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Brouwers K, van Geel SRWM, van Midden D, Kruit AS, Kusters B, Hummelink S, Ulrich DJO. Added Value of Histological Evaluation of Muscle Biopsies in Porcine Vascularized Composite Allografts. J Clin Med 2024; 13:5167. [PMID: 39274379 PMCID: PMC11395792 DOI: 10.3390/jcm13175167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 07/31/2024] [Accepted: 08/27/2024] [Indexed: 09/16/2024] Open
Abstract
Background: Machine perfusion (MP) offers extended preservation of vascularized complex allografts (VCA), but the diagnostic value of histology using hematoxylin and eosin (H&E) in detecting ischemia-reperfusion injury (IRI) in muscle cells remains unclear. This study aims to document the application of the Histology Injury Severity Score (HISS) and to assess whether additional staining for nicotinamide adenine dinucleotide (NADH) and membrane attack complex (MAC) improves IRI detection in a porcine limb replantation model. Methods: The forelimbs of 16 Dutch Landrace pigs were amputated and preserved for 24 h using hypothermic MP (n = 8) with Histidine-Tryptophan-Ketoglutarate (HTK) or for 4 h with SCS (n = 8) before heterotopic replantation and 7 days of follow-up. Muscle damage was assessed via biochemical markers and light microscopy using H&E, NADH, and MAC at baseline, post-intervention, and post-operative day (POD) 1, 3, and 7 timepoints, using the HISS and a self-developed NADH and MAC score. Results: H&E effectively identified damaged muscle fibers and contributed to IRI assessment in porcine limbs (p < 0.05). The highest HISS was measured on POD 3 between MP (4.9) and SCS (3.5) (p = 0.029). NADH scores of both preservation groups varied over the 7-day follow-up and were statistically insignificant compared with baseline measurements (p > 0.05). MAC revealed no to minimal necrotic tissue across the different timepoints. Conclusions: This study documents the application of the HISS with H&E to detect IRI in muscle fibers. NADH and MAC showed no significant added diagnostic utility. The 24 h MP showed similar muscle alterations using the HISS compared to that of the 4 h SCS after a 7-day follow up.
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Affiliation(s)
- Kaj Brouwers
- Department of Plastic and Reconstructive Surgery, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
| | - Shannen R W M van Geel
- Department of Plastic and Reconstructive Surgery, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
| | - Dominique van Midden
- Department of Pathology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
| | - Anne Sophie Kruit
- Department of Plastic and Reconstructive Surgery, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
| | - Benno Kusters
- Department of Pathology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
| | - Stefan Hummelink
- Department of Plastic and Reconstructive Surgery, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
| | - Dietmar J O Ulrich
- Department of Plastic and Reconstructive Surgery, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
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Huang ZH, Dong MQ, Liu FY, Zhou WJ. Dynamics of glutamine synthetase expression in hepatic ischemia-reperfusion injury: Implications for therapeutic interventions. World J Hepatol 2024; 16:1177-1184. [PMID: 39323976 PMCID: PMC11423427 DOI: 10.4254/wjh.v16.i8.1177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 07/09/2024] [Accepted: 07/25/2024] [Indexed: 08/21/2024] Open
Abstract
BACKGROUND Hepatic ischemia-reperfusion injury (IRI) poses a great challenge in liver surgery and transplantation because of oxidative stress and inflammatory responses. The changes in glutamine synthetase (GS) expression during hepatic IRI remain unclear. AIM To investigate the dynamic expression of GS during hepatic IRI. METHODS Following hepatic ischemia for 1 h and reperfusion, liver tissue samples were collected at 0.5, 6, and 24 hours postreperfusion for fixation, embedding, sectioning. Hematoxylin and eosin staining and GS staining were performed. RESULTS GS expression rapidly decreases in hepatocytes around the central vein after IRI, reaching its lowest point at 6 hours postreperfusion, and then gradually recovers. CONCLUSION GS is highly sensitive to IRI, highlighting its potential role as an indicator of liver injury states and a target for therapeutic intervention.
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Affiliation(s)
- Zhi-Hao Huang
- State Key Laboratory of Organ Failure Research, Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Meng-Qi Dong
- State Key Laboratory of Organ Failure Research, Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Feng-Yong Liu
- Department of Interventional Radiology, Senior Department of Oncology, Fifth Medical Center of PLA General Hospital, Beijing 100853, China
| | - Wei-Jie Zhou
- State Key Laboratory of Organ Failure Research, Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
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Meng HH, Liu WY, Zhao WL, Zheng Q, Wang JS. Study on the acute toxicity of trichlorfon and its breakdown product dichlorvos to goldfish (Carassius auratus) based on 1H NMR metabonomics. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:125664-125676. [PMID: 38001290 DOI: 10.1007/s11356-023-31012-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 11/07/2023] [Indexed: 11/26/2023]
Abstract
Trichlorfon, one of the most widely used organophosphate insecticides, is commonly employed in aquaculture and agriculture to combat parasitic infestations. However, its inherent instability leads to rapid decomposition into dichlorvos (DDVP), increasing its toxicity by eightfold. Therefore, the environmental effects of trichlorfon in real-world scenarios involve the combined effects of trichlorfon and its degradation product, DDVP. In this study, we systematically investigated the degradation of trichlorfon in tap water over time using HPLC and LC-MS/MS analysis. Subsequently, an experiment was conducted to assess the acute toxicity of trichlorfon and DDVP on goldfish (Carassius auratus), employing a 1H NMR-based metabolic approach in conjunction with serum biochemistry, histopathological inspection, and correlation network analysis. Exposure to trichlorfon and its degradation product DDVP leads to increased lipid peroxidation, reduced antioxidant activity, and severe hepatotoxicity and nephrotoxicity in goldfish. Based on the observed pathological changes and metabolite alterations, short-term exposure to trichlorfon significantly affected the liver and kidney functions of goldfish, while exerting minimal influence on the brain, potentially due to the presence of the blood-brain barrier. The changes in the metabolic profile indicated that trichlorfon and DDVP influenced several pathways, including oxidative stress, protein synthesis, energy metabolism, and nucleic acid metabolism. This study demonstrated the applicability and potential of 1H NMR-based metabonomics in pesticide environmental risk assessment, providing a feasible method for the comprehensive study of pesticide toxicity in water environments.
