The Effects of Sirolimus on Target Organs During Mesenteric Ischemia and Reperfusion Damage in an Experimental Rat Model

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dc.authoridUmit, Hasan/0000-0002-3651-4180
dc.authorwosidUmit, Hasan/T-6236-2019
dc.contributor.authorSagiroglu, Tamer
dc.contributor.authorSezer, Atakan
dc.contributor.authorAltaner, Semsi
dc.contributor.authorUmit, Hasan
dc.contributor.authorYalta, Tulin
dc.contributor.authorYagci, Mehmet Ali
dc.date.accessioned2024-06-12T11:01:37Z
dc.date.available2024-06-12T11:01:37Z
dc.date.issued2011
dc.departmentTrakya Üniversitesien_US
dc.description.abstractBACKGROUND: Mesenteric ischemia and reperfusion (I/R) syndrome (MIRS) has been considered a clinicopathologic entity associated with a variety of clinically severe conditions with decreased intestinal blood flow and has been known to induce I/R damage in various organs. Sirolimus (SRL), a macrolide antibiotic isolated from a strain of Streptomyces hygroscopicus, is a potent and nonnephrotoxic immunosuppressant. OBJECTIVE: This study was designed to investigate the potential impact of sirolimus on MIRS-induced I/R damage in renal, intestinal, pulmonary, and hepatic tissues in an experimental rat model. METHODS: Twenty-four male Sprague-Dawley rats, aged 6 to 8 weeks and weighing 280 (+/- 20 g), were studied. Using computer-generated random numbers, rats were assigned to 1 of the following 3 groups: group 1 (I/R group, n = 8), group 2 (I/R + sirolimus group, n = 8), and group 3 (control group, n = 8). Sirolimus, in a 1 mg/mL (60 mL) solution, was administered intraperitoneally in a dose of 1.5 mg/kg/d to the rats assigned to group 2 starting from 3 days before the surgical procedure. In surgery, a laparotomy was performed to clamp the superior mesenteric artery and, thus, induce bowel ischemia in groups 1 and 2. After 60 minutes of ischemia, the microvascular clamp on the superior mesenteric artery was removed for 3 hours of reperfusion. Soon after experimental induction of MIRS, bowel, lung, kidney, and liver specimens from each animal were harvested for both biochemical and histopathologic analysis. RESULTS: There were statistically significant differences between groups 1 and 3 with regard to degrees of intestinal (P < 0.001), hepatic (P = 0.001), renal (P < 0.001), and pulmonary (P = 0.01) I/R damage. The lung specimens from group 2 had less inflammation and perivascular edema formation compared with specimens from group 1, but no statistical significance was observed between the groups (P < 0.33). There were statistically significant differences between groups 1 and 2 with regard to degrees of intestinal, hepatic, and renal I/R damage (P = 0.001 for all). CONCLUSION: The findings of the present study demonstrate the attenuating effects of sirolimus on I/R damage in the intestine and remote organs, including the liver and kidney in the setting of MIRS in an experimental rat model. As a therapeutic implication, the utility of sirolimus may be of clinical value in procedures associated with a high likelihood of I/R damage, including major abdominal operations and renal transplantation. However, whether these results apply to humans is unclear. Additional experimental and clinical studies are warranted to confirm the clinical utility of sirolimus in conditions potentially associated with I/R damage. (Curr T her Res Clin Exp. 2011;72:79-93) (C) 2011 Elsevier HS Journals, Inc. All rights reserved.en_US
dc.identifier.doi10.1016/j.curtheres.2011.03.004
dc.identifier.endpage93en_US
dc.identifier.issn0011-393X
dc.identifier.issn1879-0313
dc.identifier.issue2en_US
dc.identifier.pmid24648578en_US
dc.identifier.scopus2-s2.0-79955726272en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage79en_US
dc.identifier.urihttps://doi.org/10.1016/j.curtheres.2011.03.004
dc.identifier.urihttps://hdl.handle.net/20.500.14551/20967
dc.identifier.volume72en_US
dc.identifier.wosWOS:000291179800004en_US
dc.identifier.wosqualityQ4en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevier Science Incen_US
dc.relation.ispartofCurrent Therapeutic Research-Clinical And Experimentalen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectExperimental Modelen_US
dc.subjectIschemia Reperfusion Damageen_US
dc.subjectSirolimusen_US
dc.subjectTarget Organsen_US
dc.subjectIntestinal Ischemia/Reperfusion Injuryen_US
dc.subjectRapamycinen_US
dc.subjectCyclosporineen_US
dc.subjectFibrosisen_US
dc.subjectPreservationen_US
dc.subjectInhibitionen_US
dc.subjectPerfusionen_US
dc.subjectRecoveryen_US
dc.titleThe Effects of Sirolimus on Target Organs During Mesenteric Ischemia and Reperfusion Damage in an Experimental Rat Modelen_US
dc.typeArticleen_US

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