The impact of Nrf2/HO-1, caspase-3/Bax/Bcl2 and ATF6/IRE1/PERK/GRP78 signaling pathways in the ameliorative effects of morin against methotrexate-induced testicular toxicity in rats

dc.authorid0000-0001-5608-554X
dc.contributor.authorVarışlı, Behçet
dc.contributor.authorÇağlayan, Cüneyt
dc.contributor.authorKandemir, Fatih Mehmet
dc.contributor.authorGür, Cihan
dc.contributor.authorBayav, Ibrahim
dc.contributor.authorGenç, Aydın
dc.date.accessioned2022-10-03T11:52:52Z
dc.date.available2022-10-03T11:52:52Z
dc.date.issued2022
dc.departmentTıp Fakültesi
dc.description.abstractBackground Methotrexate (MT) is a broadly used chemotherapeutic drug however its clinical use is confronted with several forms of toxicities containing testicular damage. The current study assessed the ameliorative effects of morin on MT-induced testicular damage with the investigation of its mechanism and the potential involvement of oxidative stress, inflammation, apoptosis and endoplasmic reticulum stress in such protection. Methods The animals were divided into 5 distinct groups (7 rats in each group). Group 1 was control group, group 2 received MT-only (20 mg/kg bw), group 3 received orally morin-only (100 mg/kg bw), group 4 received MT (20 mg/kg bw) + morin (50 mg/kg bw) and group 5 received MT (20 mg/kg bw) + morin (100 mg/kg). In this study, morin was administered orally for 10 days, while MT was administered intraperitoneally on the 5th day. Results MT intoxication was linked with augmented MDA while decreased GSH levels, the enzyme activities of glutathione peroxidase, superoxide dismutase, and catalase and mRNA levels of HO-1 and Nrf2 in the testis tissues. MT injection caused inflammation in the testicular tissue via up-regulation of MAPK14, NF kappa B, TNF-alpha and IL-1 beta. MT application also caused apoptosis and endoplasmic reticulum stress in the testis tissue via increasing mRNA transcript levels of Bax, caspase-3, PERK, IRE1, ATF-6, GRP78 and down-regulation of Bcl-2. Conclusion Treatment with morin at a dose of 50 and 100 mg/kg considerably mitigated oxidative stress, inflammation, apoptosis and endoplasmic reticulum stress in the testicular tissue indicating that testicular damage related to MT toxicity could be modulated by morin administration.
dc.identifier.doi10.1007/s11033-022-07873-5
dc.identifier.endpage-en_US
dc.identifier.issn0301-4851
dc.identifier.issn1573-4978
dc.identifier.issue-en_US
dc.identifier.pmid36057755
dc.identifier.scopusqualityQ2
dc.identifier.startpage-en_US
dc.identifier.urihttps:/dx.doi.org/10.1007/s11033-022-07873-5
dc.identifier.urihttps://hdl.handle.net/20.500.12451/9718
dc.identifier.volume-en_US
dc.identifier.wosWOS:000849477400001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofMolecular Biology Reports
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectApoptosis
dc.subjectEndoplasmic Reticulum Stress
dc.subjectMethotrexate
dc.subjectMorin
dc.subjectTesticular Injury
dc.titleThe impact of Nrf2/HO-1, caspase-3/Bax/Bcl2 and ATF6/IRE1/PERK/GRP78 signaling pathways in the ameliorative effects of morin against methotrexate-induced testicular toxicity in rats
dc.typeArticle

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