Abstract
Animal slaughtering causes the cessation of oxygen delivery and that of nutrients such as cystine, glucose and others to muscle cells. In muscle cells, the changes in oxygen level and pH cause mitochondria, the endoplasmic reticulum, xanthine oxidase and uncoupled NOS to increase the level of O(2)(•-), affecting the generation of H(2)O(2) and the release of iron ions from ferritin. The activation of enzymes that remove and dislocate fatty acids from the membrane affects the sensitivity of muscle cells to peroxidation and ferroptosis. Increasing PUFAs in membrane phospholipids, by feeding animals a diet high in w-3 fatty acids, is a driving factor that increases lipid peroxidation and possible muscle ferroptosis. The activation of lipoxygenases by ROS to Fe(3+)-lipoxygenase increases hydroperoxide levels in cells. The labile iron pool generated by a "redox cycle" catalyzes phospholipid hydroperoxides to generate lipid electrophiles, proximate executioners of ferroptosis. Ferroptosis in food muscle cells is protected by high concentrations of vitamin E and selenium. In fresh muscle cells, glutathione peroxidase (GSH-PX) and other endogenous antioxidant enzymes are active and prevent lipid peroxidation; however, muscle heating eliminates enzymatic activities, making cells prone to high non-enzymatic lipid peroxidation. In muscle cells, coupled myoglobin and vitamin E act as a hydroperoxidase, preventing the generation of lipid electrophiles. Free iron ion chelators or effectors such as deferoxamine, EDTA, or ceruloplasmin are strong inhibitors of muscle cell lipid peroxidation, proving that muscle ferroptosis is mostly dependent on and catalyzed by the labile iron redox cycle.