Zhang Meng, Chen Xin, Zhang Yumei
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
Antioxidants (Basel). 2024 Dec 20;13(12):1571. doi: 10.3390/antiox13121571.
Ferroptosis is an iron-dependent form of cell death, which is characterized by the uncontrolled and overwhelming peroxidation of cell membrane lipids. Ferroptosis has been implicated in the progression of various pathologies, including steatotic liver, heart failure, neurodegenerative diseases, and diabetes. Targeted inhibition of ferroptosis provides a promising strategy to treat ferroptosis-related diseases. Multivitamins, including vitamins A, B, C, D, E, and K, have shown a good ability to inhibit ferroptosis. For example, vitamin A significantly upregulated the expression of several key ferroptotic gatekeepers genes through nuclear retinoic acid receptors and retinoic X receptors (RAR/RXR). Vitamin B6 could compensate for the impaired glutathione (GSH) levels and restore Glutathione peroxidase 4 (GPX4) expression in cells, ultimately inhibiting ferroptosis. Vitamin D could up-regulate the expression of several anti-ferroptosis proteins by activating vitamin D receptors. Vitamin E and hydroquinone vitamin K (VKH) can directly inhibit the propagation of lipid peroxidation, thereby inhibiting ferroptosis. In this review, we summarize the currently understood mechanisms by which vitamins inhibit ferroptosis to provide reference information for future research on the development of ferroptosis inhibitors.
铁死亡是一种铁依赖性的细胞死亡形式，其特征是细胞膜脂质的不受控制且过度的过氧化。铁死亡与多种病理学进展有关，包括脂肪性肝病、心力衰竭、神经退行性疾病和糖尿病。对铁死亡的靶向抑制为治疗与铁死亡相关的疾病提供了一种有前景的策略。多种维生素，包括维生素A、B、C、D、E和K，已显示出良好的抑制铁死亡的能力。例如，维生素A通过核视黄酸受体和视黄酸X受体（RAR/RXR）显著上调了几个关键铁死亡守门基因的表达。维生素B6可以补偿受损的谷胱甘肽（GSH）水平并恢复细胞中谷胱甘肽过氧化物酶4（GPX4）的表达，最终抑制铁死亡。维生素D可以通过激活维生素D受体上调几种抗铁死亡蛋白的表达。维生素E和对苯二酚维生素K（VKH）可以直接抑制脂质过氧化的传播，从而抑制铁死亡。在本综述中，我们总结了目前所了解的维生素抑制铁死亡的机制，以为未来铁死亡抑制剂开发的研究提供参考信息。
