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The blockade of the renin-angiotensin system reverses tacrolimus related cardiovascular toxicity at the histopathological level

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dc.contributor.authorTUĞLULAR, ZÜBEYDE SERHAN
dc.contributor.authorsAgirbasli, Mehmet; Papila-Topal, Nurdan; Ogutmen, Betul; Deniz, Hicran; Cakalagaoglu, Fulya; Tuglular, Serhan; Akoglu, Emel
dc.date.accessioned2022-03-14T09:03:17Z
dc.date.available2022-03-14T09:03:17Z
dc.date.issued2007-06
dc.description.abstractIntroduction. In this study, we investigate the toxic effects of tacrolimus (FK506) on the cardiovascular system at the histopathological level in a rat model and whether these effects can be reversed by the blockade of the renin-angiotensin system (RAS) by either an angiotensin-converting enzyme inhibitor (ACE-inhibitors) or an angiotensin receptor antagonist (ARB). Methods and results. Thirty-one Wistar rats were divided into four groups. FK506 group was treated with FK506 intraperitoneally (i.p.), FK506+ACE-inhibitors and FK506+ARB groups were treated with either quinapril or valsartan orally in addition to FK506. Control group was treated with saline i.p. Histological and immunohistochemical staining of cardiovascular tissue in the FK506 group showed increased vacuolar degeneration (11.2 vs. 5.8, p=0.008), arterial hyalinosis (10.7 vs. 6.3, p=0.036), transforming growth factor-beta (TGF-P) (12.2 vs. 4.8, p=0.001) and vascular endothelial growth factor expression (VEGF) (10.7 vs. 6.3, p=0.036), elastic van Gieson (11.5 vs. 5.5, p=0.004), and periodic acid Schiff stain scores (12.5 vs. 4.5, p < 0.001) compared to the control group. Immunoihistochemical scores showed that expression of TGF-P is up-regulated, and bone morphogenic protein (BMP-7) is down-regulated with FK506 toxicity.Adding RAS blockade with either an ACE-inhibitor or an ARB could reverse FK506 induced changes. Both FK506+ACE-inhibitors and FK506+ARB groups demonstrated decrease in arterial hyalinosis (22.1 vs. 14.4 (FK5o6+ACE-inhibitor) and 13.6 (FK506+ARB), p=0.09) and vacuolar degeneration (23.1 vs. 16.1 (FK506+ACEinhibitor) and 12.4 (FK506+ARB), p=0.006) scores compared to the FK506 group. Conclusion. Blockade of RAS could reverse the histopathological signs of FK506 induced cardiac toxicity in a rat model.
dc.identifier.doi10.3317/jraas.2007.009
dc.identifier.issn1470-3203
dc.identifier.pubmed17703430
dc.identifier.urihttps://hdl.handle.net/11424/242248
dc.identifier.wosWOS:000248696000002
dc.language.isoeng
dc.publisherJ R A A S LTD
dc.relation.ispartofJOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjecttacrolimus
dc.subjectcardiac toxicity
dc.subjectrenin-angiotensin system
dc.subjectGROWTH-FACTOR-BETA
dc.subjectMESANGIAL CELLS
dc.subjectTGF-BETA
dc.subjectTRANSPLANT RECIPIENT
dc.subjectFK506 NEPHROTOXICITY
dc.subjectDIABETES-MELLITUS
dc.subjectCYCLOSPORINE-A
dc.subjectRATS
dc.subjectEXPRESSION
dc.subjectFIBROSIS
dc.titleThe blockade of the renin-angiotensin system reverses tacrolimus related cardiovascular toxicity at the histopathological level
dc.typearticle
dspace.entity.typePublication
local.avesis.id06fd7339-5fa8-4b0f-ae90-5fe5b813306b
local.import.packageSS16
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages5
oaire.citation.endPage58
oaire.citation.issue2
oaire.citation.startPage54
oaire.citation.titleJOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
oaire.citation.volume8
relation.isAuthorOfPublication3ea0c6f9-3408-46b6-b382-144ccbf7bc72
relation.isAuthorOfPublication.latestForDiscovery3ea0c6f9-3408-46b6-b382-144ccbf7bc72

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