Involvement of Ferroptosis in Diabetes-Induced Liver Pathology
2022
Аутори:
Stančić, AnaVeličković, Ksenija
Markelić, Milica
Grigorov, Ilijana
Saksida, Tamara
Savić, Nevena
Vučetić, Milica
Martinović, Vesna
Ivanović, Anđelija
Otašević, Vesna
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
Cell death plays an important role in diabetes-induced liver dysfunction. Ferroptosis is a
newly defined regulated cell death caused by iron-dependent lipid peroxidation. Our previous studies
have shown that high glucose and streptozotocin (STZ) cause -cell death through ferroptosis and
that ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, improves -cell viability, islet morphology, and
function. This study was aimed to examine in vivo the involvement of ferroptosis in diabetes-related
pathological changes in the liver. For this purpose, male C57BL/6 mice, in which diabetes was induced
with STZ (40 mg/kg/5 consecutive days), were treated with Fer-1 (1 mg/kg, from day 1–21 day). It
was found that in diabetic mice Fer-1 improved serum levels of ALT and triglycerides and decreased
liver fibrosis, hepatocytes size, and binucleation. This improvement was due to the Fer-1-induced
attenuation of ferroptotic events in the liver of diabetic mice, such as accumulation of pro-oxidative
parameters (iron, lipofuscin, 4-HNE), decrease in expression level/activity of antioxidative defenserelated
molecules (GPX4, Nrf2, xCT, GSH, GCL, HO-1, SOD), and HMGB1 translocation from nucleus
into cytosol. We concluded that ferroptosis contributes to diabetes-related pathological changes in
the liver and that the targeting of ferroptosis represents a promising approach in the management of
diabetes-induced liver injury.
Кључне речи:
feroptosis; liver; diabetes; oxidative stress; lipid peroxidation; Nrf2Извор:
International Journal of Molecular Sciences, 2022, 23, 16, 9309-Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
- Science Fund of the Republic of Serbia (Serbian Science and Diaspora Collaboration Program: Knowledge Exchange Vouchers, #Grant No. 6525651
DOI: 10.3390/ijms23169309
ISSN: 1422-0067
PubMed: 36012572