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Nuclear Factor Κb Inhibitors Alleviate And The Proteasome Inhibitor Ps-341 Exacerbates Radiation Toxicity In Zebrafish Embryos, Borbala Daroczi, Gabor Kari, Qing Ren, Adam Dicker Md, Phd, Ulrich Rodeck

Bodine Journal

Inflammatory changes are a major component of the normal tissue response to ionizing radiation, and increased nuclear factor κB (NF-κB) activity is an important mediator of inflammatory responses. Here, we used zebrafish embryos to assess the capacity of two different classes of pharmacologic agents known to target NF-κB to modify radiation toxicity in the vertebrate organism. These were proteasome inhibitors, including lactacystin, MG132, and PS-341 (Bortezomib/VELCADE), and direct inhibitors of NF-κB activity, including ethyl pyruvate (EP) and the synthetic triterpenoid CDDO-TFEA (RTA401), among others. The proteasome inhibitors either did not significantly affect radiation sensitivity of zebrafish embryos (MG132, lactacystin) or …