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Affiliation(s)
- Hui-Hui Meng
- Center of Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing, 210094, China
| | - Wen-Ya Liu
- Center of Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing, 210094, China
| | - Wen-Long Zhao
- Center of Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing, 210094, China
| | - Qi Zheng
- Center of Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing, 210094, China
| | - Jun-Song Wang
- Center of Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing, 210094, China.
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24-hour Perfusion of Porcine Myocutaneous Flaps Mitigates Reperfusion Injury: A 7-day Follow-up Study. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2022; 10:e4123. [PMID: 35211366 PMCID: PMC8860339 DOI: 10.1097/gox.0000000000004123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 12/03/2021] [Indexed: 11/26/2022]
Abstract
Background: Static cold storage is the gold standard of preservation in vascularized composite allotransplantation and allows a preservation time of 4–6 hours. Machine preservation is a promising technique for prolonged preservation; however, studies on extended preservation that compare different preservatives are scarce. This study aims to assess the feasibility of 24-hour acellular perfusion and compares different preservation solutions in a porcine myocutaneous flap replantation model. Methods: Six harvested bilateral myocutaneous flaps of three Dutch Landrace pigs were perfused hypothermically for 24 hours with University of Wisconsin machine perfusion solution (UW-MPS; n = 2) or histidine-tryptophan-ketoglutarate solution (HTK; n = 2) or preserved on ice for 4 hours (n = 2) before orthotopic replantation. Animals were observed for 7 days after replantation. Skeletal muscle injury was assessed by biochemical markers during perfusion, and muscle biopsies were analyzed for ischemia reperfusion injury directly after preservation and at 1, 3, and 7 days after replantation. Results: Markers of muscle damage varied during perfusion, but decreased overall in both perfusion groups. Flap weight increased 60% and 97% in the HTK-perfused flaps, compared with -6% and -7% in the UW-MPS-perfused flaps after 24 hours. Histopathologic evaluation demonstrated decreased muscle damage in flaps perfused with HTK compared with the UW-MPS-perfused flaps at 1 week after replantation. Conclusions: Machine perfusion of myocutaneous flaps for 24 hours with subsequent replantation is feasible, but warrants further research. Perfusion with HTK solution seemed to result in better histological outcomes 7 days after reperfusion compared with UW-MPS.
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Hoang G, Nguyen K, Le A. Metabolic Intersection of Cancer and Cardiovascular Diseases: Opportunities for Cancer Therapy. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1311:249-263. [PMID: 34014548 PMCID: PMC9703259 DOI: 10.1007/978-3-030-65768-0_18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
According to data from the World Health Organization, cardiovascular diseases and cancer are the two leading causes of mortality in the world [1]. Despite the immense effort to study these diseases and the constant innovation in treatment modalities, the number of deaths associated with cardiovascular diseases and cancer is predicted to increase in the coming decades [1]. From 2008 to 2030, due to population growth and population aging in many parts of the world, the number of deaths caused by cancer globally is projected to increase by 45%, corresponding to an annual increase of around four million people [1]. For cardiovascular diseases, this number is six million people [1]. In the United States, treatments for these two diseases are among the most costly and result in a disproportionate impact on low- and middleincome people. As the fight against these fatal diseases continues, it is crucial that we continue our investigation and broaden our understanding of cancer and cardiovascular diseases to innovate our prognostic and treatment approaches. Even though cardiovascular diseases and cancer are usually studied independently [2-12], there are some striking overlaps between their metabolic behaviors and therapeutic targets, suggesting the potential application of cardiovascular disease treatments for cancer therapy. More specifically, both cancer and many cardiovascular diseases have an upregulated glutaminolysis pathway, resulting in low glutamine and high glutamate circulating levels. Similar treatment modalities, such as glutaminase (GLS) inhibition and glutamine supplementation, have been identified to target glutamine metabolism in both cancer and some cardiovascular diseases. Studies have also found similarities in lipid metabolism, specifically fatty acid oxidation (FAO) and synthesis. Pharmacological inhibition of FAO and fatty acid synthesis have proven effective against many cancer types as well as specific cardiovascular conditions. Many of these treatments have been tested in clinical trials, and some have been medically prescribed to patients to treat certain diseases, such as angina pectoris [13, 14]. Other metabolic pathways, such as tryptophan catabolism and pyruvate metabolism, were also dysregulated in both diseases, making them promising treatment targets. Understanding the overlapping traits exhibited by both cancer metabolism and cardiovascular disease metabolism can give us a more holistic view of how important metabolic dysregulation is in the progression of diseases. Using established links between these illnesses, researchers can take advantage of the discoveries from one field and potentially apply them to the other. In this chapter, we highlight some promising therapeutic discoveries that can support our fight against cancer, based on common metabolic traits displayed in both cancer and cardiovascular diseases.
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Affiliation(s)
- Giang Hoang
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Department of Biomedical Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, USA
| | - Kiet Nguyen
- Department of Chemistry and Biology, Emory University, Atlanta, GA, USA
| | - Anne Le
- Department of Pathology and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, USA.
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Mei S, Song X, Wang Y, Wang J, Su S, Zhu J, Geng Y. Studies on Protection of Astaxanthin from Oxidative Damage Induced by H 2O 2 in RAW 264.7 Cells Based on 1H NMR Metabolomics. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:13568-13576. [PMID: 31709793 DOI: 10.1021/acs.jafc.9b04587] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Astaxanthin (AST) is a fat-soluble and non-vitamin A source of carotenoid that can quench reactive oxygen species and it has strong antioxidant and anti-inflammatory abilities. Herein, we have used H2O2 to establish a model of oxidative damage to RAW 264.7 cells and cells treated with vitamin C as the positive control group. The changes in metabolome were examined using 1H NMR and the results demonstrated that H2O2 treatment and various metabolic pathways such as amino acid, glucose, and glycerolipid metabolism were downregulated, which in turn affected citric acid cycle and energy status. AST could reverse downregulation of some of these metabolic pathways to a certain extent, and reduce cellular oxidative stress and death. The AST group differed from the vitamin C group in regulating d-glutamine, d-glutamic acid, pyruvate, and glycerolipid metabolism. The experimental results help to further understand the antioxidant effects of AST.
