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      How effective are alprostadil and hydrocortisone on reperfusion injury in kidney after distant organ ischemia?

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          Abstract

          Background:

          After reestablishment of blood flow to ischemic limb recirculation of free radicals may cause ischemia-reperfusion injury in many organs. This study designed to investigate effects of hydrocortisone and alprostadil distant injury to kidneys by both measuring biochemical markers of oxidative stress and histopathologic examination in an experimental rat model of hind limb ischemia-reperfusion.

          Materials and Methods:

          This study conducted in Isfahan University of Medical Sciences during 2011–2012. Ischemia was established by infra renal aortic clamping for 60 min in 32 male Wistar rats. Animals were divided into those receiving alprostadil (group ischemia-reperfusion plus alprostadil (IR/A), n = 8), those receiving hydrocortisone (group ischemia-reperfusion plus hydrocortisone (IR/H), n = 8), control group (group ischemia-reperfusion (IR), n = 8), and sham group ( n = 8). After 120 min of reperfusion both kidneys were removed. Levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) as indirect markers of oxidative injury was measured. Finally all data in different groups were compared using the analysis of variance (ANOVA) test by Statistical Package for Social Sciences (SPSS) version 16.

          Results:

          Administration of alprostadil or hydrocortisone does not improve the biochemical parameters of oxidative injury including MDA and SOD. However, statistically significant difference was seen in GSH level among sham and IR groups. Mean (± standard deviation (SD)) concentration of GSH in IR, IR/A, IR/H, and sham groups were 1028.77 (72.65), 924.82 (70.66), 1000.28 (108.77), and 846.69 (163.52), respectively ( P = 0.015). Histopathological study of specimens did not show any significant changes between groups.

          Conclusion:

          Alprostadil and hydrocortisone do not improve the kidney GSH, SOD, and MDA level and kidney releases its GSH reserve during ischemia-reperfusion event, and another point is that, 3 h of ischemia-reperfusion does not develop injury in kidney.

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          Most cited references18

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          Malondialdehyde determination as index of lipid peroxidation.

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            Pathophysiology of ischaemia-reperfusion injury.

            Reperfusion of ischaemic tissues is often associated with microvascular dysfunction that is manifested as impaired endothelium-dependent dilation in arterioles, enhanced fluid filtration and leukocyte plugging in capillaries, and the trafficking of leukocytes and plasma protein extravasation in postcapillary venules. Activated endothelial cells in all segments of the microcirculation produce more oxygen radicals, but less nitric oxide, in the initial period following reperfusion. The resulting imbalance between superoxide and nitric oxide in endothelial cells leads to the production and release of inflammatory mediators (e.g. platelet-activating factor, tumour necrosis factor) and enhances the biosynthesis of adhesion molecules that mediate leukocyte-endothelial cell adhesion. Some of the known risk factors for cardiovascular disease (hypercholesterolaemia, hypertension, and diabetes) appear to exaggerate many of the microvascular alterations elicited by ischaemia and reperfusion (I/R). The inflammatory mediators released as a consequence of reperfusion also appear to activate endothelial cells in remote organs that are not exposed to the initial ischaemic insult. This distant response to I/R can result in leukocyte-dependent microvascular injury that is characteristic of the multiple organ dysfunction syndrome. Adaptational responses to I/R injury have been demonstrated that allow for protection of briefly ischaemic tissues against the harmful effects of subsequent, prolonged ischaemia, a phenomenon called ischaemic preconditioning. There are two temporally and mechanistically distinct types of protection afforded by this adaptational response, i.e. acute and delayed preconditioning. The factors (e.g. protein kinase C activation) that initiate the acute and delayed preconditioning responses appear to be similar; however the protective effects of acute preconditioning are protein synthesis-independent, while the effects of delayed preconditioning require protein synthesis. The published literature in this field of investigation suggests that there are several potential targets for therapeutic intervention against I/R-induced microvascular injury. Copyright 2000 John Wiley & Sons, Ltd.
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              Evaluation of the Antioxidant Potential of Salvia miltiorrhiza Ethanol Extract in a Rat Model of Ischemia-Reperfusion Injury

              The present study was undertaken to evaluate the protection potential of ethanol extract of Salvia miltiorrhiza (SMEE) against oxidative injury in the ischemia-reperfusion (I/R) model of rats in vivo. Rats were divided into six groups of 10 rats each. Group I/R model and sham were fed with a standard rat chow, groups SMEE I and SMEE II were fed with a standard rat chow and 400 or 800 mg/kg b.w. ethanol extract for 12 days before the beginning of I/R studies. Positive control group was fed with a standard rat chow and salvianolic acid B (55 mg/kg b.w.) or tanshinone II-A (55 mg/kg b.w.) for 12 days before the beginning of I/R studies. To produce I/R, the left anterior descending artery (LAD) was occluded in anesthetized rats for 15 min, followed by 120 min reperfusion. Infarct sizes were found significantly decreased in SMEE-treated and positive control groups compared to I/R model group. Serum AST, LDH and CK-MB activities were significantly reduced and myocardium Na+-K+ ATPase, Ca2+-Mg2+ ATPase activities and antioxidant enzyme activities (SOD, CAT, GSH-Px) were markedly increased in SMEE-treated and salvianolic acid B or tanshinone II-A positive control groups compared to the I/R model group. Pretreatment of S. miltiorrhiza ethanol extract and salvianolic acid B or tanshinone II-A dose-dependently reduced significantly myocardium MDA level, ROS and NOS activities and enhanced myocardium GSH level in I/R rats compared to I/R rats model. In conclusion, we clearly demonstrated that S. miltiorrhiza ethanol extract pretreatment can decrease oxidative injury in rats subjected to myocardial I/R.
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                Author and article information

                Journal
                J Res Med Sci
                J Res Med Sci
                JRMS
                Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences
                Medknow Publications & Media Pvt Ltd (India )
                1735-1995
                1735-7136
                September 2013
                : 18
                : 9
                : 755-758
                Affiliations
                [1 ]Department of Plastic Surgery, Trauma Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
                [2 ]Department of Vascular Surgery, Isfahan University of Medical Sciences, Isfahan, Iran
                [3 ]Physiology/Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
                [4 ]Department of Pathology, Isfahan University of Medical Sciences, Isfahan, Iran
                Author notes
                Address for correspondence: Prof. Fereshteh Salimi, Department of Vascular Surgery, Soffeh St, Isfahan, Iran. post code: 8174675731 E-mail: f_salimi@ 123456med.mui.ac.ir
                Article
                JRMS-18-755
                3872582
                24381617
                88e7fd4e-21de-484b-b252-4e4d9f0fff58
                Copyright: © Journal of Research in Medical Sciences

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 June 2013
                : 06 July 2013
                : 26 July 2013
                Categories
                Original Article

                Medicine
                alprostadil,hydrocortisone,ischemia-reperfusion injury,oxidative stress
                Medicine
                alprostadil, hydrocortisone, ischemia-reperfusion injury, oxidative stress

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