Anti-inflammatory Activity of Caspian Cobra (Naja naja oxiana) Snake Venom on the Serum Level of Interleukin-27 and Histopathological Changes in Myelin Oligodendrocyte Glycoprotein-experimental Autoimmune Encephalomyelitisinduced Mice

Abstract

Multiple sclerosis (MS) is considered a chronic disease of the central nervous system, with a strong neurodegenerative component. The exact mechanism of MS is not clear. However, the therapeutic strategies for controlling MS are based on immune modulation and inflammation control. Regarding this, the present study was conducted to investigate the influence of snake venom on the suppression of the immune system after the induction of experimental autoimmune encephalomyelitis (EAE) in mice. For this purpose, C57BL/6 female mice, divided into three groups, were selected to be induced by EAE. Groups 2 and 3 received flank injection with the emulsion of myelin oligodendrocyte glycoprotein (MOG 35-55), as well as complete Freund adjuvant, followed by the administration of pertussis toxin. Furthermore, the treatment group, as an immune-modulator, received cobra venom (CV) after EAE induction. The mice were then evaluated daily based on clinical symptoms, weight changes (within 26 days), histopathological analysis, and serum levels of interleukin 27 (IL-27) for neurological motor deficits. The clinical signs of MOG-EAE in C57BL/6 mice began 9-14 days post-immunization. Histopathological results also revealed that CV-treated EAE mice, compared to the untreated EAE group, witnessed a significant reduction in the intensity of inflammatory cells in parenchymal sections. Furthermore, the increase of IL-27 levels was significant in the CV-treated group (P=0.001), compared with those in the EAE and control groups. Based on results obtained in the present study, it may be concluded that Naja naja oxiana snake venom is a potential immunomodulatory agent that can be effective in the treatment of MS.

Keywords: Cobra venom; EAE; Interleukin-27; MOG 35-55; Multiple sclerosis.

Figure 1

Weight changes in EAE/MS and EAE/CV (A), clinical score changes in EAE /MS and EAE/CV (B) (C57BL/6 mice were subjected to EAE; then, the CV group was treated with cobra snake venom at two doses. Weight variation (a) and clinical score (b) were daily evaluated. Data are presented by mean ±SEM.) EAE: experimental autoimmune encephalomyelitis, MS: multiple sclerosis, CV: cobra ven

Figure 2

Immunohistochemical examination of the CNS inflammatory cell infiltration in the brain parenchyma in C57BL/6 mice (Animals were submitted to EAE and then treated with cobra venom); (a) healthy control mice, (b) positive control group with EAE, and (c) EAE-induced mice treated with venom CNS: central nervous system, EAE: experimental autoimmune encephalomyelitis

Figure 3

Variation in the serum levels of IL-27 in the control, EAE, and CV/EAE groups (The level of IL-27 in different groups, compared to those in the control group (*=P<0.05 and **=P<0.01]. The level of IL-27 in CV-EAE group, compared to that in the EAE group (***=P<0.001]) IL-27: interleukin-27, EAE: experimental autoimmune encephalomyelitis, CV: cobra venom