Gisele Graça Leite Dos Santos1, Anna Lethícia Lima Oliveira1, Dourivaldo Silva Santos2, Renan Fernandes do Espírito Santo1, Daniela Nascimento Silva3, Paulo José Lima Juiz4, Milena Botelho Pereira Soares5, Cristiane Flora Villarreal6. 1. Gonçalo Moniz Institute, Oswaldo Cruz Foundation-FIOCRUZ, 40296-710 Salvador, BA, Brazil. 2. College of Pharmacy, Federal University of Bahia, 40170-115 Salvador, BA, Brazil. 3. SENAI Institute of Innovation in Advanced Health Systems (ISI SAS), University Center SENAI/CIMATEC, 41650-010 Salvador, Bahia, Brazil. 4. Federal University of Recôncavo of Bahia, 44042-280 Feira de Santana, BA, Brazil. 5. Gonçalo Moniz Institute, Oswaldo Cruz Foundation-FIOCRUZ, 40296-710 Salvador, BA, Brazil; SENAI Institute of Innovation in Advanced Health Systems (ISI SAS), University Center SENAI/CIMATEC, 41650-010 Salvador, Bahia, Brazil. 6. Gonçalo Moniz Institute, Oswaldo Cruz Foundation-FIOCRUZ, 40296-710 Salvador, BA, Brazil; College of Pharmacy, Federal University of Bahia, 40170-115 Salvador, BA, Brazil. Electronic address: cfv@ufba.br.
Abstract
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 × 106), 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-1β and TNF-α spinal levels did not differ between mice with or without sensory neuropathy. MSC increased the levels of anti-inflammatory cytokines, IL-10 and TGF-β, 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.
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 × 106), 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-1β and TNF-α spinal levels did not differ between mice with or without sensory neuropathy. MSC increased the levels of anti-inflammatory cytokines, IL-10 and TGF-β, in the spinal cord of neuropathicmice, 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.
Authors: Anna Lethicia L Oliveira; Gisele G L Santos; Renan F Espirito-Santo; Gessica Sabrina A Silva; Afrânio F Evangelista; Daniela N Silva; Milena B P Soares; Cristiane Flora Villarreal Journal: Stem Cells Int Date: 2021-01-06 Impact factor: 5.443