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Involvement of Toll-like Receptor 4 in Neutrophil-Mediated Inflammation, Oxidative Stress and Tissue Damage Induced by Scorpion Venom

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Abstract

Systemic inflammatory response and generation of oxidative stress are known to contribute to scorpion venom-induced tissue damage. TLR receptors might represent a link between oxidative stress and inflammation; we therefore investigated whether or not TLR4 is involved in venom-induced immunopathology. The obtained results showed that pharmacological targeting of TLR4 with the selective inhibitor TAK-242 (Resatorvid) prevents the inflammatory response induced by subcutaneous administration of Androctonus australis hector (Aah) venom, as revealed by a significant decrease of neutrophil cell count in peripheral blood associated with significant decline of neutrophil degranulation and sequestration to the lung, liver, and kidney tissues. Moreover, TAK-242 administration inhibited nitrite levels increase in serum, malondialdehyde (MDA), and protein carbonyl tissue contents concomitantly with a significant increase of catalase activity and reduced glutathione (GSH) level in tissue homogenates. Furthermore, venom-induced increases in serum levels of organ dysfunction markers (lactate deshydrogenase, aminotransferase ALT and AST, creatinine and urea) were also significantly suppressed by pre-treatment with TLR4 inhibitor, concordantly with a remarkable improvement in the histological features in lung and liver tissues. The results of the present study indicate the potential role of TLR4 in venom-induced immunopathology and show the in vivo requirement of TLR4 signaling in mediating venom-induced tissue damage.

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  1. USTHB, Faculty of Biological Sciences, Laboratory of Cellular and Molecular BiologyB, BP32 El-Alia, Bab Ezzouar, 16111, Algiers, Algeria

    Dalila Khemili, Fatima Laraba-Djebari & Djelila Hammoudi-Triki

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  1. Dalila Khemili
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Correspondence to Fatima Laraba-Djebari.

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Khemili, D., Laraba-Djebari, F. & Hammoudi-Triki, D. Involvement of Toll-like Receptor 4 in Neutrophil-Mediated Inflammation, Oxidative Stress and Tissue Damage Induced by Scorpion Venom. Inflammation 43, 155–167 (2020). https://doi.org/10.1007/s10753-019-01105-y

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