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Effects of alpha-lipoic acid on skeletal muscle ischemia-reperfusion injury in mice. JOURNAL OF SURGERY AND MEDICINE 2020. [DOI: 10.28982/josam.764953] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Yilmaz Y, Tumkaya L. Effects of hyperbaric oxygen and iloprost on intestinal ischemia-reperfusion induced acute lung injury. Ann Surg Treat Res 2019; 96:34-40. [PMID: 30603632 PMCID: PMC6306501 DOI: 10.4174/astr.2019.96.1.34] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 08/09/2018] [Accepted: 08/29/2018] [Indexed: 11/30/2022] Open
Abstract
Purpose To research the effects of iloprost (IL) and hyperbaric oxygen (HBO) combination treatment on lung injury and on tumor necrosis factor alpha (TNF-α), myeloperoxidase (MPO), malondialdehyde (MDA), and soluble intercellular adhesion molecule-1 (sICAM-1) levels after tissue or organ ischemia-reperfusion, and on ischemia-reperfusion induced lung neutrophil sequestration. Methods Forty white New Zealand rabbits were assigned randomly into 5 groups: HBO, IL, HBO+IL, control, and sham groups. TNF-α values were checked before ischemia, in the 1st hour of ischemia and in the 1st and 4th hours of reperfusion, also at the end of reperfusion period, plasma and tissue MPO values, MDA values, and sICAM-1 levels were detected. After sacrifice, the degree of lung injury was determined by histopathological examination. Results Compared to the control group all therapy groups showed a drastically meaningful reduction in TNF-α increase in 1, 2, and 4 hours. Plasma and lung MDA, MPO, and sICAM-1 levels were significantly lower in IL, HBO, HBO+IL, and sham groups compared with the control group. IL and/or HBO suppressed MDA and MPO increase in the lung tissue and in plasma. Additionally, histopathological score was significantly lower in HBO, IL, HBO+IL, and sham groups than that of the control group. Conclusion Both HBO and IL therapy have a beneficial effect by causing a meaningful reduction in TNF-α production, MPO, MDA, sICAM-1 levels and pulmonary neutrophil sequestration; which play a role, especially, in ischemia reperfusion induced lung damage.
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Affiliation(s)
- Yeliz Yilmaz
- Department of General Surgery, Izmir Katip Celebi University, Ataturk Training and Research Hospital, İzmir, Turkey
| | - Levent Tumkaya
- Department of Histology and Embryology, Recep Tayyip Erdogan University, Faculty of Medicine, Rize, Turkey
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The effect of ozone treatment on remote organ myocardial injury in an aortic ischemia-reperfusion model. TURK GOGUS KALP DAMAR CERRAHISI DERGISI-TURKISH JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 2018; 26:207-213. [PMID: 32082736 DOI: 10.5606/tgkdc.dergisi.2018.15484] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 03/29/2018] [Indexed: 01/24/2023]
Abstract
Background This study aims to investigate the effect of ozone on myocardial ischemia-reperfusion injury occurring after occlusion - reperfusion of infrarenal abdominal aorta in rats. Methods Thirty-two Wistar albino rats (weighing 200-250 g) were randomized into four equal groups. The control (sham) group underwent laparotomy and dissection of the infrarenal abdominal aorta without occlusion. Intraperitoneal ozone was applied for 10 days 1 mg/kg/day in the control+ozone group. Afterwards, control+ozone group underwent laparotomy and dissection of the infrarenal abdominal aorta without occlusion. Aortic ischemia-reperfusion and aortic ischemia-reperfusion+ozone groups underwent dissection of the infrarenal abdominal aorta, followed by achieving ischemia and reperfusion by cross-clamping the infrarenal abdominal aorta for 60 minutes and removing the cross-clamp for 60 minutes, respectively. The tissue levels of malondialdehyde and activity levels of superoxide dismutase, catalase, and myeloperoxidase were measured in the myocardial specimens. The tumor necrosis factor, interleukin-6 and troponin-I levels were measured in the plasma. A histopathological examination of the myocardial specimens was undertaken. Results Biochemical analysis showed that aortic ischemia-reperfusion significantly increased (p<0.05 vs. control) while ozone significantly decreased (p<0.05 vs. aortic ischemia-reperfusion) the myocardial tissue levels of superoxide dismutase and catalase and level of plasma troponin-I. Histologically, in the aortic ischemia-reperfusion group, myocardial disorganization, myofiber swelling and myofiber eosinophilia in the myocardial tissue samples were significantly increased compared to the control group (p<0.05 vs. control). However, histopathological changes in the aortic ischemia-reperfusion+ozone group decreased compared to the aortic ischemia-reperfusion group. Conclusion The results of this experimental study indicate that ozone attenuates myocardial injury and oxidative stress that develop after infrarenal aortic ischemia-reperfusion through three markers; (i) decreased tissue superoxide dismutase and catalase levels, (ii) d ecreased p lasma t roponin-I l evels, a nd (iii) reduced histopathological changes, albeit not statistically significant.