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Affiliation(s)
- Suhuan Mei
- Key Laboratory of Food Nutrition and Safety of SDNU, Provincial Key Laboratory of Animal Resistant Biology, College of Life Science , Shandong Normal University , Jinan 250014 , China
| | - Xiao Song
- Key Laboratory of Food Nutrition and Safety of SDNU, Provincial Key Laboratory of Animal Resistant Biology, College of Life Science , Shandong Normal University , Jinan 250014 , China
| | - Yali Wang
- Key Laboratory of Food Nutrition and Safety of SDNU, Provincial Key Laboratory of Animal Resistant Biology, College of Life Science , Shandong Normal University , Jinan 250014 , China
| | - Jun Wang
- Shandong Institute for Food and Drug Control , Jinan 250101 , China
| | - Shufang Su
- Shandong Institute for Food and Drug Control , Jinan 250101 , China
| | - Jianhua Zhu
- Shandong Institute for Food and Drug Control , Jinan 250101 , China
| | - Yue Geng
- Key Laboratory of Food Nutrition and Safety of SDNU, Provincial Key Laboratory of Animal Resistant Biology, College of Life Science , Shandong Normal University , Jinan 250014 , China
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Durante W. The Emerging Role of l-Glutamine in Cardiovascular Health and Disease. Nutrients 2019; 11:nu11092092. [PMID: 31487814 PMCID: PMC6769761 DOI: 10.3390/nu11092092] [Citation(s) in RCA: 100] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 08/29/2019] [Accepted: 08/30/2019] [Indexed: 12/29/2022] Open
Abstract
Emerging evidence indicates that l-glutamine (Gln) plays a fundamental role in cardiovascular physiology and pathology. By serving as a substrate for the synthesis of DNA, ATP, proteins, and lipids, Gln drives critical processes in vascular cells, including proliferation, migration, apoptosis, senescence, and extracellular matrix deposition. Furthermore, Gln exerts potent antioxidant and anti-inflammatory effects in the circulation by inducing the expression of heme oxygenase-1, heat shock proteins, and glutathione. Gln also promotes cardiovascular health by serving as an l-arginine precursor to optimize nitric oxide synthesis. Importantly, Gln mitigates numerous risk factors for cardiovascular disease, such as hypertension, hyperlipidemia, glucose intolerance, obesity, and diabetes. Many studies demonstrate that Gln supplementation protects against cardiometabolic disease, ischemia-reperfusion injury, sickle cell disease, cardiac injury by inimical stimuli, and may be beneficial in patients with heart failure. However, excessive shunting of Gln to the Krebs cycle can precipitate aberrant angiogenic responses and the development of pulmonary arterial hypertension. In these instances, therapeutic targeting of the enzymes involved in glutaminolysis such as glutaminase-1, Gln synthetase, glutamate dehydrogenase, and amino acid transaminase has shown promise in preclinical models. Future translation studies employing Gln delivery approaches and/or glutaminolysis inhibitors will determine the success of targeting Gln in cardiovascular disease.
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Affiliation(s)
- William Durante
- Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212, USA.
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Yeşil H, Tuğlu I. The relation of oxidative stress and apoptosis to histopathologic alterations in the lungs as a result of global cerebral ischemia. Biotech Histochem 2019; 94:555-568. [PMID: 31373845 DOI: 10.1080/10520295.2019.1601768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
Abstract
Heart attack and oxygen deficiency may cause necrosis in the brain and other tissues. We investigated the histopathological effects of nitric oxide (NO) on ischemia/reperfusion in lung and hippocampus using a rat brain bilateral occlusion ischemia model. Male rats were assigned to sham (SH), ischemic preconditioning (PC), global ischemia (GI) and ischemic reperfusion (IR) groups. Before ischemia was induced, blood was drawn to induce hypovolemic hypotension and for blood gas testing. After sacrifice, samples of hippocampus were harvested. Sections were examined using hematoxylin and eosin (H & E) staining and immunostaining using primary antibodies for GFAP, S100β, iNOS, eNOS and the TUNEL method. Following ischemia, we found evidence of gliosis induced oxidative stress and apoptosis in the hippocampus. No significant differences were detected between the SH and PC groups. In the GI and IR groups, apoptosis and necrosis were observed in the hippocampus. Lung sections were stained with H & E and Masson's trichrome (MT) and immunostained for iNOS and eNOS. The TUNEL method was used to detect apoptosis. Interstitial edema, vascular congestion, intra-alveolar hemorrhage, perivascular edema, neutrophil infiltration and disruption of alveoli were observed after global ischemia and ischemic reperfusion. Inflammatory cells were detected in the connective tissue. The IR and GI groups exhibited significantly more apoptotic cells than the SH or PC groups. Free radicals, such as nitric oxide (NO), that appear following ischemia and reperfusion in the brain may also injure the lungs. Increased NO in both lung and brain tissue suggests that apoptosis in these organs can be induced by reactive nitrogen species.
