4.7 Article

Mesenchymal stem cells reduce the oxaliplatin-induced sensory neuropathy through the reestablishment of redox homeostasis in the spinal cord

期刊

LIFE SCIENCES
卷 265, 期 -, 页码 -

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PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2020.118755

关键词

Neuropathic pain; Chemotherapy; Mesenchymal cells; Oxidative stress; Cytokines

资金

  1. Fundacao de Amparoa Pesquisa do Estado da Bahia -FAPESB [Brazil] [RED0010/2012]

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The study found that MSC can completely reverse the mechanical allodynia and thermal hyperalgesia induced by OXL-induced sensory neuropathy. MSC increased the gene expression of antioxidant factors SOD and Nrf-2, elevated the levels of anti-inflammatory cytokines IL-10 and TGF-beta in the spinal cord of neuropathic mice, and decreased nitrite and MDA levels, possibly inducing the reversal of OXL-induced sensory neuropathy by activating anti-inflammatory and antioxidant pathways.
Aims: The present study was designed to investigate whether the antinociceptive effect of bone marrow-derived mesenchymal stem/stromal cells (MSC) during oxaliplatin (OXL)-induced sensory neuropathy is related to antioxidant properties. Main methods: Male mice C57BL/6 were submitted to repeated intravenous administration of OXL (1 mg/kg, 9 administrations). After the establishment of sensory neuropathy, mice were treated with a single intravenous administration of MSC (1 x 10(6)), vehicle or gabapentin. Paw mechanical and thermal nociceptive thresholds were evaluated through von Frey filaments and cold plate test, respectively. Motor performance was evaluated in the rota-rod test. Gene expression profile, cytokine levels, and oxidative stress markers in the spinal cord were evaluated by real-time PCR, ELISA and biochemical assays, respectively. Key findings: OXL-treated mice presented behavioral signs of sensory neuropathy, such as mechanical allodynia and thermal hyperalgesia, which were completely reverted by a single administration of MSC. Repeated oral treatment with gabapentin (70 mg/kg) induced only transient antinociception. The IL-1 beta and TNF-alpha spinal levels did not differ between mice with or without sensory neumpathy. MSC increased the levels of anti-inflammatory cytokines, IL-10 and TGF-beta, in the spinal cord of neuropathic mice, in addition to increasing the gene expression of antioxidant factors SOD and Nrf-2. Additionally, nitrite and MDA spinal levels were reduced by the MSC treatment. Significance: MSC induce reversion of sensory neuropathy induced by OXL possibly by activation of anti-inflammatory and antioxidant pathways, leading to reestablishment of redox homeostasis in the spinal cord.

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