Fig. S4
GSNOR inhibition is hepatoprotective and enhances survival in embryos exposed to APAP via activation of the Nrf2 pathway. (A) Effect of chemical modulators of NO signaling during APAP-induced liver injury in Tg(lfabp:GFP) embryos. Tg(lfabp:GFP) embryos were exposed to a sublethal dose of APAP (5 mM) from 48 to 96 hpf in the presence or absence of either Deta (10 μM) or L-NAME (10 μM). Representative fluorescent photomicrographs were taken at 10x magnification. (B) Survival in embryos exposed to a lethal dose of APAP (10 mM) from 48 to 96 hpf in the presence or absence of the alternate NO donors Deta (10 μM) or GSNO (5 μM). N=75; Fisher’s exact test, *p<0.001. (C and D) Effect of GSNORi (1 μM) and/or APAP (5 mM) exposure from 48-72 hpf on induction of the Nrf2 target genes, prdx1 and hmox1, as determined by in situ hybridization at 72 hpf. Translation blocking ATG morpholino against nrf2 was injected at a concentration of 50 μM. |