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Cerebrospinal inflammatory response following scorpion envenomation: role of histamine H1 and H3 receptors

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

The results showed that the histamine H1 receptor is more involved in the induced central nervous system inflammatory response during scorpion envenomation.

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Abbreviations

Aah:

Androctonus australis hector

cAMP:

Cyclic adenosine monophosphate

H2O2 :

Hydrogen peroxide

IL:

Interleukin

MAPK:

Mitogen-activated protein kinases

MDA:

Malondialdehyde

NF-kB:

Nuclear factor-kappa B

NMRI:

Naval Medical Research Institute

NO:

Nitric oxide

PRRs:

Pattern-recognition receptors

TLR:

Toll-like receptor

TNF-α:

Tumor necrosis factor-α

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Authors and Affiliations

  1. USTHB, Laboratory of Cellular and Molecular Biology, Faculty of Biological Sciences, BP 32, El-Alia, Bab Ezzouar, Algiers, Algeria

    Amal Megdad-Lamraoui, Sonia Adi-Bessalem & Fatima Laraba-Djebari

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  1. Amal Megdad-Lamraoui
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  2. Sonia Adi-Bessalem
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  3. Fatima Laraba-Djebari
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Correspondence to Fatima Laraba-Djebari.

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Megdad-Lamraoui, A., Adi-Bessalem, S. & Laraba-Djebari, F. Cerebrospinal inflammatory response following scorpion envenomation: role of histamine H1 and H3 receptors. Inflammopharmacol 27, 589–601 (2019). https://doi.org/10.1007/s10787-018-00553-6

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