Article Figures & Data
Figures
- Figure 1.
Effects of the proteasome inhibitors PS-341 (A), MG132 (B), and lactacystin (C) on the radiation sensitivity of zebrafish embryos. Embryos were irradiated at 24 hpf and survival was scored every day up to 7 dpf. Results shown represent mean ± SD of triplicate experiments. *, statistically significant difference in survival at 6 to 7 dpf.
- Figure 2.
Protection against and mitigation of lethal effects of radiation by direct NF-κB inhibitors. Differential survival of zebrafish embryos pretreated with EP (A and C) or CDDO-TFEA (B and D) and exposed to either 20 or 40 Gy as indicated. E, radiation protection of zebrafish embryos exposed to 20 Gy and treated for 1 h prior to irradiation with different IKK inhibitors. F, increased survival of irradiated (20 Gy) zebrafish embryos treated with EP (1mmol/L) or CDDO-TFEA (1 μmol/L) 2 h post radiation at 24 hpf. Survival was scored at 7 dpf. All results shown represent mean ± SD of triplicate experiments. *, statistically significant differences in survival at 7 dpf between drug-treated and vehicle-treated groups.
- Figure 3.
Reduction of organism-wide apoptosis by EP and CDDO-TFEA treatment preradiation and postradiation. Acridine orange (AO) staining of whole embryos was done 6 h postradiation at 30 hpf. A, representative examples of control or irradiated fish revealing strong AO staining in the central nervous system and along the body axis induced by radiation (20 Gy). Regions selected for quantitative evaluation are boxed. B, reduced AO staining in CDDO-TFEA- and EP-treated embryos exposed to ionizing radiation. C, PS-341 or MG132 treatment does not significantly affect AO staining of embryos exposed to ionizing radiation.
- Figure 4.
Effects of EP and CDDO-TFEA on radiation-induced kidney damage as determined by dextran clearance. A, Representative images of dextran retention in irradiated embryos and effects of EP and CDDO-TFEA on this phenomenon. B, quantitative representation of dextran retention in embryos treated with either EP or CDDO-TFEA as indicated; results are expressed relative to vehicle-treated, nonirradiated controls. *, statistically significant differences between the experimental groups indicated by brackets.
- Figure 5.
EP and CDDO-TFEA alleviate radiation-induced malformations of the body axis. A, representative micrographs showing dorsal curvature (“curly-up”; cup) in irradiated (20 Gy) embryos at 72 hpf relative to control nonirradiated fish embryos. B, quantification of curly-up incidence in CDDO-TFEA- and EP-treated fish relative to vehicle-treated controls. *, statistically significant differences between the experimental groups indicated by brackets.
- Figure 6.
Effects of EP and CDDO-TFEA on radiation-induced alterations of the gastrointestinal system. A, improved PLA2 activity and gastrointestinal lumen formation in irradiated zebrafish treated with either EP or CDDO-TFEA. Dequenched fluorescence reflects endogenous PLA2 activity and transport of cleavage products through the lumen of the developing gastrointestinal system. B, quantitative evaluation of gastrointestinal lumen formation as determined by fluorescent dye content at 6 dpf. C, representative histologic sections of hindgut proximal to the cloaca at 6 dpf [5 d post (12 Gy)].
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Volume 8, Issue 9
