Protective effects of Sulphorhane against injury of endocrine pancreas in diabetic mice include antiferroptotic action
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2024
Аутори:
Markelić, MilicaStančić, Ana
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Veličković, Ksenija
Martinović, Vesna
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Gudelj, Anđelija
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Otašević, Vesna
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Grigorov, Ilijana
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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 sulphur-containing compound with various beneficial biological
effects that is found in cruciferous vegetables. Among others, these effects include the activation
of Nrf2, a transcription factor that plays an important role in the prevention of ferroptosis, a
cell death characterized by the accumulation of labile iron, glutathione (GSH) depletion and lipid
peroxidation. Recently, we have demonstrated the antiferroptotic hepatoprotective effect of SFN in
diabetic mice. Since ferroptosis has also been confirmed by us and others as one of the causes of
β-cell destruction in diabetes, we aimed to investigate the potential of SFN treatment in
preventing/eliminating injury of pancreatic islets during diabetes development in vivo. For this
purpose, male C57BL/6 mice were divided into four groups (n=8): Control (Crtl), SFN-treated (SFN,
2.5 mg/kg), diabetic (DM, treated with 40 mg/kg streptozotocin from day 1-5) and diabetic
SFN-treated (DM+SFN) group. All animals received an intraperitoneal injection of SFN or vehicle for
42 days and were sacrificed on day 43. Pancreata were isolated and prepared for histologic analysis
and determination of GSH content. Glycemia was measured once a week during the experiment.
Consistent with the improved glycemia, we observed histologic evidence of improvement in the
endocrine pancreas of the DM+SFN animals: pancreatic GSH content was restored, average islet size
and insulin immunopositivity returned to control values, and there was less insulitis than in the
DM group. Lipid peroxidation, which was greatly increased in the DM islets as shown by 4-HNE
immunopositivity, also decreased in the DM+SFN animals, while Nrf2 increased. As a sign of improved
islet regeneration, PDX-1 immunoexpression strongly increased in this group. To investigate whether
SFN as a natural H2S donor affects the endogenous production of this gasotransmitter in islet
cells, immunoexpression of cystathionine-β- synthase (CBS) and cystathionine gamma-lyase (CSE) was
also analyzed. The results showed that SFN increased CBS expression in islets under diabetogenic
insults. In summary, we have shown that SFN prevents diabetogenic islet damage by activating
antiferroptotic signaling pathways. Moreover, our results indicate the importance of the H2S/CBS
signaling pathway in protecting islet cells from DM
insult, indicating this pathway as a potential antidiabetic target.
Кључне речи:
sulforaphane; diabetes; feroptosis; endocrine pancreasФинансирање / 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. 41. (Genetics & Applications; Special Issue).