Key result
Pretreatment with the ETA receptor antagonist BQ123 significantly attenuated venom-induced cardiovascular inflammation, oxidative stress, and tissue alterations in mice.
Why the study?
Elevated endothelin-1 occurs after scorpion stings, but its mechanistic role in cardiovascular pathogenesis during envenomation had not been studied.
Does ETA-R inhibition attenuate the cardiovascular inflammatory response in mice following scorpion envenomation?
Does ETA-R inhibition attenuate the cardiovascular inflammatory response in mice following scorpion envenomation?
Inhibition of the endothelin A receptor attenuates cardiovascular inflammation and tissue damage in a mouse model of scorpion envenomation.
ETA receptor blockade may mitigate scorpion venom cardiotoxicity; hypothesis-generating in mice and leaves open human translation.
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.
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Sifi et al. (2020) studied Scorpion envenomation (n=24). BQ123 (ETA receptor antagonist) vs. Scorpion venom alone and saline control was evaluated on Cardiovascular inflammatory response (cytokines, oxidative stress, tissue damage). Pretreatment with the ETA receptor antagonist BQ123 significantly attenuated venom-induced cardiovascular inflammation, oxidative stress, and tissue alterations in mice.
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