The role of toll-like receptors in the protective effect of melatonin against doxorubicin-induced pancreatic beta cell toxicity

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dc.authoridKAYA, Salih Tunc/0000-0002-4133-407X
dc.authoridkocahan, sayad/0000-0002-3161-1280
dc.authoridSevgiler, Yusuf/0000-0002-4373-2389
dc.authoridGUR, FATIH MEHMET/0000-0001-7748-3272
dc.contributor.authorTaskin, Eylem
dc.contributor.authorGuven, Celal
dc.contributor.authorKaya, Salih Tunc
dc.contributor.authorSahin, Leyla
dc.contributor.authorKocahan, Sayad
dc.contributor.authorDegirmencioglu, Arife Zuhal
dc.contributor.authorGur, Fatih Mehmet
dc.date.accessioned2024-11-07T13:34:55Z
dc.date.available2024-11-07T13:34:55Z
dc.date.issued2019
dc.departmentNiğde Ömer Halisdemir Üniversitesi
dc.description.abstractAims: Doxorubicin, an anticancer drug, has a toxic effect on many tissues such as heart, pancreas, liver, kidney, and testis. The aim of current study is to investigate whether melatonin would be protective in doxorubicin-induced beta (beta) cell toxicity via HMGB1/TLR2/TLR4/MAPK/NF-kappa B signaling pathway. Main methods: Human pancreatic beta cell (1.1B4) was used in the present study. Four experimental groups were created as control, melatonin (10 mu M), doxorubicin (2 mu M) and the combination of melatonin with doxorubicin. Following 24-h treatment, Mitogen-activated protein kinase (MAPKs), Toll like receptors (TLRs) including TLR2 and TLR4, pro-and anti-apoptotic protein expression levels were determined by western blotting. Total antioxidant (TAS), oxidant status (TOS) and oxidative stress index (OSI) of the cells as well as superoxide dismutase (SOD) levels were determined. Active caspase-8 activity was measured and TUNEL staining was performed to study apoptotic pathways. Mitochondrial membrane potential (MMP), some protein expressions and F-actin distribution were analyzed. Key findings: Doxorubicin caused to depolarize MMP, resulting in enhancing apoptosis by activation of caspase-8 via MAPKs/NF-kappa B pathway via elevation of TOS and decreasing TAS. Also, doxorubicin destroyed F-actin distribution and elevated TLR2 and some apoptotic proteins, including Bax. However, co-treatment of melatonin with doxorubicin could reverse depolarization of MMP and inhibition of apoptosis through MAPK/NF-kappa B signaling by decreasing TOS and increasing TAS. The co-treatment reversed the alternations of TLR2, TLR4, MAPKs and apoptotic protein expressions induced by doxorubicin. Significance: Melatonin could be a good candidate against pancreatic beta cell toxicity-induced by doxorubicin through TLR2/TLR4/MAPK/NF-kappa B pathways.
dc.description.sponsorshipNigde Omer Halisdemir University Scientific Research Projects Coordination Unit, Nigde/Turkey [SSB2017/01-BAGEP]
dc.description.sponsorshipThis work was supported by the Nigde Omer Halisdemir University Scientific Research Projects Coordination Unit, Nigde/Turkey [grant number SSB2017/01-BAGEP]
dc.identifier.doi10.1016/j.lfs.2019.116704
dc.identifier.issn0024-3205
dc.identifier.issn1879-0631
dc.identifier.pmid31369761
dc.identifier.scopus2-s2.0-85069926528
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.lfs.2019.116704
dc.identifier.urihttps://hdl.handle.net/11480/16246
dc.identifier.volume233
dc.identifier.wosWOS:000484035300029
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherPergamon-Elsevier Science Ltd
dc.relation.ispartofLife Sciences
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_20241106
dc.subjectDoxorubicin
dc.subjectMelatonin
dc.subjectBeta cell
dc.subjectToll like receptors
dc.subjectOxidative stress
dc.subjectProtein kinases
dc.titleThe role of toll-like receptors in the protective effect of melatonin against doxorubicin-induced pancreatic beta cell toxicity
dc.typeArticle

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