Triphenyl phosphate-induced pericardial edema in zebrafish embryos is dependent on the ionic strength of exposure media

Developmental toxicity of the emerging contaminant cyclophosphamide and the integrated biomarker response (IBRv2) in zebrafish

“…The yolk sac could serve as a reservoir of chemicals in the embryonic body. 62 It was reported that neoplastic drug toxicity could induce yolk sac oedema in zebrafish embryos. 63 Plasma membrane perturbations induced by drug toxicity could result in yolk sac oedema.…”

“…The yolk sac is metabolically active, and toxicant uptake takes place at its epithelium through active or passive transport. 62 Because of its lipophilic nature, CP could be actively absorbed in the yolk epithelium and coupled with yolk globules to cause alterations in the yolk sac. Drug toxicity could act on the yolk-protein precursor (vitellogenin regulation) and cause energy deficiency in larvae.…”

Triphenyl phosphate-induced pericardial edema in zebrafish embryos is reversible following depuration in clean water

“…D-Mannitol does not impact TPHP uptake in embryos, demonstrating that mitigation of TPHP-induced pericardial edema is not an artifact of decreased embryonic doses of TPHP in the presence of D-Mannitol ( Wiegand et al, 2023 ). TPHP-induced pericardial edema is also associated with increased epidermal ionocyte and epidermal fold formation on the yolk sac epithelium, phenotypes that are rescued by co-exposing embryos to D-Mannitol ( Wiegand et al, 2022 , 2023 ). Finally, TPHP-induced pericardial edema does not occur in exposure solutions of low ionic strength (e.g., reverse osmosis water), with edema formation only occurring in exposure solutions with higher ionic strength (e.g., conditioned water from a recirculating system) ( Wiegand et al, 2023 ).…”

“…Prior studies in our lab have found that triphenyl phosphate (TPHP) – a widely used organophosphate-based flame retardant – blocks cardiac looping during zebrafish development in a concentration-dependent manner, a phenotype that is dependent on pericardial edema formation ( Isales et al, 2015 ; McGee et al, 2013 ; Mitchell et al, 2018 ; Reddam et al, 2019 ; Yozzo et al, 2013 ). Moreover, D-Mannitol – an osmotic diuretic that increases the osmolarity of the surrounding solution ( Papich, 2016 ) – and fenretinide – a synthetic retinoid that may promote epithelial wound repair ( Szymanski et al, 2020 ´ ) – are both able to block TPHP-induced pericardial edema ( Mitchell et al, 2018 , 2019 ; Reddam et al, 2019 ; Wiegand et al, 2022 , 2023 ). D-Mannitol does not impact TPHP uptake in embryos, demonstrating that mitigation of TPHP-induced pericardial edema is not an artifact of decreased embryonic doses of TPHP in the presence of D-Mannitol ( Wiegand et al, 2023 ).…”

“…Moreover, D-Mannitol – an osmotic diuretic that increases the osmolarity of the surrounding solution ( Papich, 2016 ) – and fenretinide – a synthetic retinoid that may promote epithelial wound repair ( Szymanski et al, 2020 ´ ) – are both able to block TPHP-induced pericardial edema ( Mitchell et al, 2018 , 2019 ; Reddam et al, 2019 ; Wiegand et al, 2022 , 2023 ). D-Mannitol does not impact TPHP uptake in embryos, demonstrating that mitigation of TPHP-induced pericardial edema is not an artifact of decreased embryonic doses of TPHP in the presence of D-Mannitol ( Wiegand et al, 2023 ). TPHP-induced pericardial edema is also associated with increased epidermal ionocyte and epidermal fold formation on the yolk sac epithelium, phenotypes that are rescued by co-exposing embryos to D-Mannitol ( Wiegand et al, 2022 , 2023 ).…”