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Affiliation(s)
- H Yeşil
- Departments of Midwifery, Celal Bayar University Manisa, Manisa, Turkey
| | - I Tuğlu
- Histology and Embryology, Faculty of Medicine, Celal Bayar University Manisa, Manisa, Turkey
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Effects of Glutathione on Mechanical Allodynia and Central Sensitization in Chronic Postischemic Pain Rats. Pain Res Manag 2017; 2017:7394626. [PMID: 29209138 PMCID: PMC5676478 DOI: 10.1155/2017/7394626] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Revised: 09/08/2017] [Accepted: 09/18/2017] [Indexed: 01/08/2023]
Abstract
Background The chronic postischemia pain (CPIP) model is an animal model using ischemia/reperfusion injury that mimics the symptoms of complex regional pain syndrome type I. Glutathione (GSH) prevents ischemia/reperfusion injury by scavenging free radicals. We conducted this study to investigate the protective effect of GSH in CPIP rats via changes of mechanical allodynia and phospholyration of the N-methyl-D-aspartate receptor subunit GluN1. Methods We divided 45 rats into 5 groups: sham, CPIP, CPIP + GSH 100 mg/kg, CPIP + GSH 200 mg/kg, and CPIP + GSH 500 mg/kg. Rats in the sham and CPIP groups received normal saline and rats in the other groups received GSH at the designated doses thirty minutes prior to reperfusion. Withdrawal thresholds were evaluated before sugery as well as 1, 3, and 7 days after surgery. pGluN1 level in the spinal cord was also measured. Results GSH treated rats show a significant increase in the withdrawal thresholds of both hind paws as compared with the CPIP group dose-dependently. The expression of pGluN1 in the GSH treated rats significantly decreased as compared to the CPIP group (all P < 0.05). Conclusion These findings suggest that GSH inhibited the development of mechanical allodynia and central sensitization in CPIP rats.
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Avila JG, Tsujimura T, Oberholzer J, Churchill T, Salehi P, Shapiro AMJ, Lakey JRT. Improvement of Pancreatic Islet Isolation Outcomes Using Glutamine Perfusion during Isolation Procedure. Cell Transplant 2017; 12:877-881. [DOI: 10.3727/000000003771000228] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
During procurement, isolation, and transplantation, islets are exposed to high levels of oxidative stress triggering a variety of signaling pathways that can ultimately lead to cell death. Glutamine is an important cellular fuel and an essential precursor for the antioxidant glutathione. The aim of this study was to examine the role of intraductal glutamine administration in facilitating recovery of isolated rat islets from pancreases subjected to a clinically relevant period of warm ischemia. Islets were isolated in Sprague-Dawley (SD) rats (n= 18 per group). Pancreata in groups 1 and 2 were procured immediately while groups 3 and 4 were subjected to 30-min warm ischemia. Groups 2 and 4 were treated intraductally with 5 mM glutamine prior to pancreatectomy. Exposure to 30-min warm ischemia significantly reduced islet yield [groups 1 & 2 (nonischemia): 503 ± 29 islets/rat vs. groups 3 & 4 (ischemia): 247 ± 26 islets/rat; p < 0.05]. Intraductal glutamine treatment significantly improved islet yield when pancreata were subjected to 30-min warm ischemia [144 ± 16 islets/rat without glutamine (group 3) vs. 343 ± 36 islets/rat with glutamine (group 4), p < 0.05]. Glutamine also significantly improved islet viability (values were 50 ± 4% in group 4 vs. 27 ± 3% in group 3, p < 0.05). Similarly, glutathione (reduced) levels were significantly elevated in both glutamine-treated groups; however, this increase was greatest in tissues exposed to ischemia (2.76 ± 0.04 nmol/mg protein in group 4 vs. 1.66 ± 0.04 nmol/mg protein in group 3, p < 0.05). Intraductal glutamine administration considerably improves the islet yield, viability, and augments endogenous glutathione levels in pancreata procured after a clinically relevant period of ischemia. Intraductal administration of glutamine at the time of digestive enzyme delivery into the harvested pancreas may represent a simple yet effective tool to improve islet yields in clinical isolations.
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Affiliation(s)
- J. G. Avila
- Surgical-Medical Research Institute, University of Alberta, 1074 Dentistry/Pharmacy Centre, Edmonton, Canada T6G 2N8
- Department of Surgery, University of Alberta, 1074 Dentistry/Pharmacy Centre, Edmonton, Canada T6G 2N8
| | - T. Tsujimura
- Surgical-Medical Research Institute, University of Alberta, 1074 Dentistry/Pharmacy Centre, Edmonton, Canada T6G 2N8
- Department of Surgery, University of Alberta, 1074 Dentistry/Pharmacy Centre, Edmonton, Canada T6G 2N8
| | - J. Oberholzer
- Department of Surgery, University of Alberta, 1074 Dentistry/Pharmacy Centre, Edmonton, Canada T6G 2N8
| | - T. Churchill
- Surgical-Medical Research Institute, University of Alberta, 1074 Dentistry/Pharmacy Centre, Edmonton, Canada T6G 2N8
| | - P. Salehi
- Surgical-Medical Research Institute, University of Alberta, 1074 Dentistry/Pharmacy Centre, Edmonton, Canada T6G 2N8
| | - A. M. James Shapiro
- Surgical-Medical Research Institute, University of Alberta, 1074 Dentistry/Pharmacy Centre, Edmonton, Canada T6G 2N8
- Department of Surgery, University of Alberta, 1074 Dentistry/Pharmacy Centre, Edmonton, Canada T6G 2N8
| | - J. R. T. Lakey
- Surgical-Medical Research Institute, University of Alberta, 1074 Dentistry/Pharmacy Centre, Edmonton, Canada T6G 2N8
- Department of Surgery, University of Alberta, 1074 Dentistry/Pharmacy Centre, Edmonton, Canada T6G 2N8
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Gürsul C, Ekinci Akdemir FN, Akkoyun T, Can İ, Gül M, Gülçin İ. Protective effect of Naringin on experimental hindlimb ischemia/reperfusion injury in rats. J Enzyme Inhib Med Chem 2016; 31:56-61. [DOI: 10.3109/14756366.2016.1167050] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Cebrail Gürsul
- Department of Physiology, Faculty of Medicine, Erzincan University, Erzincan, Turkey,
| | | | - Turan Akkoyun
- Department of Physiology, Faculty of Veterinary, Siirt University, Siirt, Turkey,
| | - İsmail Can
- Department of Histology, Faculty of Medicine, Kafkas University, Kars, Turkey,
| | - Mustafa Gül
- Department of Physiology, Faculty of Medicine, Atatürk University, Erzurum, Turkey,
| | - İlhami Gülçin
- Department of Chemistry, Faculty of Sciences, Atatürk University, Erzurum, Turkey, and
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
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Shih YM, Shih JM, Pai MH, Hou YC, Yeh CL, Yeh SL. Glutamine Administration After Sublethal Lower Limb Ischemia Reduces Inflammatory Reaction and Offers Organ Protection in Ischemia/Reperfusion Injury. JPEN J Parenter Enteral Nutr 2015; 40:1122-1130. [PMID: 26059902 DOI: 10.1177/0148607115587949] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2015] [Accepted: 04/27/2015] [Indexed: 11/16/2022]
Abstract