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Gulmen S, Kiris I, Kocyigit A, Kumbul Dogus D, Ceylan BG, Meteoglu I. β-Glucan Protects against Lung Injury Induced by Abdominal Aortic Ischemia-Reperfusion in Rats. J Surg Res 2010; 164:e325-32. [DOI: 10.1016/j.jss.2010.08.013] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2010] [Revised: 07/08/2010] [Accepted: 08/09/2010] [Indexed: 11/16/2022]
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Abstract
OBJECTIVES In this study, the effects of adalimumab (ADA), a fully humanized IgG1 monoclonal antibody to tumor necrosis factor α, on experimentally acute pancreatitis (AP) were examined. METHODS Healthy Wistar rats (n = 32) were randomly divided into 4 groups: group 1, AP; group 2, AP + ADA; group 3, control (physiologic saline), and group 4, physiologic saline + ADA (n = 8/group). Acute pancreatitis was induced with a retrograde injection of 3% sodium (Na)-taurocholate into the common biliopancreatic duct. Adalimumab was simultaneously administered at 50 mg/kg intraperitoneally for groups 2 and 4. Physiologic saline was administered instead of Na-taurocholate for non-AP groups. After 24 hours, serum amylase, lactate dehydrogenase, pancreatic myeloperoxidase, and malondialdehyde activities, along with pancreatic histopathology, were examined. RESULTS Adalimumab treatment significantly decreased serum amylase activity (AP, 2778.25 ± 298.80; AP + ADA, 2143.13 ± 221.69; control, 1541.00 ± 148.39; ADA, 1143.00 ± 256.30 U/L; P < 0.001), lactate dehydrogenase activity (AP, 2978.37 ± 364.65; AP + ADA, 2582.75 ± 164.23; control 931.25 ± 135.93; ADA, 582.62 ± 99.37 U/L; P < 0.001), myeloperoxidase activity (AP, 1.44 ± 0.20; AP + ADA, 0.86 ± 0.01; control, 0.60 ± 0.17; ADA, 0.41 ± 0.00 U/g of wet tissue; P < 0.001), malondialdehyde activity (AP, 16.94 ± 3.98; AP + ADA, 7.66 ± 2.27; control, 9.07 ± 1.00; ADA, 3.58 ± 0.30 nmol/g; P < 0.01), and total histopathologic scores (AP, 2.75 ± 0.16; AP + ADA, 1.50 ± 0.19; control, 0.00 ± 0.00; ADA, 0.00 ± 0.00; P < 0.001). CONCLUSIONS These results support the idea that adalimumab might be beneficial for severity of AP.
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Kara M, Tellioglu G, Sehirli O, Yildar M, Krand O, Berber I, Cetinel S, Eren PA, Sener G, Titiz I. Evaluation of Gadolinium Pre-Treatment with or without Splenectomy in the Setting of Renal Ischemia Reperfusion Injury in Rats. Ren Fail 2009; 31:956-63. [DOI: 10.3109/08860220903216162] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Yilmaz M, Topsakal S, Herek O, Ozmen O, Sahinduran S, Buyukoglu T, Yonetci N. Effects of etanercept on sodium taurocholate-induced acute pancreatitis in rats. Transl Res 2009; 154:241-9. [PMID: 19840765 DOI: 10.1016/j.trsl.2009.07.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2009] [Revised: 07/13/2009] [Accepted: 07/15/2009] [Indexed: 12/22/2022]
Abstract
In this study, we examined the effects of etanercept (ETA) on experimentally induced pancreatitis. Acute pancreatitis was induced with Na taurocholate. ETA was simultaneously administered to treatment groups. Serum amylase and lipase activity, pancreatic histopathology, apoptosis, malondialdehyde (MDA), and myeloperoxidase enzyme activity (MPO) were assessed. Although rats in the groups 1, 2, and 3 were sacrificed 24h later, groups 4, 5, and 6 were sacrificed 5 days later. ETA treatment significantly decreased serum amylase activity (nontreated, 2636.16+/-191.94; treated, 1898.71+/-262.53; control, 506.28+/-17.31 U/L, P<0.001), lipase activity (nontreated, 3049.67+/-972.65; treated, 2538.85+/-660.45; control, 88.57+/-7.54 U/L, P<0.001), histopathologic score (nontreated, 5.43+/-0.43; treated, 2.57+/-0.20; control, 0.71+/-0.18, P<0.001), MDA (nontreated, 105.77+/-13.29; treated, 92.89+/-10.39; control, 41.26+/-2.54 nmol/g, P<0.001), and MPO (nontreated, 0.64+/-1.15; treated, 0.59+/-0.13; control, 0.17+/-0.02 units/g/wet