Please use this identifier to cite or link to this item: https://biore.bio.bg.ac.rs/handle/123456789/6363
Title: Antiferroptotic approach for the treatment of diabetes-induced liver pathology: the effects of ethyl pyruvate
Authors: Stančić Ana
Otašević Vesna
Markelić, Milica 
Veličković, Ksenija 
Gudelj Anđelija
Savić Nevena
Martinović Vesna
Grigorov Ilijana
Keywords: ethyl pyruvate;diabetes;liver;ferroptosis
Issue Date: 23-Apr-2023
Rank: M34
Publisher: EMBO
metadata.dc.identifier.artno: 040
Start page: 92
Conference: EMBO Workshop "Ferroptosis: When metabolism meets cell death"
Abstract: 
We showed recently that ferroptosis contributes to liver pathological changes in diabetes. So,
targeting of ferroptosis-related pathways could be novel approach for treatment of diabetesrelated
liver diseases. Ethyl pyruvate (EP) showed antidiabetic action due to anti-oxidative, -
inflammatory and -apoptotic properties. We aimed to examine its potential antiferroptotic action
in diabetes-related liver pathology.
Male Wistar rats were divided into four groups: control; diabetic (STZ, 65 mg/kg); diabetic pretreated
with EP (80 mg/kg/day, starting one week before STZ and continuing following 4
weeks) and diabetic treated with EP, starting with STZ and lasted 4 weeks.
Both modes of EP treatment induced attenuation of ferroptotic events in the liver of diabetic
rats: accumulation of lipid peroxides (4-HNE), disturbances in iron metabolism (decreased
FTH and increased TFR expression), decrease in expression level/activity of ferroptosisrelated
antioxidative-defense molecules (GPX4, GCL, GSS, Nrf2, HO-1), and activation of
ferroptosis-related pro-inflammatory events (HMGB1 nucleus-to-cytosol and NF-kB cytosol-tonucleus
translocation). Those changes reflected on the improvement of diabetes-related
morphological alterations such as liver fibrosis and binucleation.
Overall, EP interferes with ferroptosis signaling pathways and exerts antiferroptotic activity in
the liver in diabetic state. This highlighting the significance of ferroptosis targeting in diabetesrelated
liver diseases and novel mechanisms/targets of EP beneficial actions.
URI: https://biore.bio.bg.ac.rs/handle/123456789/6363
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