Ferroptosis inhibitor ferrostatin-1 attenuates morphine tolerance development in male rats by inhibiting dorsal root ganglion neuronal ferroptosis

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dc.authoridJoha, Ziad/0000-0001-8520-3760
dc.authoridTaskiran, Ahmet Sevki/0000-0002-5810-8415
dc.authoridDirik, Hasan/0000-0002-2274-5690
dc.contributor.authorDirik, Hasan
dc.contributor.authorTaskiran, Ahmet Sevki
dc.contributor.authorJoha, Ziad
dc.date.accessioned2024-10-26T18:07:13Z
dc.date.available2024-10-26T18:07:13Z
dc.date.issued2024
dc.departmentSivas Cumhuriyet Üniversitesi
dc.description.abstractBackground: Ferrostatin-1 and liproxstatin-1, both ferroptosis inhibitors, protect cells. Liproxstatin-1 decreases morphine tolerance. Yet, ferrostatin-1's effect on morphine tolerance remains unexplored. This study aimed to evaluate the influence of ferrostatin-1 on the advancement of morphine tolerance and understand the underlying mechanisms in male rats. Methods: This experiment involved 36 adult male Wistar albino rats with an average weight ranging from 220 to 260 g. These rats were categorized into six groups: Control, single dose ferrostatin-1, single dose morphine, single dose ferrostatin-1 + morphine, morphine tolerance (twice daily for five days), and ferrostatin-1 + morphine tolerance (twice daily for five days). The antinociceptive action was evaluated using both the hot plate and tail-flick tests. After completing the analgesic tests, tissue samples were gathered from the dorsal root ganglia (DRG) for subsequent analysis. The levels of glutathione, glutathione peroxidase 4 (GPX4), and nuclear factor erythroid 2-related factor 2 (Nrf2), along with the measurements of total oxidant status (TOS) and total antioxidant status (TAS), were assessed in the tissues of the DRG. Results: After tolerance development, the administration of ferrostatin-1 resulted in a significant decrease in morphine tolerance (P < 0.001). Additionally, ferrostatin-1 treatment led to elevated levels of glutathione, GPX4, Nrf2, and TOS (P < 0.001), while simultaneously causing a decrease in TAS levels (P < 0.001). Conclusions: The study found that ferrostatin-1 can reduce morphine tolerance by suppressing ferroptosis and reducing oxidative stress in DRG neurons, suggesting it as a potential therapy for preventing morphine tolerance.
dc.identifier.doi10.3344/kjp.24042
dc.identifier.endpage246
dc.identifier.issn2005-9159
dc.identifier.issn2093-0569
dc.identifier.issue3
dc.identifier.pmid38946696
dc.identifier.scopus2-s2.0-85197588186
dc.identifier.scopusqualityQ2
dc.identifier.startpage233
dc.identifier.urihttps://doi.org/10.3344/kjp.24042
dc.identifier.urihttps://hdl.handle.net/20.500.12418/29377
dc.identifier.volume37
dc.identifier.wosWOS:001267881000003
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherKorean Pain Soc
dc.relation.ispartofKorean Journal of Pain
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectFerroptosis
dc.subjectGanglia
dc.subjectSpinal
dc.subjectGlutathione
dc.subjectMorphine
dc.subjectOxidative Stress
dc.subjectPain
dc.subjectPhospholipid Hydroperoxide Glutathione Peroxidase
dc.titleFerroptosis inhibitor ferrostatin-1 attenuates morphine tolerance development in male rats by inhibiting dorsal root ganglion neuronal ferroptosis
dc.typeArticle

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