The crotoxin: SBA-15 complex down-regulates the Incidence and Intensity of experimental autoimmune encephalomyelitis through peripheral and central actions
Sant´Anna, Morena Brazil Martins ; Giardini, Aline Carolina ; Ribeiro, Marcio A. C.; Lopes, Flávia Souza Ribeiro ; Teixeira, Nathália Bernardes ; Kimura, Louise Faggionato ; Búfalo, Michelle Cristiane ; Ribeiro, Orlando Garcia ; Borrego, Andrea ; Cabrera, Wafa Hanna Koury ; Ferreira, Julio C. B.; Zambelli, Vanessa Olzon ; Sant'Anna, Osvaldo Augusto Brazil Esteves ; Picolo, Gisele
Crotoxin (CTX), the main neurotoxin from Crotalus durissus terrificus snake venom, has anti-inflammatory, immunomodulatory and antinociceptive activities. However, the CTX-induced toxicity may compromise its use. Under this scenario, the use of nanoparticle such as nanostructured mesoporous silica (SBA-15) as a carrier might become a feasible approach to improve CTX safety. Here, we determined the benefits of SBA-15 on CTX-related neuroinflammatory and immunomodulatory properties during experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis that replicates several histopathological and immunological features observed in humans. We showed that a single administration of CTX:SBA-15 (54 μg/kg) was more effective in reducing pain and ameliorated the clinical score (motor impairment) in EAE animals compared to the CTX-treated EAE group; therefore, improving the disease outcome. Of interest, CTX:SBA-15, but not unconjugated CTX, prevented EAE-induced atrophy and loss of muscle function. Further supporting an immune mechanism, CTX:SBA-15 treatment reduced both recruitment and proliferation of peripheral Th17 cells as well as diminished IL-17 expression and glial cells activation in the spinal cord in EAE animals when compared with CTX-treated EAE group. Finally, CTX:SBA-15, but not unconjugated CTX, prevented the EAE-induced cell infiltration in the CNS. These results provide evidence that SBA-15 maximizes the immunomodulatory and anti-inflammatory effects of CTX in an EAE model; therefore, suggesting that SBA-15 has the potential to improve CTX effectiveness in the treatment of MS.
crotoxin; SBA-15; mesoporous silica; experimental autoimmune encephalomyelitis (EAE); IL-17; neuroinflammation; motor impairment
Sant´Anna MBM, Giardini AC, Ribeiro MA.C., Lopes FSR, Teixeira NB, Kimura LF, et al. The crotoxin: SBA-15 complex down-regulates the Incidence and Intensity of experimental autoimmune encephalomyelitis through peripheral and central actions. Front. Immunol.. 2020 Oct;11:591563. doi:10.3389/fimmu.2020.591563.
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