Cerebrospinal inflammatory response following scorpion envenomation: role of histamine H1 and H3 receptors
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The mechanism of the inflammatory process induced by scorpion venom in the cerebrospinal tissues has not yet been completely elucidated. Therefore, we aimed to investigate the role of histamine through its H1 and H3 receptors in this process.
Histamine H1 and H3 receptor antagonists, Hydroxyzine (10 mg/kg) and Betaserc (20 mg/kg), respectively, were administered by intraperitoneal route to mice 1 h before subcutaneous envenomation with a subletal dose (0.5 mg/kg) of Androctonus australis hector venom. Cerebrospinal inflammation response was assessed 24 h after envenomation by evaluating the vascular permeability changes, inflammatory cell infiltration, oxidative/nitrosative stress marker levels (hydrogen peroxide, nitric oxide, malondialdehyde, glutathione and catalase) and by histological examination of cerebrospinal tissue.
Envenomed mice displayed an installation of an inflammatory response marked by increased vascular permeability (76% and 68% in brain and spinal cord, respectively, in comparison to controls), inflammatory cell infiltration, increased pro-oxidant levels and decreased anti-oxidant markers (p < 0.05 to p < 0.001). Scorpion venom also induced structural changes in brain and spinal cord tissues. Hydroxyzine seemed to be more efficient than Betaserc in the prevention of the induced cerebrospinal inflammation response, as evidenced by the decreased vascular permeability, inflammatory cell infiltration, pro-oxidant levels, increased anti-oxidant defense (p < 0.05 to p < 0.001) and a reduction of the anatomo-pathological alterations.
The results showed that the histamine H1 receptor is more involved in the induced central nervous system inflammatory response during scorpion envenomation.
KeywordsScorpion venom Inflammatory response Cerebrospinal tissues Histamine H1-receptor Histamine H3-receptor
Androctonus australis hector
Cyclic adenosine monophosphate
Mitogen-activated protein kinases
Nuclear factor-kappa B
Naval Medical Research Institute
Tumor necrosis factor-α
- Banks WA, Lynch JL, Price TO (2009) Cytokines and the blood–brain barrier. In: Siegel A, Zalcman S (eds) The neuroimmunological basis of behavior and mental disorders, vol 2009. Springer Science+ Business Media, pp 3–17Google Scholar
- Karin M, Delhase M (2000) The IκB kinase (IKK) and NF-κB: key elements of proinflammatory signalling. In: Seminars in immunology, vol 12. Elsevier, Amsterdam, pp 85–98Google Scholar
- Krawisz J, Sharon P, Stenson W (1984) Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity: assessment of inflammation in rat and hamster models. Gastroenterology 87:1344–1350Google Scholar
- Lu C, Diehl SA, Noubade R, Ledoux J, Nelson MT, Spach K, Zachary JF, Blankenhorn EP, Teuscher C (2010) Endothelial histamine H1 receptor signaling reduces blood–brain barrier permeability and susceptibility to autoimmune encephalomyelitis. Proc Natl Acad Sci USA 107:18967–18972CrossRefGoogle Scholar
- Snyder S, Snowman A (1987) Receptor effects of cetirizine. Ann Allergy 59:4–8Google Scholar
- Zoccal KF, Bitencourt CD, Paula-Silva FWG, Sorgi CA, Bordon KDF, Arantes EC, Faccioli LH (2014) TLR2, TLR4 and CD14 recognize venom-associated molecular patterns from Tityus serrulatus to induce macrophage-derived inflammatory mediators. Plos ONE 9.2:e88174Google Scholar