Sulforaphane prevents diabetes-induced liver ferroptosis through activation of Nrf2 signaling axis
2023
Аутори:
Otašević, VesnaGrigorov, Ilijana
Savić, Nevena
Markelić, Milica
Veličković, Ksenija
Gudelj, Anđelija
Martinović, Vesna
Stančić, Ana
Остала ауторства
Conrad, MarcusJiang, Xuejun
Fedorova, Maria
Friedmann Angeli, José Pedro
Тип документа:
Конференцијски прилог (Објављена верзија)
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© 2023 by EMBO
Метаподаци
Приказ свих података о документуАпстракт:
Recently, we characterized the ferroptotic phenotype of the liver of diabetic mice and revealed the inactivation of Nrf2 as an integral part of diabetes-induced liver ferroptosis. We aim here to examine does sulforaphane, an Nrf2 activator and antioxidant, prevent diabetes-induced liver ferroptosis and the mechanisms involved.
For that purpose, male C57BL/6 mice were divided into three groups: control, diabetic (streptozotocin-treated, 40 mg/kg/5 consecutive days), diabetic+sulforaphane treated (2.5 mg/kg, from day 1-42).
Results showed that diabetes-induced inactivation of Nrf2 and decreased expression of its downstream antiferroptotic parameters crucial for antioxidative defense (HO-1, catalase, SOD), iron metabolism (ferroportin, ferritin), glutathione synthesis (xCT, GCLC, CTH, CBS) and recycling (GR) were reversed/increased by sulforaphane treatment. Antiferroptotic effect of sulforaphane in the diabetic liver was further evidenced through the increased level of glutathione, decreased accumulation of liable iron and lipid peroxides (4-HNE) and decreased tissue damage (fibrosis and infiltration). Finally, diabetes-induced increase in serum glucose, ALT, AST and triglyceride level was significantly reduced by sulforaphane.
These findings revealed for the first time that sulforaphane prevents in vivo diabetes-induced liver ferroptosis through activation of Nrf2 signaling axis. This suggests sulforaphane as a promising therapeutic tool for preventing ferroptosis at least in diabetes and diabetes-related pathologies.
Кључне речи:
diabetic mice; liver feroptosis; Nrf2 signaling; sulforaphaneФинансирање / пројекти:
- 6525651‚Program saradnje srpske nauke sa dijasporom: Vaučeri za razmenu znanja, Fond za nauku Republike Srbije
У:
- Conrad M, Jiang X, Fedorova M, Friedmann Angeli JP, editors. EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany. EMBO; 2023. p. 39.