Laquinimod attenuates oxidative stress-induced mitochondrial injury and alleviates intervertebral disc degeneration by inhibiting the NF-κB signaling pathway

Background: Low back pain (LBP) caused by intervertebral disc degeneration (IVDD) is a significant global health concern. It is necessary to investigate the underlying pathological mechanisms leading to IVDD and develop precise treatment strategies for this condition. Considering the well-established anti-inflammatory properties and ability to reduce oxidative stress in various diseases, for the first time we aim to explore the potential of Laquinimod in alleviating IVDD.

Methods: We used hydrogen peroxide (H₂O₂) to simulate the oxidative stress microenvironment in IVDD, and Laquinimod for intervention purposes. Western blot analysis, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence assay were used to measure the expression levels of inflammatory cytokines, catabolic enzymes, and markers of extracellular matrix (ECM) synthesis in nucleus pulposus (NP) cells. In addition, dichlorofluorescin-diacetate (DCFH-DA) and JC-1 fluorescent probes, flow cytometry analysis, and qRT-PCR were used to measure mitochondrial function and Apoptosis in NP cells under conditions of oxidative stress. An acupuncture-induced rat model of IVDD was established to further evaluate the efficacy of Laquinimod in alleviating IVDD in vivo.

Results: Our findings showed that Laquinimod significantly reduced the oxidative stress-induced inflammatory response in NP cells, downregulated the expression of catabolic enzymes, and markedly enhanced ECM degradation by inhibiting the NF-κB signaling pathway. The administration of Laquinimod concurrently improved the mitochondrial functional state and reduced Apoptosis in NP cells. Additionally, in vivo experiments in rats showed that Laquinimod significantly alleviated acupuncture-induced IVDD.

Conclusions: Collectively, the findings of this study provide new insights into the therapeutic potential of Laquinimod as a treatment for oxidative stress-induced IVDD.

Apoptosis; Intervertebral disc degeneration; Laquinimod; NF-κB; Oxidative stress.