weight, P<0.001) activity in 24-h groups. In 5-day groups, ETA treatment decreased amylase activity (nontreated, 738.67+/-48.60; treated, 497.14+/-47.25; control, 389.00+/-9.17 U/L, P<0.001), lipase activity (nontreated, 101.33+/-39.32; treated, 34.57+/-7.29; control, 23.42+/-2.12 U/L, P<0.001), histopathologic score (nontreated, 5.43+/-0.43; treated, 3.71+/-0.68; control, 0.00+/-0.00, P<0.001), MDA (nontreated, 67.91+/-4.28; treated, 60.91+/-3.57; control, 14.85+/-1.16 nmol/g, P<0.001), and MPO (nontreated, 0.36+/-0.04; treated, 0.27+/-0.02; control, 0.14+/-0.02 units/g/wet weight, P<0.001) activity. Caspase-positive cells numbers around the necrosis significantly decreased by ETA treatment in both 24-h groups (nontreated, 74.28+/-3.26; treated, 67.00+/-1.15; control, 3.85+/-0.63, P<0.001) and 5-day groups (nontreated, 79.85+/-3.01; treated, 47.85+/-5.76; control, 2.22+/-0.63, P<0.001). These results showed that ETA has an ameliorating effect on sodium taurocholate-induced acute necrotic pancreatitis.
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Affiliation(s)
- Mustafa Yilmaz
- Department of Internal Medicine, University of Pamukkale, Denizli, Turkey
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Liu KX, Li YS, Huang WQ, Li C, Liu JX, Li Y. Immediate but not delayed postconditioning during reperfusion attenuates acute lung injury induced by intestinal ischemia/reperfusion in rats: comparison with ischemic preconditioning. J Surg Res 2008; 157:e55-62. [PMID: 19345372 DOI: 10.1016/j.jss.2008.11.843] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2008] [Revised: 11/03/2008] [Accepted: 11/20/2008] [Indexed: 11/29/2022]
Abstract
BACKGROUND A previous study has shown that brief period of repetitive superior mesenteric artery (SMA) occlusion and reperfusion applied at the onset of reperfusion, ischemic postconditioning (IPo), attenuates intestinal injury after intestinal ischemia/reperfusion (II/R). This study tested the hypothesis that IPo would attenuate II/R-induced acute lung injury, which is comparable to ischemic preconditioning (IPC) and the brief period of postconditioning applied at the onset of reperfusion is critical to pulmonary protection by IPo. METHODS Rat II/R injury was produced by clamping SMA for 60 min followed by 60 min of reperfusion. The rats were randomly allocated into one of five groups based upon the intervention (n = 8): sham operation (Sham): sham surgical preparation including isolation of the SMA without occlusion was performed; Injury: there was no intervention either before or after SMA occlusion; ischemia preconditioning (IPC): the SMA was occluded for 10 min followed by 10 min of reperfusion before prolonged occlusion; ischemia postconditioning (IPo): three cycles of 30 sec reperfusion-30 sec reocclusion were imposed immediately upon reperfusion (3 min total intervention); delayed postconditioning: clamping was completely released for full reperfusion for 3 min (the duration of the IPo algorithm), after which three cycles of 30 sec occlusion and reperfusion were applied. RESULTS Histologic results showed severe damage in rat lungs in the injury group evidenced by increased lung wet/dry weight ratio and pulmonary permeability index, which was accompanied by increases in the levels of plasma TNFalpha and IL-6, the pulmonary malondialdehyde (MDA), and the pulmonary myeloperoxidase (MPO) activity and a decrease in superoxide dismutase (SOD) activity. IPo, not delayed IPo, could significantly attenuate lung injury and improve the above variables, which was comparable to IPC. CONCLUSIONS IPo at onset of reperfusion reduces acute lung injury induced by II/R, which may be mediated, in part, by inhibiting oxidant generation, neutrophils filtration, and proinflammatory mediators releases. The early period of reperfusion in the rat model is critical to pulmonary protection by IPo. IPo may improve outcome in clinical conditions associated with II/R.
