Fig. 5

Nucleoside supplementation rescues defects in liver regeneration and survival that are observed in Nrf2KO zebrafish (A) Representative multiphoton images of BrdU incorporation (yellow) in hepatocytes (magenta) derived from WT zebrafish exposed to DMSO, APAP, APAP + N-acetyl cysteine (NAC), or APAP + nucleoside (NS) cocktail (deoxyadenosine [dA], deoxyguanosine [dG], deoxycytidine [dC], and thymidine [dT]). Scale bars, 50 ?M. (B) Quantification of BrdU incorporation into hepatocytes (% mCherry+/BrdU+ cells) in WT zebrafish during liver regeneration following exposure to DMSO, APAP, APAP + NAC, or APAP + NS. p value was calculated using an unpaired two-tailed Student's t test. Data are shown as median and interquartile range, n = 15. (C) Representative multiphoton images of BrdU incorporation (yellow) in hepatocytes (magenta) derived from Nrf2KO zebrafish exposed to DMSO, APAP, APAP + NAC, or APAP + NS. Scale bars, 50 ?M. (D) Quantification of BrdU incorporation into hepatocytes (% mCherry+/BrdU+ cells) in Nrf2KO zebrafish during liver regeneration following exposure to DMSO, APAP, APAP + NAC, or APAP + NS. p value was calculated using an unpaired two-tailed Student's t test. Data are shown as median and interquartile range, n = 15. (E) Survival of WT zebrafish following exposure to DMSO, APAP, APAP + NAC, or APAP + NS for 72 h from 4 dpf. p values were calculated using a Mantel-Cox test comparing the survival of APAP + NS to APAP alone. Data are shown as mean ± SEM, n = 80. (F) Survival of Nrf2KO zebrafish following exposure to DMSO, APAP, APAP + NAC, or APAP + NS for 72 h from 4 dpf. p values were calculated using a Mantel-Cox test comparing survival of APAP + NS to APAP alone. Data are shown as mean ± SEM, n = 80. (G) Summary illustrating the temporal regulation of metabolic reprogramming during liver regeneration.