Anti-ferroptotic action of sulforaphane in skeletal muscle of diabetic mice
2024
Аутори:
Stančić, AnaMarkelić, Milica
Savić, Nevena
Veličković, Ksenija
Gudelj, Anđelija
Martinović, Vesna
Grigorov, Ilijana
Otašević, Vesna
Тип документа:
Конференцијски прилог (Објављена верзија)
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© 2024 by the Institute for Genetic Engineering and Biotechnology, University of Sarajevo
Метаподаци
Приказ свих података о документуАпстракт:
Sulforaphane (SFN) is a natural sulfur-rich compound found in cruciferous vegetables. SFN has been recognized as a powerful bioactive agent for reducing hyperglycemia and hyperlipidemia, improving insulin resistance, oxidative stress and inflammation in diabetic conditions. We aimed here to examine whether and how SFN affects diabetic-related skeletal muscle disorders associated with cell death signaling pathways. Precisely, the effect of SFN on ferroptosis, iron-dependent form of regulated cell death characterized by the accumulation of lipid peroxides, was examined. Male C57BL/6 mice were divided into four groups: control, diabetic (streptozotocin-induced; 40 mg/kg, from days 1 to 5), non- diabetic SFN-treated (SFN) and diabetic treated with SFN (DM + SFN). SFN was administrated i.p. in a dose of 2.5 mg/kg/day for 42 days. The results from histochemical analyses have shown the increased level of ferroptotic markers, seen as an accumulation of iron, as well 4-hydroxynonenal (4-HNE), an abundant end-product of lipid peroxidation, in skeletal muscle of diabetic animals. Along with this, there was decrease in antioxidant capacity, observed as lower immunohistochemical positivity for glutathione peroxidase 4 (GPX4), the main lipid peroxides-scavenging enzyme as well decrease in protein expression of cystine-glutamate antiporter system (xCT), the important determinant of intracellular synthesis of glutathione, GPX cofactor. Treatment of diabetic animals with SFN induced decreased accumulation of iron and 4-HNE and increased GPX4 immunopositivity and xCT protein level in skeletal muscle compared to the untreated diabetic animals. We can conclude that SFN has beneficial effects on the main core of ferroptosis signaling composed of xCT/GPX4/lipid peroxides axis and thus improves ferroptotic phenotype of skeletal muscle in diabetic conditions. This shed light on the new mechanism of SFN action over diabetes-related skeletal muscle dysfunction based on antiferroptotic action and nominates SFN as a promising phytoparmaceutical in the treatment of diabetes-related metabolic disorders
Кључне речи:
Sulforaphane; diabetes; skeletal muscle; ferroptosisФинансирање / 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)
У:
- Book of abstracts: 2nd European Symposium on Phytochemicals in Medicine and Food: 2-EuSPMF; 2024 Jun 3-6; Sarajevo, Bosnia and Herzegovina. Sarajevo: Institute for Genetic Engineering and Biotechnology, University of Sarajevo; 2024. p. 69. (Genetics & Applications; Special Issue).