertebral Disc Degeneration: New Insights from Bioinformatic Strategies

“…Moreover, to further explore the biological functions of OSIDDRGs, we performed the function enrichment analysis and identified several crucial KEGG pathways which might be involved in IDD. In fact, several of these identified signaling pathways have been verified in IDD, including TNF signaling pathway [45], estrogen signaling pathway [7], MAPK signaling pathway [46], HIF-1 signaling pathway [47], Toll-like receptor signaling pathway [48], and glutathione metabolism [49]. However, how the OSIDDRGs participate in IDD via these signaling pathways has not been fully understood and needs the further investigation.…”

Scutellarin Protects Against Mitochondrial Reactive Oxygen Species-Dependent NLRP3 Inflammasome Activation to Attenuate Intervertebral Disc Degeneration

“…Previous studies have shown that elevated expression of inflammatory cytokines is a critical factor leading to IVDD ( Liu K. et al, 2021 ). To investigate the role of scutellarin in the progression of the inflammatory response during IVDD, primary human nucleus pulposus cells (HNPCs) were isolated and then cultured with TNF-α in the presence or absence of scutellarin for 24 h to detect the mRNA level and 48 h to detect the protein level of inflammatory biomarkers.…”

Hypoxia-Inducible Factor-1α Protects Against Intervertebral Disc Degeneration Through Antagonizing Mitochondrial Oxidative Stress

“…TNF-α has been shown to be associated with a variety of pathological IDD processes such as inflammatory cascade, ROS production, apoptosis, ECM degradation, pyroptosis and proliferation. These indicate their critical role in the development of IVDD [25,26]. Additionally, it can also induce an inflammatory response in the nucleus pulposus, leading to an increase of iNOS and COX2 and acceleration of intervertebral disc destruction [27].…”