Endogenous humoral determinants of vascular endothelial dysfunction as triggers of acute poisoning complications. Issue 1 (24th March 2022)

• Record Type: Journal Article
• Authors: Ivnitsky, Jury Ju.; Schäfer, Timur V.; Rejniuk, Vladimir L.; Golovko, Alexandr I.
• Is Part Of: Journal of applied toxicology. Volume 43:Issue 1(2023)
• Page Start: 47
• Page End: 65
• Publication Date: 2022-03-24
• Subjects: acute poisoning complication -- endogenous humoral factors -- endotheliotoxicants -- individual risk assessment -- vascular endothelial dysfunction; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.4312
• Languages: English
• ISSNs: 0260-437X

Abstract

Abstract: The vascular endothelium is not only the semipermeable membrane that separates tissue from blood but also an organ that regulates inflammation, vascular tone, blood clotting, angiogenesis and synthesis of connective tissue proteins. It is susceptible to the direct cytotoxic action of numerous xenobiotics and to the acute hypoxia that accompanies acute poisoning. This damage is superimposed on the preformed state of the vascular endothelium, which, in turn, depends on many humoral factors. The probability that an exogenous toxicant will cause life‐threatening dysfunction of the vascular endothelium, thereby complicating the course of acute poisoning, increases with an increase in the content of endogenous substances in the blood that disrupt endothelial function. These include ammonia, bacterial endotoxin, indoxyl sulfate, para ‐cresyl sulfate, trimethylamine N ‐oxide, asymmetric dimethylarginine, glucose, homocysteine, low‐density and very‐low‐density lipoproteins, free fatty acids and products of intravascular haemolysis. Some other endogenous substances (albumin, haptoglobin, haemopexin, biliverdin, bilirubin, tetrahydrobiopterin) or food‐derived compounds (ascorbic acid, rutin, omega‐3 polyunsaturated fatty acids, etc.) reduce the risk of lethal vascular endothelial dysfunction. The individual variability of the content of these substances in the blood contributes to the stochasticity of the complications of acute poisoning and is a promising target for the risk reduction measures. Another feasible option may be the repositioning of drugs that affect the function of the vascular endothelium while being currently used for other indications. Abstract : The vascular endothelium is damaged by the direct cytotoxic action of numerous xenobiotic chemicals and (or) acute hypoxia. This damage is superimposed on the initial state of vascular endothelium, which, in turn, depends on many endogenous humoral factors. Vascular endothelium dysfunction increases the acute poisoning complications risk. Approach to the prevention of acute poisoning complications is considered.