Browsing by Subject "ferroptosis"
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Item A macrocyclic molecule with multiple antioxidative activities protects the lens from oxidative damage(Frontiers Media S.A., 2022-11-18) Zhang, Jinmin; Yu, Yu; Mekhail, Magy A.; Wu, Hongli; Green, Kayla N.Growing evidence links oxidative stress to the development of a cataract and other diseases of the eye. Treatments for lens-derived diseases are still elusive outside of the standard surgical interventions, which still carry risks today. Therefore, a potential drug molecule (OH)Py(2)N(2) was explored for the ability to target multiple components of oxidative stress in the lens to prevent cataract formation. Several pathways were identified. Here we show that the (OH)Py(2)N(2) molecule activates innate catalytic mechanisms in primary lens epithelial cells to prevent damage induced by oxidative stress. This protection was linked to the upregulation of Nuclear factor erythroid-2-related factor 2 and downstream antioxidant enzyme for glutathione-dependent glutaredoxins, based on Western Blot methods. The anti-ferroptotic potential was established by showing that (OH)Py(2)N(2) increases levels of glutathione peroxidase, decreases lipid peroxidation, and readily binds iron (II) and (III). The bioenergetics pathway, which has been shown to be negatively impacted in many diseases involving oxidative stress, was also enhanced as evidence by increased levels of Adenosine triphosphate product when the lens epithelial cells were co-incubated with (OH)Py(2)N(2). Lastly, (OH)Py(2)N(2) was also found to prevent oxidative stress-induced lens opacity in an ex vivo organ culture model. Overall, these results show that there are multiple pathways that the (OH)Py(2)N(2) has the ability to impact to promote natural mechanisms within cells to protect against chronic oxidative stress in the eye.Item Folic acid-induced animal model of kidney disease(John Wiley & Sons Australia, Ltd, 2021-11-24) Yan, Liang-JunThe kidneys are a vital organ that is vulnerable to both acute kidney injury (AKI) and chronic kidney disease (CKD) which can be caused by numerous risk factors such as ischemia, sepsis, drug toxicity and drug overdose, exposure to heavy metals, and diabetes. In spite of the advances in our understanding of the pathogenesis of AKI and CKD as well AKI transition to CKD, there is still no available therapeutics that can be used to combat kidney disease effectively, highlighting an urgent need to further study the pathological mechanisms underlying AKI, CKD, and AKI progression to CKD. In this regard, animal models of kidney disease are indispensable. This article reviews a widely used animal model of kidney disease, which is induced by folic acid (FA). While a low dose of FA is nutritionally beneficial, a high dose of FA is very toxic to the kidneys. Following a brief description of the procedure for disease induction by FA, major mechanisms of FA-induced kidney injury are then reviewed, including oxidative stress, mitochondrial abnormalities such as impaired bioenergetics and mitophagy, ferroptosis, pyroptosis, and increased expression of fibroblast growth factor 23 (FGF23). Finally, application of this FA-induced kidney disease model as a platform for testing the efficacy of a variety of therapeutic approaches is also discussed. Given that this animal model is simple to create and is reproducible, it should remain useful for both studying the pathological mechanisms of kidney disease and identifying therapeutic targets to fight kidney disease.