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Affiliation(s)
- Ke-Xuan Liu
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
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Gulmen S, Kiris I, Narin C, Ceylan BG, Mermi B, Sutcu R, Meteoglu I. Tezosentan reduces the renal injury induced by abdominal aortic ischemia-reperfusion in rats. J Surg Res 2008; 157:e7-e13. [PMID: 19329125 DOI: 10.1016/j.jss.2008.08.011] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2008] [Revised: 07/19/2008] [Accepted: 08/08/2008] [Indexed: 11/16/2022]
Abstract
BACKGROUND Renal injury induced by aortic ischemia-reperfusion (IR) is an important factor in the development of postoperative acute renal failure following abdominal aortic surgery. Endothelin (ET) is involved in the development of renal injury induced by aortic IR and tezosentan (R0 61-0612) is a specific ET receptor antagonist. The aim of this study was to examine the effect of tezosentan on renal injury induced by abdominal aortic IR in rats. MATERIAL AND METHODS Twenty-four Wistar-Albino rats were randomized into three groups (eight per group). Control group underwent laparotomy and dissection of the infrarenal abdominal aorta (IAA) without occlusion. The aortic IR group underwent laparotomy and clamping of the IAA for 120 min followed by 120 min of reperfusion. Aortic IR + tezosentan group underwent same aortic IR periods, and received a bolus intravenous injection of 10 mg/kg tezosentan before ischemia plus continuous intravenous infusion of 1 mg/kg/h tezosentan during 120 min ischemia and 120 min reperfusion. At the end of the experiment, blood and kidney tissue specimens were obtained for biochemical analysis. Histological evaluation of the rat kidney tissues was also done. RESULTS Biochemical analysis showed that aortic IR significantly increased (P < 0.05 versus control) while tezosentan significantly decreased (P < 0.05 versus aortic IR) the tissue levels of malondialdehyde, superoxide dismutase, catalase and myeloperoxidase. Histological analyses showed that aortic IR significantly increased (P < 0.05 versus control) while tezosentan significantly decreased (P < 0.05 versus aortic IR) focal glomerular necrosis, dilatation of Bowman's capsule, degeneration of tubular epithelium, necrosis in tubular epithelium and tubular dilatation in the renal tissue samples. CONCLUSION The results of this study indicate that tezosentan reduces renal injury induced by aortic IR in rats. We think that tezosentan exerted this beneficial effect via reducing oxidative stress and lipid peroxidation, inhibition of leukocyte infiltration into renal tissue and acting cytoprotective on renal tubular cells after aortic IR.
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Affiliation(s)
- Senol Gulmen
- Department of Cardiovascular Surgery, Suleyman Demirel University Medical School, Isparta, Turkey.
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Gao C, Sun X, Zhang G, Zhang H, Zhao H, Yang Y, Han L, Xu L, Chai W. Hyperoxygenated Solution Preconditioning Attenuates Lung Injury Induced by Intestinal Ischemia Reperfusion in Rabbits. J Surg Res 2008; 146:24-31. [DOI: 10.1016/j.jss.2007.07.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2007] [Revised: 07/02/2007] [Accepted: 07/17/2007] [Indexed: 11/24/2022]
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Giakoustidis AE, Giakoustidis DE, Iliadis S, Papageorgiou G, Koliakou K, Kontos N, Taitzoglou I, Botsoglou E, Papanikolaou V, Atmatzidis K, Takoudas D, Antoniadis A. Attenuation of intestinal ischemia/reperfusion induced liver and lung injury by intraperitoneal administration of (-)-epigallocatechin-3-gallate. Free Radic Res 2006; 40:103-10. [PMID: 16298765 DOI: 10.1080/10715760500133479] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
The aim of this study was to evaluate the effect of ( - )-epigallocatechin-3-gallate (EGCG), a natural antioxidant, on liver and lungs after warm intestinal ischemia/reperfusion (I/R). Thirty male Wistar rats were equally divided into a sham-operation group, an intestinal I/R group and an intestinal I/R group pretreated with EGCG intraperitoneally. Intestinal ischemia was induced by occlusion of the superior mesenteric artery for 60 min followed by reperfusion for 120 min. Immediately after reperfusion, liver, lung and blood samples were collected and analyzed. Results showed that intestinal I/R increased the levels of aspartate (AST) and alanine (ALT) transaminase in serum to 987 and 752 IU/l, respectively. Malondialdehyde (MDA) increased in liver to 1.524 nmol/g in the group subjected to intestinal I/R compared to 0.995 nmol/g in the sham operation group. MDA was also increased in lungs to 1.581 nmol/g compared to 0.896 nmol/g in the sham operation group. Myeloperoxidase (MPO) increased in liver, after intestinal I/R, to 5.16 U/g compared to 1.59 U/g in the sham operation group. MPO was also increased in lungs to 3.89 U/g compared to 1.65 U/g in the sham operation group. Pretreatment with EGCG decreased serum levels of AST and ALT to 236 and 178 IU/l, respectively. It also decreased mean MDA levels in liver and lungs to 1.061 and 1.008 nmol/g, respectively, and mean MPO levels in liver and lungs to 1.88 and 1.71 U/g, respectively. Light microscopy and transmission electron microscopy examinations showed significant alteration in liver and lungs and protection of liver and lung parenchyma in the animals treated with EGCG.
