Rattlesnake venom components in the control of experimental autoimmune encephalomyelitis: Immunomodulatory properties potentiated by silica SBA-15

Background: Multiple sclerosis (MS) is an inflammatory, autoimmune and demyelinating disease of the CNS, which causes sensory and motor impairments. MS has no cure, and the available therapies are only able to delay the progression of the disease. Animal venoms and toxins have being considered a rich source for the search of therapeutic drug candidates, since these components in general can exhibit selectivity and affinity for a wide variety of targets in mammalian systems. In this meaning, studies using compounds isolated from crotalic venoms, particularly crotoxin and crotalphine have indicated their analgesic, anti-inflammatory, immunomodulatory and anti-tumoral properties. Then, the effect of both components was investigated in the experimental autoimmune encephalomyelitis (EAE) model, an animal model of multiple sclerosis. Methods: EAE was induced by immunization of female C57BL/6 mice with MOG35–55 peptide (200μg) and M. tuberculosis (400μg) in incomplete Freund’s adjuvant, followed by pertussis toxin injection (300ng, on days 0 and 2).Pain threshold was determined using an electronic pressure-meter test. Clinical signs were assessed according to scores from 0 to 5.Results showed that, CTX, in a single dose, was effective in controlling pain symptoms but does not interfere with clinical signs. However, in 5 consecutive doses, CTX modulates both mechanical hypernociception and clinical signs (motor impairment) in animals with EAE. Furthermore, treatment with CTX reduced production/release of central pro-inflammatory mediators. These effects were potentiated when CTX was adsorbed in silica SBA-15, an inert nanoestruturated mesoporous silica. In relation to crotalphine (CRO), our results showed that CRO caused partial reversion of EAE-induced hyperalgesia and decreased the severity of the clinical signs of EAE when compared to saline-treated animals.CRO reduced the immunoreactivity of the Egr-1, microglia/macrophages and astrocytes markers induced by EAE. In addition, it decreased CD11b expression and increased IL-6 in spinal cord. Discussion/Conclusion: These Results reinforce the immunomodulatory effect of crotoxin and crotalphine, confirming this effect in a model of neurodegenerative disease, where both compounds could act attenuating the neuroinflammation induced by EAE. These results confer to both CTX and CRO characteristics to be used as promising candidates for the control of multiple sclerosis.
Experimental Autoimmune Encephalomyelitis;  Crotoxin;  Crotalphine;  Neuroinflammation;  SBA-15 silica

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Sant´Anna MBM, Giardini AC, Lopes FSR, Kimura LF, Chacur M., Pagano R.L., et al. Rattlesnake venom components in the control of experimental autoimmune encephalomyelitis: Immunomodulatory properties potentiated by silica SBA-15. Toxicon. 2020 July;182(supl.1):S22. doi:10.1016/j.toxicon.2020.04.054.
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