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

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.