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Affiliation(s)
- Alexandros E Giakoustidis
- Department of Transplantation Surgery, Medical School, Hippokration Hospital, Aristotle University, Thessaloniki, Greece
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Liu HB, Cui NQ, Li DH, Chen C. Role of Kupffer cells in acute hemorrhagic necrotizing pancreatitis-associated lung injury of rats. World J Gastroenterol 2006; 12:403-7. [PMID: 16489639 PMCID: PMC4066058 DOI: 10.3748/wjg.v12.i3.403] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the role of Kupffer cells (KCs) in acute hemorrhagic necrotizing pancreatitis-associated lung injury (AHNP-LI).
METHODS: Forty-two rats were allocated to four groups [sham operation, AHNP model, gadolinium chloride (GdCl3) pretreatment, GdCl3 control]. In GdCl3 pretreatment group, GdCl3 was administered by caudal vein injection 24 h before the AHNP model induction. Blood from the iliac artery, alveolar macrophages and tissues from the pancreas and lung, were collected in six animals per group 3 and 6 h after acute pancreatitis induction. TNF-α, IL-1 of serum, myeloperoxidase (MPO) of lung tissue, NF-κB activation of alveolar macrophages were detected. Serum AST and ALT in sham operation group and GdCl3 control group were tested. In addition, histopathological changes of the pancreas and lung were observed under light microscope.
RESULTS: MPO of lung tissue and TNF-α, IL-1 levels of serum were all reduced significantly in GdCl3 pretreatment group compared to those in AHNP group (P <0.01). NF-κB activation of alveolar macrophages was also attenuated significantly in GdCl3 pretreatment group compared to that in AHNP group (P <0.01). The pathological injury of the lung was ameliorated obviously in GdCl3 pretreatment group compared to that in AHNP group. Nevertheless, the serum amylase level did not reduce and injury of the pancreas was not prevented in GdCl3 pretreatment group.
CONCLUSION: Pulmonary injury induced by AHNP is mediated by KC activation and AHNP-LI can be significantly ameliorated by pretreatment with GdCl3 and KCs play a vital role in AHNP-LI.
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Affiliation(s)
- Hong-Bin Liu
- Department of Pharmacology, Tianjin Institute of Acute Abdominal Diseases, No. 122, Sanwei Road, Nankai District, Tianjin 300100, China.
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Abstract
Microvascular dysfunction mediates many of the local and systemic consequences of ischemic-reperfusion (I/R) injury, with a spectrum of changes specific to arterioles, capillaries, and venules. This review discusses the specific changes in the endothelium during I/R injury; describes the differential responses of the various levels of the vasculature including arterioles, capillaries, and venules; and explores mechanisms for remote organ injury. Vascular dysfunction is largely a consequence of changes in the endothelial cells themselves, affecting the integrity of barrier function, cytokine and adhesion molecule expression, and vascular tone. The bioavailability of nitric oxide, an important mediator of vasodilation, is profoundly decreased during the reperfusion period, resulting in impaired vasodilation of arterioles. Release of inflammatory mediators and increased expression of adhesion molecules initiate inflammatory and coagulation cascades that culminate in the occlusion of capillaries, known as the "no-reflow''" phenomenon. In postcapillary venules, the recruitment and transmigration of leukocytes further compromise the integrity of the endothelial barrier and increase the oxidative burden, resulting in leakage and tissue edema. I/R injury can have significant and untoward consequences beyond the affected tissue, with such conditions as systemic inflammatory response syndrome. This review highlights recent progress in understanding of the varied phenomena of vascular dysfunction in I/R injury and some promising advances in the understanding and application of ischemic preconditioning and other potential therapies.
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Affiliation(s)
- John B Seal
- Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA
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Ito K, Ozasa H, Horikawa S. Edaravone protects against lung injury induced by intestinal ischemia/reperfusion in rat. Free Radic Biol Med 2005; 38:369-74. [PMID: 15629865 DOI: 10.1016/j.freeradbiomed.2004.10.029] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2004] [Revised: 10/07/2004] [Accepted: 10/22/2004] [Indexed: 11/18/2022]
Abstract
Intestinal ischemia/reperfusion (I/R) is a critical and triggering event in the development of distal organ dysfunction, frequently involving the lungs. Respiratory failure is a common cause of death and complications after intestinal I/R. In this study we investigated the effects of edaravone (3-methyl-1-phenyl-2-pyrazoline-5-one) on the prevention of lung injury induced by intestinal I/R in rats. Edaravone has been used for protection against I/R injury in patients with cerebral infarction. When rats were subjected to 180 min of intestinal ischemia, a high incidence of mortality was observed within 24 h. In this situation, intravenous administration of edaravone just before the start of reperfusion reduced the mortality in a dose-dependent manner. To examine the efficacy of edaravone on the lung injury induced by intestinal I/R in more detail, we performed 120 min of intestinal ischemia followed by 120 min of reperfusion. Edaravone treatment decreased the neutrophil infiltration, the lipid membrane peroxidation, and the expression of proinflammatory cytokine interleukin-6 mRNA in the lungs after intestinal I/R compared to the I/R-treated rat lungs without edaravone treatment. Histopathological analysis also indicated the effectiveness of edaravone. In conclusion, edaravone ameliorated the lung injury induced by intestinal I/R, resulting in a reduction in mortality.
