1. The Crotoxin:SBA-15 Complex Down-Regulates the Incidence and Intensity of Experimental Autoimmune Encephalomyelitis Through Peripheral and Central Actions.
- Author
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Sant'Anna MB, Giardini AC, Ribeiro MAC, Lopes FSR, Teixeira NB, Kimura LF, Bufalo MC, Ribeiro OG, Borrego A, Cabrera WHK, Ferreira JCB, Zambelli VO, Sant'Anna OA, and Picolo G
- Subjects
- Animals, Biomarkers, Biopsy, Crotoxin adverse effects, Crotoxin chemistry, Cytokines metabolism, Disease Management, Disease Models, Animal, Disease Susceptibility, Encephalomyelitis, Autoimmune, Experimental diagnosis, Female, Mice, Muscle, Skeletal immunology, Muscle, Skeletal metabolism, Muscle, Skeletal pathology, Severity of Illness Index, Spinal Cord immunology, Spinal Cord metabolism, Spinal Cord pathology, Symptom Assessment, Crotoxin administration & dosage, Encephalomyelitis, Autoimmune, Experimental etiology, Encephalomyelitis, Autoimmune, Experimental metabolism, Immunomodulation drug effects, Silicon Dioxide, Theranostic Nanomedicine
- Abstract
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., (Copyright © 2020 Sant'Anna, Giardini, Ribeiro, Lopes, Teixeira, Kimura, Bufalo, Ribeiro, Borrego, Cabrera, Ferreira, Zambelli, Sant'Anna and Picolo.)
- Published
- 2020
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