Involvement of the Endothelin Receptor Type A in the Cardiovascular Inflammatory Response Following Scorpion Envenomation.

Amina Sifi,Sonia Adi-Bessalem,Fatima Laraba-Djebari

doi:10.3390/toxins12060389

Abstract

Elevated levels of endothelin-1 (ET-1) were recorded in sera of scorpion sting patients. However, no studies focused on the mechanism of ET-1 involvement in the pathogenesis of scorpion envenomation, particularly in the cardiovascular system which is seriously affected in severe cases of scorpion stings. Inflammation induced by Androctonus australis hector (Aah) scorpion venom in the heart together with the aorta was studied in mice pretreated with a specific endothelin A receptor (ETA-R) inhibitor. ETA-R inhibition resulted in the attenuation of the high amounts of cytokine (tumor necrosis factor alpha (TNF-α) and interleukin-17 (IL-17)) recorded in the sera of envenomed mice. The recovery of the oxidative stress marker balance and matrix metalloproteinase (MMP) expression were also observed, concomitantly with the reduction of tissular neutrophil infiltration. Additionally, the cardiac and the aortic tissue alterations, and the metabolic enzymes (creatine kinase (CK) and muscle–brain isoform creatine kinase (CK-MB)) overspread into sera were significantly attenuated. Obtained results suggest the implication of endothelin throughout its ETA receptors in the inflammatory response observed in the cardiovascular components during scorpion envenomation. Further knowledge is needed to better understand the implication of the endothelin axis and to improve the therapeutic management of severe scorpion sting cases.

Highlights

Scorpion sting envenomation is, in the majority of severe cases, the cause of heart failure and hemodynamic changes that can lead to pulmonary edema [1,2,3,4,5,6,7,8,9]
Results show a significant increase in both TNF-α absence of the selective endothelin A receptor (ETA-R) antagonist, BQ123
The inhibition of the ETA receptor prior to the injection of the venom led to a significant decrease in TNF-α (p < 0.01) and IL-17 (p < 0.05) levels compared to the envenomed animals (Figure decrease in TNF-α (p < 0.01) and IL-17 (p < 0.05) levels compared to the envenomed animals (Figure 1)

Summary

Introduction

In the majority of severe cases, the cause of heart failure and hemodynamic changes that can lead to pulmonary edema [1,2,3,4,5,6,7,8,9]. The inflammatory process and the overproduction of free radicals are frequently triggered by scorpion venom and promote. Toxins 2020, 12, x FOR PEER REVIEW inflammatory process and the overproduction of free radicals are frequently triggered by scorpion venom and promote cardiac injury [7,16,19,20]. 12, 389 recognition receptors (PRRs) of the innate immune system (Toll-like receptors, TLR2 and TLR4), activate nuclear factor kappa-B (NF-κB) transcription factor, and increase pro-inflammatory cardiac injury. Oxygen free radicalsvenom (ROS),components which thenbind leads to pattern cardiac recognition oxidative stress and (PRRs) of the innate immune system (Toll-like receptors, TLR2 and TLR4), activate nuclear factor cardiotoxicity [7,21,22,23,24,25,26]. Oxygen free radicalsvenom (ROS),components which thenbind leads to pattern cardiac recognition oxidative stress and (PRRs) of the innate immune system (Toll-like receptors, TLR2 and TLR4), activate nuclear factor cardiotoxicity [7,21,22,23,24,25,26]. kappa-B (NF-κB)

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Discussion

Conclusion