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. 2021 Jun 29;10:e57245. doi: 10.7554/eLife.57245

Figure 10. Additive survival effects of paired lead compounds in zebrafish RP model.

Figure 10.

Box plots of rod cell survival effects of seven lead compounds tested alone and in pairs in rho:YFP-NTR zebrafish larvae (assays performed as per confirmation tests, see Figure 2A). To test for enhanced survival, all compounds were tested at maximal effective dosages. Eleven pairs promoted a statistically significant increase in survival relative to both individual compound controls (++), while five pairs performed better than a single compound control (+). Survival effects (normalized YFP %), 95% confidence intervals, p-values, and sample sizes (N) for each condition are shown in the table below. For comparison, the survival effect of each pair (Effect %) and the summed effect of the respective individual compound controls (Sum %) are provided. Additive effects were defined as any pair that promoted survival at equal to or greater than the sum of the corresponding individual compound effects ±10%. By this criterion, 10 pairs produced additive effects (bolded values). Three pairs produced effects greater than 25% above the summed effect and were considered potentially synergistic (asterisks). A minimum of three experimental repeats were performed for each condition and data pooled across replicates (Figure 10—source data 1). No statistical differences in larval survival were observed for lead compounds or compound pairs relative to their respective +Mtz controls, except for DHA (73%), WAR+DHA (73%), CIC+DHA (89%), ZPT+DHA (91%), ZPT+COR (90%) and CAL+COR (79%; Fisher’s exact test, p<0.05). Two pairs, DHA+CAL and DHA+COR resulted in total lethality and are not plotted. See Supplementary file 1c for survival effects (normalized YFP %), 95% confidence intervals and p-values relative to ablated controls (+Mtz) and to respective individual compound controls, and sample sizes (N) for all conditions. Lead compound abbreviations: WAR, Warfarin; CLO, Cloxyquin; CPO, Ciclopirox olamine; MIC, Miconazole; ZPT, Zinc pyrithione; DHA, Dihydroartemisinin; CHL, Chloroxine; CAL, Calcimycin; SUL, Sulindac; ART, Artemisinin; COR, Cortexolone; POS, positive control. Other abbreviations: CI, confidence interval; Mtz, Metronidazole.

Figure 10—source data 1. Paired compound tests.