BACKGROUND This study investigated the effects of intravenous glutamine (GLN) administration on the expression of adhesion molecules and inflammatory mediators in a mice model of hind limb ischemia/reperfusion (IR) injury. METHODS There were 3 IR groups and 1 normal control (NC) group. The NC group did not undergo the IR procedure. Mice in the IR groups underwent 90 minutes of limb ischemia followed by a variable period of reperfusion. Ischemia was performed by applying a 4.5-oz orthodontic rubber band to the left thigh. Mice in one IR group were sacrificed immediately after reperfusion. The other 2 IR groups were injected once with either 0.75 g GLN/kg body weight (G group) or an equal volume of saline (S group) via tail vein before reperfusion. Mice in the S and G groups were subdivided and sacrificed at 4 or 24 hours after reperfusion. RESULTS IR enhanced the inflammatory cytokine gene expressions in muscle. Also, plasma interleukin (IL)-6 levels, blood neutrophil percentage, and the adhesion molecule and chemokine receptors expressed by leukocytes were upregulated after reperfusion. The IR-induced muscle inflammatory mediator gene expressions, blood macrophage percentage, and plasma IL-6 concentration had declined at an early or a late phase of reperfusion when GLN was administered. Histologic findings also found that remote lung injury was attenuated during IR insult. CONCLUSIONS A single dose of GLN administration immediately after sublethal lower limb ischemia reduces the inflammatory reaction locally and systemically; this may offer local and distant organ protection in hind limb IR injury.
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Affiliation(s)
- Yao-Ming Shih
- School of Nutrition and Health Sciences, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.,Department of Surgery, Cathay General Hospital, Taipei, Taiwan
| | - Juey-Ming Shih
- School of Nutrition and Health Sciences, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.,Department of Surgery, Cathay General Hospital, Taipei, Taiwan
| | - Man-Hui Pai
- Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yu-Chen Hou
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Chiu-Li Yeh
- Department of Nutrition and Health Sciences, Chinese Culture University, Taipei, Taiwan
| | - Sung-Ling Yeh
- School of Nutrition and Health Sciences, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan
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Valparaiso AP, Vicente DA, Bograd BA, Elster EA, Davis TA. Modeling acute traumatic injury. J Surg Res 2014; 194:220-32. [PMID: 25481528 DOI: 10.1016/j.jss.2014.10.025] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2014] [Revised: 10/16/2014] [Accepted: 10/17/2014] [Indexed: 11/26/2022]
Abstract
Acute traumatic injury is a complex disease that has remained a leading cause of death, which affects all ages in our society. Direct mechanical insult to tissues may result in physiological and immunologic disturbances brought about by blood loss, coagulopathy, as well as ischemia and reperfusion insults. This inappropriate response leads to an abnormal release of endogenous mediators of inflammation that synergistically contribute to the incidence of morbidity and mortality. This aberrant activation and suppression of the immune system follows a bimodal pattern, wherein activation of the innate immune responses is followed by an anti-inflammatory response with suppression of the adaptive immunity, which can subsequently lead secondary insults and multiple organ dysfunction. Traumatic injury rodent and swine models have been used to describe many of the underlying pathologic mechanisms, which have led to an improved understanding of the morbidity and mortality associated with critically ill trauma patients. The enigmatic immunopathology of the human immunologic response after severe trauma, however, has never more been apparent and there grows a need for a clinically relevant animal model, which mimics this immune physiology to enhance the care of the most severely injured. This has necessitated preclinical studies in a more closely related model system, the nonhuman primate. In this review article, we summarize animal models of trauma that have provided insight into the clinical response and understanding of cellular mechanisms involved in the onset and progression of ischemia-reperfusion injury as well as describe future treatment options using immunomodulation-based strategies.
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Affiliation(s)
- Apple P Valparaiso
- Department of Regenerative Medicine, Naval Medical Research Center, Silver Spring, Maryland; Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland
| | - Diego A Vicente
- Department of Regenerative Medicine, Naval Medical Research Center, Silver Spring, Maryland; Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland; Department of Surgery, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Benjamin A Bograd
- Department of Regenerative Medicine, Naval Medical Research Center, Silver Spring, Maryland; Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland; Department of Surgery, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Eric A Elster
- Department of Regenerative Medicine, Naval Medical Research Center, Silver Spring, Maryland; Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland; Department of Surgery, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Thomas A Davis
- Department of Regenerative Medicine, Naval Medical Research Center, Silver Spring, Maryland; Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
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Iltar S, Kılınç CY, Alemdaroğlu KB, Ozcan S, Aydoğan NH, Sürer H, Kılınç AŞ. Does the method of expression of venous blood affect ischaemia/reperfusion damage in tourniquet use? An experimental study on rabbits. Injury 2013; 44:1493-7. [PMID: 23481315 DOI: 10.1016/j.injury.2013.02.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2012] [Revised: 02/02/2013] [Accepted: 02/06/2013] [Indexed: 02/02/2023]
Abstract
The aim of this study was to compare the ischaemia and reperfusion phases of two tourniquet application models (Group 1: expressing the blood by a sterile rubber bandage and Group 2: elevation of the limb for several minutes) using an analysis of ischaemia/reperfusion parameters and blood pH. Sixteen New Zealand rabbits were used. Muscle samples were extracted from the triceps surae; at phase A (baseline: just before tourniquet application), phase B (ischaemia: 3h after tourniquet inflation) and phase C (2h after tourniquet deflation). Nitrite, nitrate, reduced glutathione, myeloperoxidase, malondyaldehyde were measured in the samples. Blood pH was also measured at each phase. Group 2 had significantly decreased nitrite (p=0.007) and nitrate (p=0.01) levels compared to Group 1 while passing from phase A to phase B. The pH decrease through the phases was significant within Group 1 (p=0.006) and was not significant within Group 2 (p=0.052). Lower levels of NO metabolites nitrate and nitrite, result from tourniquet use with incomplete venous blood expression by elevation. Also, with this technique severe acidosis is less likely to occur than when a tourniquet is used with expression of the venous blood by rubber bandage. These findings may help in the decision of which tourniquet technique is to be used for potentially long operations which may exceed 2h.
