An In Vivo Zebrafish Model for Interrogating ROS-Mediated Pancreatic β-Cell Injury, Response, and Prevention

Figure 5

Proposed mechanism of metronidazole-nitroreductase-mediated cell ablation. In the aerobic setting of NTR-expressing eukaryotic cells, we propose that MTZ is reduced to a nitroradical anion by electron transfer from NADH, in a type 2-like mechanism. This radical may be cytotoxic and directly induces DNA damage and apoptosis. Alternately, this radical may regenerate back to metronidazole by electron transfer to O₂, concurrently forming superoxide anion and ROS derivatives. This, in turn, drives increased cellular-oxidative stress and triggering of regulated cell death.