Novel Treatment of Neuroinflammation Against Low Back Pain by Soluble Fullerol Nanoparticles

作者：Liu Qihai; Jin Li; Mahon Brian H; Chordia Mahendra D; Shen Francis H; Li Xudong^*

来源：Spine, 2013, 38(17): 1443-1451.

DOI：10.1097/BRS.0b013e31828fc6b7

• low back pain
• intervertebral disc degeneration
• dorsal root ganglia
• neuroinflammation
• reactive oxygen species
• fullerol
• free radical scavenging
• TNF-alpha
• inflammatory cytokine
• antioxidative enzyme

Study Design. An in vitro study to investigate the anti-inflammatory effects of fullerol on mouse dorsal root ganglia (DRG) under tumor necrosis factor (TNF)-alpha induction.
Objective. To evaluate the potential of a free radical scavenger, fullerol nanoparticles, to prevent DRG tissue and neuron inflammatory responses under TNF-alpha induction in vitro.
Summary of Background Data. Low back pain is one of the most common reasons for clinician visits in Western societies. Symptomatic intervertebral disc degeneration is strongly implicated as a cause of low back pain, as it results in DRG inflammation. Increased production of reactive oxygen species (ROS) is associated with DRG inflammation.
Methods. With or without fullerol treatment, DRG tissue and DRG neurons isolated from wild-type C3H/HeNCrl (Charles River Laboratories, Wilmington, MA) mice were cultured under TNF-a induction. The amount of intracellular ROS was measured with H 2 DCFDA (Life Technologies Corporation, Grand Island, NY) fluorescence staining. Cellular apoptosis was detected via terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. The expression of inflammatory as well as antioxidative enzyme genes in neurons was analyzed by real-time polymerase chain reaction. In addition, inflammatory cytokine expression in DRG tissue was determined by immunofluorescence staining and enzyme-linked immunosorbent assay.
Results. Fluorescence staining results indicated that TNF-alpha markedly increased the production of intracellular ROS and the number of apoptotic cells. Under fullerol treatment, cellular apoptosis was reduced along with concomitant suppression of ROS. The expression of inflammatory cytokines interleukin 1 beta, interleukin 6, cyclooxygenase-2, and prostaglandin E2, was also inhibited by fullerol in a dose-dependent manner. Furthermore, fullerol-treated cells exhibited upregulation of antioxidative enzyme genes superoxide dismutase 2 and catalase.
Conclusion. The results obtained from this study clearly suggest that fullerol treatment suppresses the inflammatory responses of DRG and neurons, as well as cellular apoptosis by decreasing the level of ROS and potentially enhancing antioxidative enzyme gene expression. Therefore, fullerol has potential to serve as a novel therapeutic agent for low back pain treatment.

• 出版日期2013-8-1