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Affiliation(s)
- Serkan Iltar
- Ankara Training and Research Hospital, Department of Orthopaedics and Traumatology, Turkey
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Chamney C, Godar M, Garrigan E, Huey KA. Effects of glutamine supplementation on muscle function and stress responses in a mouse model of spinal cord injury. Exp Physiol 2012; 98:796-806. [PMID: 23143993 DOI: 10.1113/expphysiol.2012.069658] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Spinal cord injury (SCI) results in loss of muscle function due to rapid breakdown of contractile proteins. Glutamine supplementation improves clinical outcomes, but its effects on muscle function after SCI are unknown. The benefits of glutamine in non-skeletal muscle tissues involve elevated heat shock protein (Hsp)70 and Hsp25, but the muscle response may differ because it is the largest contributor to plasma glutamine. We tested the hypothesis that glutamine preserves muscle function after SCI and that this is associated with increased heat shock protein and reduced inflammatory factors, interleukin-6 (IL-6) and tumour necrosis factor-α (TNFα). Changes in plantarflexor force, fatigability and total myofibrillar, Hsp70, Hsp25, IL-6 and TNFα muscle protein levels were measured 7 days after sham or spinal cord transection surgery in mice receiving daily placebo or glutamine. Compared with placebo, after SCI glutamine significantly attenuated the reductions in maximal isometric force (0.22 ± 0.01 versus 0.31 ± 0.03 N, respectively) and fatigue resistance (34 ± 4 versus 59 ± 4% of initial force, respectively). Glutamine significantly ameliorated the loss of myofibrillar protein with spinal cord transection. Spinal cord transection was associated with decreased Hsp70 and Hsp25 with glutamine only (45 ± 3 and 44 ± 5% of placebo, respectively). Glutamine significantly reduced spinal cord transection-associated increases in IL-6 and TNFα compared with placebo (38 ± 6 and 37 ± 8% of placebo, respectively). Functionally, early reductions in contractile protein, force and fatigue resistance after SCI were reversed with glutamine. Spinal cord transection-associated reductions in Hsp70, Hsp25, IL-6 and TNFα with glutamine versus placebo suggest lower stress in the muscle, possibly related to a reduced need to produce glutamine. These findings support glutamine as a therapeutic intervention to accelerate recovery of muscle function after SCI.
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Affiliation(s)
- Carissa Chamney
- College of Pharmacy and Health Sciences, Drake University, 2507 University Avenue, Des Moines, IA 50311, USA
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Itoh M, Shimokawa N, Tajika Y, Murakami T, Aotsuka N, Lesmana R, Farenia R, Iwasaki T, Okda J, Yorifuji H, Koibuchi N. Alterations of biochemical marker levels and myonuclear numbers in rat skeletal muscle after ischemia-reperfusion. Mol Cell Biochem 2012; 373:11-8. [PMID: 23065010 DOI: 10.1007/s11010-012-1470-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2012] [Accepted: 09/26/2012] [Indexed: 11/28/2022]
Abstract
Prolonged ischemia-reperfusion results in various damages in skeletal muscle. Following reperfusion, although the damaged muscles undergo regeneration, the precise process and mechanism of regeneration have not yet been fully understood. Here, we show the altered levels of plasma biochemical markers of muscle damage, and the change in myonuclear numbers in adult rat skeletal muscle by ischemia-reperfusion. Male Wistar rats were subjected to unilateral hindlimb ischemia by clamping the anterior tibial artery for 2 h before reperfusion. Both plasma creatine kinase activity and C-reactive protein levels in plasma were increased significantly at 0.5 h of reperfusion and returned to the control level at 24 h. The transverse sectional area of muscle belly of the anterior tibial muscles in ischemic side was significantly decreased by 20 % compared with those in sham-ischemic (control) side at 2 days, and returned to the control level at 5 days of reperfusion. Moreover, the number of interstitial nuclei in the ischemic side were significantly increased at 5-14 days and returned to the control level at 21 days of reperfusion. Central nuclei that are specifically observed in regenerating muscle, appeared at 5 days, reached a peak at 14 days, and disappeared at 28 days of reperfusion. Furthermore, MyoD, a regulatory factor for myogenesis, showed a transient expression at 5 days of reperfusion. These results indicate that, although the size of muscle seems to be recovered by 5 days of reperfusion, the most active muscle regeneration occurs much later, as shown by the increase in central nuclei.
