Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
Cardiovascular diseases are major cause of mortality in many countries. Increase of permeability in vascular endothelium is a prelude of chronic cardiovascular diseases including atherosclerosis. Epidemiological studies indicate significant relationship between dioxins exposure and chronic cardiovascular disease. While pathophysiological role of aryl hydrocarbon receptor (AHR) has been unveiled, mechanisms of actions by dioxins are not fully clarified. Zebrafish is a small tropical cyprinoid fish with many advantage such as an exclusion from ethical problem in early larva especially in EU. We reported that type 2 aryl hydrocarbon receptor (AHR2) other than AHR1a and b mostly mediates toxicological responses such as cardiovascular failure caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and involvement of COX2s-thromboxane pathway in circulation failure and edema. While many studies focused on heart as a target of TCDD, we obtained evidence that endothelium is a primary target of TCDD. Although oxidative stress has been frequently reported as one of major players in TCDD-induced cardiovascular diseases, which mechanism is unclear. Some antioxidants inhibit TCDD-induced circulation failure and edema in zebrafish. Conversely, oxidative stress inducers augment edema induced by both TCDD and thromboxane receptor agonist, suggesting the site of action is thromboxane receptor or the following signaling pathway. The mechanism of TCDD-induced circulation failure will be discussed.
