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Taurine protects against methotrexate-induced toxicity and inhibits leukocyte death

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dc.contributor.authorYEGEN, BERRAK
dc.contributor.authorsCetiner, M; Sener, G; Sehirli, AO; Eksioglu-Demiralp, E; Ercan, F; Sirvanci, S; Gedik, N; Akpulat, S; Tecimer, T; Yegen, BC
dc.date.accessioned2022-03-12T17:20:46Z
dc.date.available2022-03-12T17:20:46Z
dc.date.issued2005
dc.description.abstractThe efficacy of methotrexate (MTX), a widely used cytotoxic chemotherapeutic agent, is often limited by severe side effects and toxic sequelae. Regarding the mechanisms of these side effects, several hypotheses have been put forward, among which oxidative stress is noticeable. The present study was undertaken to determine whether taurine, a potent free radical scavenger, could ameliorate MTX-induced oxidative injury and modulate immune response. Following a single dose of methotrexate (20 mg/kg), either saline or taurine (50 mg/kg) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the ileum, liver, and kidney were removed to measure malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen content, as well as histological examination. Our results showed that MTX administration increased the MDA, MPO activity, and collagen contents and decreased GSH levels in all tissues (P < 0.001), while these alterations were reversed in taurine-treated group (P < 0.05-0.01). Elevated (P < 0.001) TNF-alpha level observed following MTX treatment was depressed with taurine (P < 0.01). Oxidative burst of neutrophils stimulated by phorbol myristate acetate was reduced in saline-treated MTX group (P < 0.001), while taurine abolished this effect. Similarly, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in MTX-treated animals, while taurine reversed these effects (P < 0.05). Reduced cellularity in bone marrow samples of MTX-treated group (P < 0.01) was reversed back to control levels in taurine-treated rats. Severe degeneration of the intestinal mucosa, liver parenchyma, glomerular, and tubular epithelium observed in saline-treated group was improved by taurine treatment. In conclusion, it appears that taurine protects against methotrexate-induced oxidant organ injury and inhibits leukocyte apoptosis and may be of therapeutic potential in alleviating the systemic side effects of chemotherapeutics. (c) 2005 Published by Elsevier Inc.
dc.identifier.doi10.1016/j.taap.2005.03.009
dc.identifier.eissn1096-0333
dc.identifier.issn0041-008X
dc.identifier.pubmed15890378
dc.identifier.urihttps://hdl.handle.net/11424/228275
dc.identifier.wosWOS:000233378100005
dc.language.isoeng
dc.publisherACADEMIC PRESS INC ELSEVIER SCIENCE
dc.relation.ispartofTOXICOLOGY AND APPLIED PHARMACOLOGY
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectmyeloperoxidase
dc.subjectglutathione
dc.subjectapoptosis
dc.subjectoxidative injury
dc.subjectIN-VITRO
dc.subjectINFLAMMATORY MEDIATORS
dc.subjectLYMPHOBLASTOID-CELLS
dc.subjectOXIDATIVE STRESS
dc.subjectINDUCED DAMAGE
dc.subjectNITRIC-OXIDE
dc.subjectRAT-KIDNEY
dc.subjectMYELOPEROXIDASE
dc.subjectHEPATOTOXICITY
dc.subjectCHLORAMINE
dc.titleTaurine protects against methotrexate-induced toxicity and inhibits leukocyte death
dc.typearticle
dspace.entity.typePublication
local.avesis.ide4aae503-5875-4fea-b3ba-7f0ceef93d8d
local.import.packageSS17
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages12
oaire.citation.endPage50
oaire.citation.issue1
oaire.citation.startPage39
oaire.citation.titleTOXICOLOGY AND APPLIED PHARMACOLOGY
oaire.citation.volume209
relation.isAuthorOfPublicatione4eaf9ac-f8dc-4e2b-b940-895cc906790d
relation.isAuthorOfPublication.latestForDiscoverye4eaf9ac-f8dc-4e2b-b940-895cc906790d

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