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Affiliation(s)
- Motoharu Itoh
- Department of Integrative Physiology, Gunma University Graduate School of Medicine, 3-39-22, Maebashi, Gunma 371-8511, Japan
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Abstract
OBJECTIVES Ischemia-reperfusion (I/R) injury can have detrimental effects on skeletal muscle. We have shown that vessel permeability can be minimized in a hypothermic setting and also by administering the nitric oxide synthase (NOS) stimulator, L-arginine, at physiologic temperatures. The purpose of this study was to examine and compare skeletal muscle contractility after an I/R insult during hypothermic conditions, warm conditions, and also with the administration of L-arginine at physiologic temperatures. We hypothesized that hypothermia and L-arginine administration will also demonstrate protective effects to skeletal muscle contractility. METHODS Using Sprague-Dawley rats, the extensor digitorum longus muscle was rotated on its vascular pedicle to a thermo-controlled stage. Ischemia was established using an atraumatic femoral artery tourniquet. Reperfusion was performed under control and experimental conditions including local hypothermia and intravenous L-arginine. After harvesting experimental muscles, contractility was then quantified by using a tissue bath stimulator with force transducers. RESULTS Warm reperfusion resulted in marked decrease in muscle contractility compared with sham animals. Local hypothermia showed statistically significant preservation of contractility compared with the sham group. This protective effect was recapitulated by the application of NOS inducers (L-arginine) at warm conditions. CONCLUSIONS These findings demonstrate that hypothermia and L-arginine are protective of skeletal muscle contractility after an I/R injury. The results presented may have profound effects on future therapeutic recommendations and suggest possible pathways for clinical intervention to modulate I/R injury, which is commonplace in orthopaedic trauma and reconstructive surgery.
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H S Kumar S, Anandan R. Biochemical studies on the cardioprotective effect of glutamine on tissue antioxidant defense system in isoprenaline-induced myocardial infarction in rats. J Clin Biochem Nutr 2011; 40:49-55. [PMID: 18437213 PMCID: PMC2291504 DOI: 10.3164/jcbn.40.49] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2006] [Accepted: 08/07/2006] [Indexed: 11/22/2022] Open
Abstract
Oxidative stress is one of the mechanisms with a central role involved in the pathogenesis of myocardial infarction. The protective effect of glutamine on myocardial antioxidant defense system was investigated during isoprenaline-induced myocardial infarction, an animal model of myocardial infarction of human beings. Levels of diagnostic marker enzymes in plasma, reduced glutathione (GSH) and lipid peroxides and the activities of glutathione peroxidase, glutathione-S-transferase, catalase and superoxide dismutase in heart tissue were determined. Injection of isoprenaline caused significant increases in the levels of diagnostic marker enzymes in plasma and lipid peroxidation in heart tissue. A parallel decline in the levels of ATP (Adenosine triphosphate) and GSH and the activities of glutathione-dependent antioxidant enzymes and antiperoxidative enzymes in heart tissue was also observed. Prior oral administration of glutamine significantly prevented isoprenaline-induced adverse effects and maintained myocardial antioxidant status at near normal status. The cardioprotective effect of glutamine is probably related to a strengthening of the myocardial membrane by its membrane stabilizing action, or to a counteraction of free radicals by its antioxidant property, or to its ability to maintain near to normal status the activities of free radical scavenging enzymes and the level of GSH, which protect myocardial membrane against oxidative damage by decreasing lipid peroxidation.
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Affiliation(s)
- Subramaniam H S Kumar
- Department of Biotechnology, Institute of Science and Technology, Jawaharlal Nehru Technological University, Kukatpally, Hyderabad-500 072, INDIA
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Taher MA, Nassir ES. Beneficial effects of clopidogrel on glycemic indices and oxidative stress in patients with type 2 diabetes. Saudi Pharm J 2011; 19:107-13. [PMID: 23960748 PMCID: PMC3745185 DOI: 10.1016/j.jsps.2011.01.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2010] [Accepted: 01/07/2011] [Indexed: 12/14/2022] Open
Abstract
Objective of present study is to evaluate the possible role of clopidogrel in improving glycemic indices and oxidative stress in patients with type 2 diabetes. This study was performed on 42 uncontrolled type 2 diabetic patients at the specialized center for Endocrinology and Diabetes, Al-Rasafa Directorate of Health, Baghdad. All of the patients were treated with (glibenclamide 5 mg at morning) and randomized into two groups: the first group includes 22 patients treated with clopidogrel tablets (75 mg/day) for 2 months; the second group includes 20 patients treated with a placebo formula (sodium bicarbonate 200 mg/day) for the same period. Treatment with clopidogrel produced significant improvement (P < 0.05) in fasting serum glucose (FSG), fasting serum insulin level, quantitative insulin sensitivity check index (QUICKI); and oxidative stress markers: serum malondialdehyde (MDA) and serum reduced glutathione (GSH) compared to their baseline levels. There was significant elevation (P < 0.05) in both FSG and fasting serum insulin and the MDA level with significant reduction (P < 0.05) in QUICKI of placebo group compared to their baseline levels. However, clopidogrel produced significant elevation (P < 0.05) in AST and ALT levels but placebo formula caused no significant alteration (P > 0.05) in the serum levels of these two enzymes. In conclusion the treatment with clopidogrel improved glycemic indices and reduced oxidative stress in patients with type 2 diabetes.
