Institute of Nutrition, State University of Rio de Janeiro, Rio de Janeiroe, Brazil,
Institute of Nutrition, State University of Rio de Janeiro, Rio de Janeiroe, Brazil.
Cell Physiol Biochem. 2023 Apr 15;57(S1):24-41. doi: 10.33594/000000620.
Ferroptosis is a regulated non-apoptotic cell death process triggered by excessive iron-induced lipid peroxidation. Excess intracellular iron promotes lipid peroxidation by increasing reactive oxygen species formation through the Fenton reaction. Thus, iron and polyunsaturated fatty acid intake may trigger ferroptosis under certain conditions. The aims of this review were to compile and examine evidence in the literature for the effects of iron and polyunsaturated fatty acid supplementation on ferroptosis. Omega-6 polyunsaturated fatty acids have relatively greater susceptibility to lipid peroxidation and could, therefore, participate in ferroptosis. By contrast, omega-3 polyunsaturated fatty acids promote intracellular antioxidants synthesis and reduce the formation of hydroperoxides that induce ferroptosis. As intestinal iron absorption is regulated by iron nutritional status, individuals with normal functioning of the hepcidin-ferroportin axis are at low risk of developing iron overload in response to ingestion of iron-rich foods. Therefore, iron supplementation is potentially toxic mainly for the intestinal epithelium and the microbiota. In animal models, iron-rich diets increased oxidative damage, lowered the glutathione concentration within hepatocytes, and downregulated desaturases that synthesize long-chain polyunsaturated fatty acids. These adverse effects of iron supplementation were prevented by omega-3 fatty acid co-supplementation. The impact of food and supplement intake on ferroptosis has seldom been investigated. Scientific evidence still does not allow us to know for sure whether iron and PUFA supplementation are capable of inducing ferroptosis. As the mechanisms that control ferroptosis can determine whether cells proliferate or die, future studies should directly investigate the effects of nutrient supplementation and food intake on the ferroptosis process in different types of cells and tissues.
铁死亡是一种由过量铁诱导的脂质过氧化引发的受调控的非凋亡性细胞死亡过程。过量的细胞内铁通过芬顿反应增加活性氧的形成来促进脂质过氧化。因此，在某些条件下，铁和多不饱和脂肪酸的摄入可能会引发铁死亡。本综述的目的是编译和检查文献中关于铁和多不饱和脂肪酸补充对铁死亡影响的证据。ω-6 多不饱和脂肪酸对脂质过氧化的敏感性相对较高，因此可能参与铁死亡。相比之下，ω-3 多不饱和脂肪酸促进细胞内抗氧化剂的合成，并减少诱导铁死亡的过氧化物的形成。由于肠道铁吸收受铁营养状况的调节，铁调素-亚铁转运蛋白轴功能正常的个体在摄入富含铁的食物时，发生铁过载的风险较低。因此，铁补充剂主要对肠上皮细胞和微生物群有毒性。在动物模型中，富含铁的饮食增加了氧化损伤，降低了肝细胞内谷胱甘肽的浓度，并下调了合成长链多不饱和脂肪酸的去饱和酶。ω-3 脂肪酸的共同补充预防了铁补充的这些不利影响。食物和补充剂摄入对铁死亡的影响很少被研究。科学证据还不能确定铁和多不饱和脂肪酸补充剂是否能够诱导铁死亡。由于控制铁死亡的机制可以决定细胞是增殖还是死亡，因此未来的研究应该直接研究营养补充剂和食物摄入对不同类型细胞和组织中铁死亡过程的影响。