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Affiliation(s)
- Koji Ito
- Department of Pathological Biochemistry, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062, Japan
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Okutan H, Savas C, Ozguner IF, Yonden Z, Eren VC, Delibas N. Lung injury after aortic occlusion-reperfusion in rats: the role of gadolinium chloride. TOHOKU J EXP MED 2005; 203:267-73. [PMID: 15297731 DOI: 10.1620/tjem.203.267] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Aortic ischemia-reperfusion (AIR) induced lung injury has already been documented. Kupffer cell blockage (KCB) with gadolinium chloride (GdCl3) has also been shown to attenuate remote organ damage caused by ischemia reperfusion. The present study was designed to examine the effect of GdCl3 in lung ischemia-reperfusion injury induced by aortic occlusion. Thirty-two rats were randomly allocated to four groups as follows: SHAM (Sham Laparotomy), SHAM+KCB, AIR, and AIR+KCB. An atraumatic microvascular clamp was placed across the infrarenal abdominal aorta just after its origin from the aorta for 30 minutes. The microvascular clamp on the infrarenal abdominal aorta was removed and reperfused for 60 minutes. GdCl3 was given 24 hours prior to the experiment. Malondialdehyde (MDA) level and myeloperoxidase (MPO) activity were assayed in lung tissues. MDA level and MPO activity in the AIR group were significantly higher than those in the other groups. When compared to AIR group, KCB with GdCl3 significantly decreased MDA level and MPO activity in the AIR+KCB group. These results suggest that GdCl3 attenuates the lung injury caused by AIR. The effects of GdCl3 on reduced lung damage may be mediated through significant decreases in both MDA level and MPO activity.
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Affiliation(s)
- Huseyin Okutan
- Department of Cardiovascular Surgery, Süleyman Demirel University Medical School, Isparta, Turkey.
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Maheshwari A, Christensen RD, Calhoun DA, Dimmitt RA, Lacson A. Circulating CXC-chemokine concentrations in a murine intestinal ischemia-reperfusion model. Fetal Pediatr Pathol 2004; 23:145-57. [PMID: 15768860 DOI: 10.1080/15227950490523781] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
BACKGROUND CXC-chemokines bearing the glutamic acid-leucine-arginine (ELR) motif (ELR+ CXC chemokines) are potent neutrophil chemoattractants and hence may play a role in mucosal injury seen with intestinal ischemia-reperfusion (I/R). METHODS Serum concentrations of ELR+ CXC chemokines (keratinocyte-derived chemokine(KC) / CXC ligand (CXCL) 1, macrophage inflammatory protein (MIP)-2/CXCL 2/3, lipopolysaccharide-induced CXC chemokine (LIX) / CXCL5, and lungkine/CXCL15) were measured in a murine intestinal I/R model. Fifteen 4-week-old wild-type mice were studied in three subgroups: sham, ischemia (superior mesenteric artery [SMA] clamping for 60 min) and ischemia-reperfusion (SMA clamping for 60 min followed by reperfusion for 90 min). RESULTS Concentrations of KC/CXCL1 and MIP-2/CXCL2/3 in sham-treated animals (145 +/- 123 and 107 +/- 55 pg/mL, respectively) and the ischemia subgroup (646 +/- 413 and 226 +/- 129 pg/mL) were similar, but concentrations were signifcantly higher with reperfusion (6398 +/- 2297, p < .001 and 874 +/- 790 pg/mL, p = .04). LIX/CXCL5 and lungkine/CXCL15 concentrations did not change significantly with ischemia or following I/R. KC/CXCL1 and MIP-2/CXCL2/3 concentrations correlated positively with the severity of mucosal injury and with each other, whereas a negative relationship was observed between LIX/CXCL5 concentrations and microscopic injury scores. CONCLUSIONS Development of mucosal injury in intestinal I/R is associated with increased serum concentrations of KC/CXCL1 and MIP-2/CXCL2/3, but not with those of LIX/CXCL5 and lungkine/CXCL15.
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Affiliation(s)
- Akhil Maheshwari
- Department of Pediatrics, University of South Florida College of Medicine, Florida, USA.
