Administration of N-Acetylcysteine to Regress the Fibrogenic and Proinflammatory Effects of Oxidative Stress in Hypertrophic Ligamentum Flavum Cells

Abstract

Ligamentum flavum hypertrophy (LFH) is a major cause of lumbar spinal stenosis (LSS). In hypertrophic ligamentum flavum (LF) cells, oxidative stress activates intracellular signaling and induces the expression of inflammatory and fibrotic markers. This study explored whether healthy and hypertrophic LF cells respond differently to oxidative stress, via examining the levels of phosphorylated p38 (p-p38), inducible nitric oxide synthase (iNOS), and α-smooth muscle actin (α-SMA). Furthermore, the efficacy of N-acetylcysteine (NAC), an antioxidant, in reversing the fibrogenic and proinflammatory effects of oxidative stress in hypertrophic LF cells was investigated by assessing the expression levels of p-p38, p-p65, iNOS, TGF-β, α-SMA, vimentin, and collagen I under H2O2 treatment with or without NAC. Under oxidative stress, p-p38 increased significantly in both hypertrophic and healthy LF cells, and iNOS was elevated in only the hypertrophic LF cells. This revealed that oxidative stress negatively affected both hypertrophic and healthy LF cells, with the hypertrophic LF cells exhibiting more active inflammation than did the healthy cells. After H2O2 treatment, p-p38, p-p65, iNOS, TGF-β, vimentin, and collagen I increased significantly, and NAC administration reversed the effects of oxidative stress. These results can form the basis of a novel therapeutic treatment for LFH using antioxidants.

Exploring lncRNA Expression Patterns in Patients With Hypertrophied Ligamentum Flavum

“…The GO analysis revealed that these lncRNAs were mainly associated with metabolic processes, organelles, nuclear lumen, cytoplasm, protein binding, nucleic acid binding, and transcription factor activity. These results are consistent with those of previous studies that have implicated alterations in cellular metabolism [ 32 ], organelle function [ 33 ], and transcriptional regulation [ 34 , 35 ] in LFH pathogenesis. Furthermore, the KEGG pathway analysis showed several signaling pathways that might be associated with the differentially expressed lncRNAs, including the hippo signaling pathway, nucleotide excision repair, SNARE interactions in vesicular transport, and the NF-kappa B signaling pathway.…”

Nonsurgical therapy for lumbar spinal stenosis caused by ligamentum flavum hypertrophy: A review

“…[84] NAC is a precursor of glutathione, which is converted to glutathione in vivo [85] and subsequently inhibits the expression of many oxidative and fibrotic markers and inflammatory mediators in hypertrophic LF cells, attenuating the adverse effects of oxidative stress on LF. [86,87] Moreover, inflammation of the cauda equina and nerve roots is often accompanied by LSS, [88] and NAC attenuates the longterm inflammatory response of the nerves and the toxic effects induced by free radicals, suggesting that NAC may be protective against the inflammatory nerve roots and cauda equina in LSS. [89,90] Similar to NAC, harpagophytum procumbens (HP) also plays an antioxidant role via the Nrf2/NQO-1 signaling pathway.…”