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Fig. 6
Synergy between NAC and PGE2 limits toxicity and extends the therapeutic window in adult zebrafish after APAP. Adult zebrafish were exposed to APAP and NAC, dmPGE2, or a combination either concomitantly or with 18 h del. (A) GSH (nmoles/whole liver) was improved by combined exposure to NAC and dmPGE2. *ANOVA, n = 3–4, P < 0.01. (B) Relative caspase 3/7 levels were elevated after APAP and improved with immediate NAC and/or dmPGE2; delayed combinatorial therapy was still beneficial. *ANOVA, n = 4–5, P < 0.001. (C) Serum ALT levels (n = 10–20 fish/treatment at 24 hpe) show that combined NAC and dmPGE2 prevented hepatocyte damage by APAP, even after delay. (D) Combined NAC and dmPGE2 treatment led to improved adult zebrafish survival (n = 9–10/treatment) at 48 hpe. (E) Effect of delayed treatment on zebrafish liver histology at 24 hpe; sinusoidal hemorrhage and necrosis in APAP-treated adults could not be reversed with NAC or dmPGE2 alone but only with combined treatment.