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Savas MC, Ozguner M, Ozguner IF, Delibas N. Splenectomy attenuates intestinal ischemia-reperfusion-induced acute lung injury. J Pediatr Surg 2003; 38:1465-70. [PMID: 14577069 DOI: 10.1016/s0022-3468(03)00497-4] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
BACKGROUND/PURPOSE Intestinal ischemia-reperfusion (IIR) induced acute lung injury (ALI) has been documented. Kupffer cell blockage with gadolinium chloride (GdCl(3)) has been shown to attenuate IIR-induced ALI. However, the effects of splenic monocytes/macrophages on IIR-induced ALI has not been studied previously. In the current study, the authors aimed to investigate the role of splenectomy in IIR-induced ALI. METHODS Forty-eight rats were divided randomly into 6 groups as follows: SHAM, SHAM + KCB, SHAM + SPLN, IIR, IIR + KCB, IIR + SPLN. Two hours of ischemia and 1 hour of reperfusion has been applied by clipping the SMA. GdCl3 was given 24 hours before experiment. Splenectomy was done just before SMA clipping. Lung levels of tumor necrosis-factor (TNF), interleukin (IL)-6, myeloperoxidase (MPO), and malondialdehyde (MDA) were assayed biochemically. Lung leukosequestration was determined by counting PMNLs histologically. Kruskal-Wallis and Mann-Whitney U tests were done; P values less than.003 were considered significant. RESULTS Polimorphonuclear leukocyte (PMNL) counts and biochemical parameters in the IIR group were significantly higher than the other groups (P <.003). When compared with IIR group, PMNL counts and biochemical parameters were significantly decreased in the IIR+KCB and IIR+SPLN groups, respectively (P <.003). However, they were still significantly higher than their sham-operated controls (P <.003). CONCLUSIONS This study documents that splenectomy attenuates ALI as well as Kupffer cell blockage. Spleen, an important component of mononuclear phagocytic system as liver Kupffer cells, might play an important role in the IIR-induced ALI.
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Affiliation(s)
- M Cagri Savas
- Department of Pediatric Surgery, Suleyman Demirel University Medical School, Isparta, Turkey
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Naidu BV, Krishnadasan B, Farivar AS, Woolley SM, Thomas R, Van Rooijen N, Verrier ED, Mulligan MS. Early activation of the alveolar macrophage is critical to the development of lung ischemia-reperfusion injury. J Thorac Cardiovasc Surg 2003; 126:200-7. [PMID: 12878956 DOI: 10.1016/s0022-5223(03)00390-8] [Citation(s) in RCA: 100] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
OBJECTIVES Activation of the alveolar macrophage is critical to the development of nonischemic inflammatory lung injury. The present studies were undertaken to determine whether the alveolar macrophage plays a similarly important role in lung ischemia-reperfusion injury. METHODS The left lungs of male rats were rendered ischemic for 90 minutes and reperfused for up to 4 hours. Treated animals received liposome-encapsulated clodronate, which depletes alveolar macrophages. Injury was quantitated in terms of vascular permeability, tissue neutrophil accumulation, and bronchoalveolar lavage fluid leukocyte, chemokine, and cytokine content. Lung homogenates were also analyzed for nuclear translocation of the transcription factors nuclear factor kappaB and activator of protein 1. RESULTS Depletion of alveolar macrophages reduced lung vascular permeability by 53% compared with that seen in control animals (permeability indices: 0.88 +/- 0.07 to 0.46 +/- 0.04, P <.001). The protective effects of alveolar macrophage depletion correlated with a 50% reduction in tissue myeloperoxidase content (0.62 +/- 0.07 to 0.33 +/- 0.03, P <.006) and marked reductions in bronchoalveolar lavage fluid leukocyte accumulation. Alveolar macrophage-depleted animals also demonstrated marked reductions of the elaboration of multiple proinflammatory chemokines and cytokines in the lavage effluent and nuclear transcription factors in lung homogenates. CONCLUSION It is likely that the alveolar macrophage is the key early source of multiple proinflammatory mediators that orchestrate lung ischemia-reperfusion injury. Depleting alveolar macrophages is protective against injury, supporting its central role in oxidant stress-induced cytokine and chemokine release and the subsequent development of lung injury.
