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Estrogen receptor agonists protect against acetaminophen-induced hepatorenal toxicity in rats

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dc.contributor.authorYILDIRIM, ALPER
dc.contributor.authorsKoyuncuoglu, Turkan; Yildirim, Alper; Dertsiz, Ekin K.; Yuksel, Meral; Ercan, Feriha; Yegen, Berrak C.
dc.date.accessioned2022-03-12T22:40:30Z
dc.date.available2022-03-12T22:40:30Z
dc.date.issued2020
dc.description.abstractAims: Acetaminophen-induced hepatorenal toxicity varies among sexes with controversial results among species. The aim was to compare the impact of sex and ovarian hormones on hepatorenal toxicity and to elucidate protective effects of estrogen and estrogen receptor (ER) agonists. Main methods: Under anesthesia, female rats underwent ovariectomy (OVX) or sham-OVX. Starting at postsurgical 40th day, OVX-rats received subcutaneously (each, 1 mg/kg/day) 17 beta-estradiol (E2), ER beta-agonist (DPN) or ER alpha-agonist (PPT) for 10 days, while male and sham-OVX rats received vehicle for 10 days. Then, rats received either acetaminophen (3 g/kg) or saline by orogastric gavage and were decapitated at 24th h. Blood samples were obtained to measure serum ALT, AST, BUN, creatinine levels. Liver and kidney samples were obtained for histopathologic examination and for analyzing levels of luminoland lucigenin-chemiluminescence, glutathione and myeloperoxidase activity. Key findings: Compared to their control groups, levels of AST, ALT, BUN, creatinine, hepatic and renal myeloperoxidase activity and chemiluminescence levels were increased, and hepatic glutathione level was decreased in acetaminophen-administered male groups, while ALT and hepatic chemiluminescence levels were not elevated in sham-OVX-rats. Both ER-agonists and E2 reduced BUN, creatinine and reversed all oxidative parameters in renal tissues of OVX-rats. Additionally, ER alpha-agonist reversed all hepatic injury parameters, while ER beta-agonist elevated hepatic glutathione level. Significance: Acetaminophen toxicity in female rats presented with a more preserved hepatic function, while renal toxicity was not influenced by sex or by the lack of ovarian hormones. Pretreatment with estrogen or ER agonists, via their antioxidant actions, provided protective effects on acetaminophen-induced hepatorenal toxicity.
dc.identifier.doi10.1016/j.lfs.2020.118561
dc.identifier.eissn1879-0631
dc.identifier.issn0024-3205
dc.identifier.pubmed33045213
dc.identifier.urihttps://hdl.handle.net/11424/235973
dc.identifier.wosWOS:000598131200009
dc.language.isoeng
dc.publisherPERGAMON-ELSEVIER SCIENCE LTD
dc.relation.ispartofLIFE SCIENCES
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectAcetaminophen
dc.subjectEstrogen receptor agonists
dc.subjectOxidative stress
dc.subjectHepatorenal toxicity
dc.titleEstrogen receptor agonists protect against acetaminophen-induced hepatorenal toxicity in rats
dc.typearticle
dspace.entity.typePublication
local.avesis.id6796baac-9d43-4c0e-8ba9-93f4100467b9
local.import.packageSS17
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.articlenumber118561
local.journal.numberofpages11
local.journal.quartileQ1
oaire.citation.titleLIFE SCIENCES
oaire.citation.volume263
relation.isAuthorOfPublication1840e6a0-5ec8-42b9-bca3-4e891749ac77
relation.isAuthorOfPublication.latestForDiscovery1840e6a0-5ec8-42b9-bca3-4e891749ac77

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