Paraquat augments 2,3,7,8-tetrachlorodibenzo-p-dioxin-evoked pre-cardiac edema in an antioxidant-sensitive manner. Eleutheroembryos were treated with 0.1 ppb 2,3,7,8-tetrachlorodibenzo-p-dioxin (0.1 TCDD or TCDD) or a vehicle (0.1% DMSO) (Control) beginning at 24 hpf. Paraquat (Para) (an oxidative stress inducer) (100 µg/ml), 20 µM N-acetylcysteine (NAC) (A), and 10 mM ascorbic acid (Asco) (B) were also included in some cases. Chemicals were newly changed at 48 hpf. At 55 hpf, the area of the pre-cardiac cavity was determined as an index of TCDD-induced edema (pre-cardiac edema, dashed circles in insets). Results are expressed as percentage of the control (means ± SEM, n=19–21). Values with different letters are significantly different (P<0.05).

Nuclear factor erythroid 2-related factor 2 (Nrf2) activators inhibit 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced pre-cardiac edema. Eleutheroembryos were treated with 1.0 ppb 2,3,7,8-tetrachlorodibenzo-p-dioxin (1.0 TCDD or TCDD) or a vehicle beginning at 24 hpf. Sulforaphane (40 µM) (A) and 2.5 µM auranofin (B) were also included, beginning at 24 hpf and 33 hpf, respectively. Chemicals were newly changed at 48 hpf and pre-cardiac cavity was evaluated at 55 hpf. Results are expressed as percentage of the control (means ± SEM). n=18–21 (A), n=20 (B). Values with different letters are significantly different (P<0.05).

No effects of paraquat on expression of cyclooxygenase 2 and cytochrome P450 1A expression. Paraquat (Para) (100 µg/ml) and 0.1 ppb 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.1 TCDD or TCDD) were applied from 24 hpf and larvae were harvested at 55 hpf for RT-qPCR of cyclooxygenase 2b (COX2b) (A) and cytochrome P450 1A (CYP1A) (B). Chemicals were newly changed at 48 hpf. Results are expressed as arbitrary unit (means ± SEM). n=5 (A, B). Values with different letters are significantly different (P<0.05).

Paraquat augments pre-cardiac edema caused by thromboxane receptor activation in an antioxidant-sensitive manner. Paraquat (Para) (100 µg/ml), U46619 (7.5 µM) (7.5 U) and N-acetylcystein (NAC) (20 µM) (A), ascorbic acid (Asco) (10 mM) (B) were applied from 48 hpf and pre-cardiac cavity was evaluated at 55 hpf. Results are expressed as percentage of the control (means ± SEM). n=20 (A), n=19–22 (B). Values with different letters are significantly different (P<0.05).

Potentiation of thromboxane receptor agonist-induced pre-cardiac edema by an oxidative stress inducer was sensitive to a thromboxane receptor blocker and a prostacyclin receptor agonist. Paraquat (Para) (100 µg/ml), ICI-192,605 (ICI) (24 µM), beraprost (Bera) (10 µM,) and U46619 (0.5 µM) were applied from 48 hpf and pre-cardiac cavity was evaluated at 55 hpf. Results are expressed as percentage of the control (means ± SEM). n=20. Values with different letters are significantly different (P<0.05).

A nuclear factor erythroid 2-related factor 2 inducer inhibits oxidative stress-induced augmentation of pre-cardiac edema by thromboxane receptor activation. U46619 (7.5 µM) (7.5 U), paraquat (Para) (100 µg/ml) and sulforaphane (40 µM) (SF) were applied from 48 hpf and pre-cardiac cavity was evaluated at 55 hpf. Results are expressed as percentage of the control (means ± SEM, n=19–21). Values with different letters are significantly different (P<0.05).