Blood vessels are primary targets for 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin in pre-cardiac edema formation in larval zebrafish. (September 2020) - Nijoukubo, Daisuke
Abstract: 2, 3, 7, 8-Tetrachlorodibenzo- p -dioxin (TCDD) has adverse effects on the development and function of the heart in zebrafish eleutheroembryos (embryos and larvae). We previously reported that TCDD reduced blood flow in the mesencephalic vein of zebrafish eleutheroembryos long before inducing pericardial edema. In the present study, we compared early edema (pre-cardiac edema), reduction of deduced cardiac output and reduction of blood flow in the dorsal aorta and cardinal vein caused by TCDD. In the same group of eleutheroembryos, TCDD (1.0 ppb) caused pre-cardiac edema and circulation failure at the cardinal vein in the central trunk region with the similar time courses from 42 to 54 h post fertilization (hpf), while the same concentration of TCDD did not significantly affect aortic circulation in the central trunk region or cardiac output. The dependence of pre-cardiac edema on TCDD concentration (0–2.0 ppb) at 55 hpf correlated well with the dependence of blood flow through the cardinal vein on TCDD concentration. Several treatments that markedly inhibited TCDD-induced pre-cardiac edema such as knockdown of aryl hydrocarbon receptor nuclear translocator-1 (ARNT1) and treatment with ascorbic acid, an antioxidant, did not significantly prevent the reduction of cardiac output at 55 hpf caused by 2.0 ppb TCDD. TCDD caused hemorrhage and extravasation of Evans blue that was intravascularly injected with bovine serum albumin, suggesting an increase in endothelium permeability to serum protein induced by TCDD. The results suggest that the blood vessels are primary targets of TCDD in edema formation in larval zebrafish. Highlights: Mechanistic process of TCDD-induced edema is unclear. Low concentration of TCDD evoked edema without an effect on cardiac function. Concentration-dependence of TCDD on edema was correlated with vein blood flow. TCDD increased permeability of vessel wall to serum albumin. TCDD caused edema and hemorrhage that were inhibited by common treatments.