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

Yu Chia Hsu, Hao Chun Chuang, Kun Ling Tsai, Ting Yuan Tu, Yan Jye Shyong, Cheng Hsiang Kuo, Yuan Fu Liu, Shu Shien Shih, Cheng Li Lin

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number1380353
JournalOxidative Medicine and Cellular Longevity
Volume2022
DOIs
Publication statusPublished - 2022

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Ageing
  • Cell Biology

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