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An experimental study on effects of pyrrolidine dithiocarbamate on ischemia-reperfusion injury in testis.

ABSTRACT: INTRODUCTION:The aim of this experimental study was to investigate the histopathological and biochemical effects of pyrrolidine dithiocarbamate, an antioxidant and inhibitor of NF-k?, on ischemiareperfusion injury in rats. METHODS:A total of 21 male Wistar-Albino rats were randomly distributed into three groups as sham group (Group 1), ischemia-reperfusion (I/R) group (Group 2) and I/R with pyrrolidine dithiocarbamate (PDTC) group (Group 3). Left testicles of rats in Groups 2 and 3 underwent testicular torsion of 720° for four hours and 100 mg/kg of PDTC was administered intraperitoneally prior to detorsion in Group 3. An hour after detorsion process, left orchiectomies were performed and 5 ml of intracardiac blood samples were drawn from rats in all three groups. Histopathological examination of testis tissues performed and measurement of superoxide dismutase (SOD) and malondialdehyde (MDA) levels in blood samples were taken. RESULTS:Elevated levels of MDA and decreased SOD activity, together with decreased Johnson tubular biopsy scores consistent with I/R injury were observed in Group 2 (p<0.05). Group 1 and Group 3 were similar in terms of MDA levels, SOD activity, and Johnson scores (p>0.05). CONCLUSIONS:Our results indicated that PDTC may have beneficial effects for alleviation of I/R injury in testicular tissue in rats. Understanding the underlying mechanisms and exploration of its diagnostic and therapeutic potential requires further randomized, controlled trials on a larger scale.

SUBMITTER: Kemahli E

PROVIDER: S-EPMC4907771 | biostudies-other | 2016 Mar-Apr

REPOSITORIES: biostudies-other

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An experimental study on effects of pyrrolidine dithiocarbamate on ischemia-reperfusion injury in testis.

Kemahli Eray E Yildiz Mevlüt M Firat Tülin T Özyalvaçli Mehmet Emin ME Üyetürk Uğur U Yilmaz Burak B Gücük Adnan A

Canadian Urological Association journal = Journal de l'Association des urologues du Canada 20160301 3-4

<h4>Introduction</h4>The aim of this experimental study was to investigate the histopathological and biochemical effects of pyrrolidine dithiocarbamate, an antioxidant and inhibitor of NF-kβ, on ischemiareperfusion injury in rats.<h4>Methods</h4>A total of 21 male Wistar-Albino rats were randomly distributed into three groups as sham group (Group 1), ischemia-reperfusion (I/R) group (Group 2) and I/R with pyrrolidine dithiocarbamate (PDTC) group (Group 3). Left testicles of rats in Groups 2 and ...[more]

PMID: 27330576

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Project description:BACKGROUND:Although early reperfusion is the most desirable intervention after ischemic myocardial insult, it may add to damage through oxidative stress. OBJECTIVES:This study investigated the cardioprotective effects of a single intravenous dose of heat shock protein-72 (HSP72) coupled to a single-chain variable fragment (Fv) of monoclonal antibody 3E10 (3E10Fv) in a rabbit ischemia-reperfusion model. The Fv facilitates rapid transport of HSP72 into cells, even with intact membranes. METHODS:A left coronary artery occlusion (40 min) reperfusion (3 h) model was used in 31 rabbits. Of these, 12 rabbits received the fusion protein (Fv-HSP72) intravenously. The remaining 19 control rabbits received a molar equivalent of 3E10Fv alone (n = 6), HSP72 alone (n = 6), or phosphate-buffered saline (n = 7). Serial echocardiographic examinations were performed to assess left ventricular function before and after reperfusion. Micro-single-photon emission computed tomography imaging of 99mTc-labeled annexin-V was performed with micro-computed tomography scanning to characterize apoptotic damage in vivo, followed by gamma counting of the excised myocardial specimens to quantify cell death. Histopathological characterization of the myocardial tissue and sequential cardiac troponin I measurements were also undertaken. RESULTS:Myocardial annexin-V uptake was 43% lower in the area at risk (p = 0.0003) in Fv-HSP72-treated rabbits compared with control animals receiving HSP72 or 3E10Fv alone. During reperfusion, troponin I release was 42% lower and the echocardiographic left ventricular ejection fraction 27% higher in the Fv-HSP72-treated group compared with control animals. Histopathological analyses confirmed penetration of 3E10Fv-containing molecules into cardiomyocytes in vivo, and treatment with Fv-HSP72 showed fewer apoptotic nuclei compared with control rabbits. CONCLUSIONS:Single-dose administration of Fv-HSP72 fusion protein at the time of reperfusion reduced myocardial apoptosis by almost one-half and improved left ventricular functional recovery after myocardial ischemia-reperfusion injury in rabbits. It might have potential to serve as an adjunct to early reperfusion in the management of myocardial infarction.

Project description:Lixisenatide is a glucagon-like peptide-1 analog which stimulates insulin secretion and inhibits glucagon secretion and gastric emptying. We investigated cardioprotective effects of lixisenatide in rodent models reflecting the clinical situation.The acute cardiac effects of lixisenatide were investigated in isolated rat hearts subjected to brief ischemia and reperfusion. Effects of chronic treatment with lixisenatide on cardiac function were assessed in a modified rat heart failure model after only transient coronary occlusion followed by long-term reperfusion. Freshly isolated cardiomyocytes were used to investigate cell-type specific mechanisms of lixisenatide action.In the acute setting of ischemia-reperfusion, lixisenatide reduced the infarct-size/area at risk by 36% ratio without changes on coronary flow, left-ventricular pressure and heart rate. Treatment with lixisenatide for 10 weeks, starting after cardiac ischemia and reperfusion, improved left ventricular end-diastolic pressure and relaxation time and prevented lung congestion in comparison to placebo. No anti-fibrotic effect was observed. Gene expression analysis revealed a change in remodeling genes comparable to the ACE inhibitor ramipril. In isolated cardiomyocytes lixisenatide reduced apoptosis and increased fractional shortening. Glucagon-like peptide-1 receptor (GLP1R) mRNA expression could not be detected in rat heart samples or isolated cardiomyocytes. Surprisingly, cardiomyocytes isolated from GLP-1 receptor knockout mice still responded to lixisenatide.In rodent models, lixisenatide reduced in an acute setting infarct-size and improved cardiac function when administered long-term after ischemia-reperfusion injury. GLP-1 receptor independent mechanisms contribute to the described cardioprotective effect of lixisenatide. Based in part on these preclinical findings patients with cardiac dysfunction are currently being recruited for a randomized, double-blind, placebo-controlled, multicenter study with lixisenatide.(ELIXA, ClinicalTrials.gov Identifier: NCT01147250).

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An experimental study on effects of pyrrolidine dithiocarbamate on ischemia-reperfusion injury in testis.

Publications

An experimental study on effects of pyrrolidine dithiocarbamate on ischemia-reperfusion injury in testis.

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