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Affiliation(s)
- Babu V Naidu
- Division of Cardiothoracic Surgery, Department of Surgery, University of Washington, Seattle 98195, USA
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Ito K, Ozasa H, Kojima N, Miura M, Iwa T, Senoo H, Horikawa S. Pharmacological preconditioning protects lung injury induced by intestinal ischemia/reperfusion in rat. Shock 2003; 19:462-8. [PMID: 12744491 DOI: 10.1097/01.shk.0000055240.25446.16] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Intestinal ischemia/reperfusion (IIR) is a critical and triggering event in the development of distal organ dysfunction, frequently involving the lungs. Respiratory failure is a common cause of death and complications after intestinal I/R. Stress protein heme oxygenase-1 (HO-1) confers the protection against a variety of oxidant-induced cell and tissue injuries. The aim of this study was to investigate the hypothesis that the induced HO-1 expression by pharmacological preconditioning with anticancer drug doxorubicin (Dox) could protect the lung injury induced by intestinal I/R. Intravenous administration of Dox induced HO-1 expression in the lungs and high levels of the expression were sustained at least to 48 h after the injection. Therefore, as pharmacological preconditioning, a low dose of Dox was injected intravenously into rats at 48 h before the start of intestinal ischemia. Rats underwent intestinal I/R by superior mesenteric artery occlusion for 120 min followed by 120 min of reperfusion. Preconditioning with Dox significantly ameliorated the lung injury induced by the intestinal I/R. Administration of a specific inhibitor of HO activity reduced the efficacy of the preconditioning. Our results suggest that this improvement may be mediated at least in part by the HO-1 induction. These findings may offer interesting perspectives for patient management In Intestinal surgical operation and intestine transplantation.
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Affiliation(s)
- Koji Ito
- Department of Pathological Biochemistry, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 101-0062, Japan
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Börjesson A, Wang X, Sun Z, Inghammar M, Truedsson L, Andersson R. Early treatment with lexipafant, a platelet-activating factor-receptor antagonist, is not sufficient to prevent pulmonary endothelial damage after intestinal ischaemia and reperfusion in rats. Dig Liver Dis 2002; 34:190-196. [PMID: 11990391 DOI: 10.1016/s1590-8658(02)80192-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Intestinal ischaemia-reperfusion can lead to pulmonary injury characterised by increased macromolecular leakage and leukocyte sequestration. Important mediators of ischaemia-reperfusion-associated injury include polymorphonuclear granulocytes and platelet-activating factor. AIM To investigate the potential therapeutic inhibition of platelet-activating factor in intestinal ischaemia-reperfusion associated pulmonary injury, by use of a potent platelet-activating factor-receptor antagonist, lexipafant. METHODS Rats were subjected to 30 minutes of intestinal ischaemia followed by 3 or 12 hours reperfusion. Lexipafant or saline was given intraperitoneally after 30 minutes reperfusion. RESULTS Increased leakage of radiolabelled human serum albumin was found in the lungs after intestinal ischaemia followed by 3 or 12 hours reperfusion. Administration of lexipafant did not significantly prevent the increased leakage. Pulmonary myeloperoxidase content increased after intestinal ischaemia-reperfusion, indicating polymorphonuclear granulocyte sequestration through the pulmonary endothelium. The increase in interleukin-1beta seen after 3 hours reperfusion was partly reversed by lexipafant. CONCLUSIONS Pulmonary injury occurred following intestinal ischaemia-reperfusion, characterised by increased leakage of radiolabelled albumin over the endothelial barrier; correlating with increased pulmonary myeloperoxidase-content, implying involvement of polymorphonuclear granulocytes in the pathogenesis of remote organ injury after intestinal ischaemia-reperfusion. Lexipafant did not significantly decrease severity of pulmonary damage.
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Affiliation(s)
- A Börjesson
- Department of Surgery, Lund University Hospital and Laboratory Medicine, Sweden
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Kong SE, Blennerhassett LR, Heel KA, McCauley RD, Hall JC. Ischaemia-reperfusion injury to the intestine. THE AUSTRALIAN AND NEW ZEALAND JOURNAL OF SURGERY 1998; 68:554-61. [PMID: 9715130 DOI: 10.1111/j.1445-2197.1998.tb02099.x] [Citation(s) in RCA: 125] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Ischaemia-reperfusion injury (IRI) is of obvious relevance in situations where there is an interruption of blood supply to the gut, as in vascular surgery, or in the construction of free intestinal grafts. It is now appreciated that IRI also underlies the guy dysfunction that occurs in early shock, sepsis, and trauma. The events that occur during IRI are complex. However, recent advances in cellular biology have started to unravel these underlying processes. The aim of this review is to provide an outline of current knowledge on the mechanisms and consequences of IRI. Initially, IRI appears to be mediated by reactive oxygen metabolites and, at a later stage, by the priming and activation of polymorphonuclear neutrophils (PMN). Ischaemia-reperfusion injury can diminish the barrier function of the gut, and can promote an increase in the leakage of molecules (intestinal permeability) or the passage of microbes across the wall of the bowel (bacterial translocation). Ischaemia-reperfusion injury to the gut can result in the generation of molecules that may also harm distant tissues.
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Affiliation(s)
- S E Kong
- University Department of Surgery, Royal Perth Hospital, Australia
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