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Affiliation(s)
- Mohammed A. Taher
- Department of Clinical Laboratory Sciences, College of Pharmacy, University of Baghdad, Baghdad, Iraq
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Stangl R, Szijártó A, Ónody P, Tamás J, Tátrai M, Hegedűs V, Blázovics A, Lotz G, Kiss A, Módis K, Gerő D, Szabó C, Kupcsulik P, Harsányi L. Reduction of Liver Ischemia-Reperfusion Injury Via Glutamine Pretreatment. J Surg Res 2011; 166:95-103. [DOI: 10.1016/j.jss.2009.09.047] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2009] [Revised: 09/13/2009] [Accepted: 09/30/2009] [Indexed: 01/28/2023]
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Mondello S, Galuppo M, Mazzon E, Italiano D, Mondello P, Aloisi C, Cuzzocrea S. Glutamine treatment attenuates the development of organ injury induced by zymosan administration in mice. Eur J Pharmacol 2011; 658:28-40. [PMID: 21349270 DOI: 10.1016/j.ejphar.2011.02.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2010] [Revised: 12/16/2010] [Accepted: 02/05/2011] [Indexed: 01/10/2023]
Abstract
Glutamine is the most abundant amino acid in the bloodstream. It is important in nucleotide synthesis, is anti-catabolic, has anti-oxidant properties via metabolism to glutathione, may enhance immune responsiveness and possesses immunoregulatory functions. Moreover, it reduces atrophy of intestinal mucosa in animals on total parenteral nutrition and prevents intestinal mucosal injury accompanying small bowel transplantation, chemotherapy and radiation. In the present study, we investigated the effects of glutamine on development of non-septic shock caused by zymosan. Mice received either zymosan (500 mg/kg, administered i.p., as a suspension in saline) or vehicle (saline). Glutamine (1.5 mg/kg i.p.) was administered 1 and 6h after zymosan administration. Organ failure and systemic inflammation in mice were assessed 18 h after administration of zymosan and/or glutamine. Glutamine-treatment reduced the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan-injection and also attenuated the pancreatic and gut injury. Inflammatory and apoptotic parameters were evaluated to better investigate the effects of the glutamine-administration. So, by immunohistochemical analysis and in vitro assays, we have clearly showed that glutamine reduces: 1) the histological damage in pancreas and gut; 2) the inducible nitric oxide synthase expression; 3) nitrotyrosine and poly (ADP-ribose) formation; 4) TNF-α and IL-1β tissue and plasma levels; 5) FasL localization; and 6) alteration of the balance between Bax and Bcl-2. In addition, at the end of the observation period (7 days), zymosan causes severe illness in the mice characterized by a systemic toxicity, significant loss of body weight and mortality. Glutamine-treatment significantly reduced all these parameters.
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Araújo Júnior RJC, Silva Júnior RGD, Vasconcelos MPPD, Guimarães SB, Vasconcelos PRLD, Garcia JHP. Preconditioning with L-alanyl-glutamine reduces hepatic ischemia-reperfusion injury in rats. Acta Cir Bras 2011; 26 Suppl 1:8-13. [DOI: 10.1590/s0102-86502011000700003] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
PURPOSE: To evaluate the effects of pre-conditioning with L-alanyl- glutamine (L-Ala-Gln) in rats subjected to total hepatic ischemia. METHODS: Thirty Wistar rats, average weight 300g, were randomly assigned to 3 groups (n=10): G-1 - Saline, G-2- L-Ala-Gln, G-3-control (Sham). G-1 and G-3 groups were treated with saline 2.0 ml or L-Ala-Gln (0.75mg/Kg) intraperitoneally (ip) respectively, 2 hours before laparotomy. Anesthetized rats were subjected to laparotomy and total hepatic ischemia (30 minutes) induced by by clamping of portal triad. Control group underwent peritoneal puncture, two hours before the sham operation (laparotomy only). At the end of ischemia (G1 and G2), the liver was reperfused for 60 minutes. Following reperfusion blood samples were collected for evaluation of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels. Liver (medium lobe) was removed for immunohistochemistry study with antibody for Caspase-3. RESULTS: It was found a significant decrease (p<0.05) of ALT levels (270.6 +40.8 vs 83.3 +5.5 - p <0.05), LDH (2079.0 +262.4 vs. 206.6 +16.2 - p <0.05) and Caspase-3 expression (6.72 +1.35 vs. 2.19 +1.14, p <0.05) in rats subjected to I / R, comparing the group treated with L-Ala -Gln with G-2. Also, the ALT level was significantly lower (P<0.05) in G-1 and G-2 groups than in G-3 (control group). CONCLUSION: L-Ala-Gln preconditioning in rats submitted to hepatic I/R significantly reduces ALT, LDH and Caspase-3 expression, suggesting hepatic protection.
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Koca K, Yurttas Y, Bilgic S, Cayci T, Topal T, Durusu M, Kaldirim U, Akgul EO, Ozkan H, Yanmis I, Oguz E, Tunay S, Korkmaz A, Basbozkurt M. Effect of preconditioned hyperbaric oxygen and ozone on ischemia-reperfusion induced tourniquet in skeletal bone of rats. J Surg Res 2010; 164:e83-9. [PMID: 20850777 DOI: 10.1016/j.jss.2010.06.030] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2010] [Revised: 05/29/2010] [Accepted: 06/28/2010] [Indexed: 11/15/2022]
Abstract
BACKGROUND The aim of the study was to investigate effect of I/R injury on bone tissue and protective role of hyperbaric oxygen precondition (HBO-PC) and ozone precondition (O(3)-PC) on I/R injury by using biochemical analysis. MATERIALS AND METHODS Thirty-two rats were included in study. The animals were divided into four equal groups: sham operation, I/R, I/R+HBO and I/R+O(3). One session of 60 min, 3 ATA, 3-4 L/min, 100% oxygenation was defined as one dose of HBO. First dose of HBO was administrated 72 h before ischemia. Subsequent, one-dose of HBO administrated per 12 hours until ischemia time (total seven doses); 0.7 mg/kg ozone/oxygen mixture intraperitoneally was defined as one dose of ozone. First dose of O(3) was administered 72 h before ischemia (total four doses). I/R model was induced in anesthetized rats by unilateral (right) femoral artery clipping for 2 h followed by 22 h of reperfusion. The right tibia and were harvested. Tissue was assayed for levels of malondialdehyde (MDA) and protein carbonyl (PCO), activities of superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). RESULTS MDA and PCO levels were increased in I/R group. SOD activity was increased; GSH-Px activity was decreased in I/R group. MDA and PCO levels were decreased, SOD and GSH-Px activities were increased in both HBO+I/R and O(3)+I/R groups. CONCLUSION It has been shown that levels of MDA and PCO in bone were increased followed by 2 h of ischemia and 22 h of reperfusion period. Ozone-PC and HBO-PC has protective effect against skeletal bone I/R injury by decreasing levels of MDA and PCO, increasing activities of SOD and GSH-Px in rats.
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Affiliation(s)
- Kenan Koca
- Department of Orthopaedic Surgery, Gulhane Military Medical Academy, Etlik-Ankara, Turkey.
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l-Alanyl-Glutamine Preoperative Infusion in Patients with Critical Limb Ischemia Subjected to Distal Revascularization Reduces Tissue Damage and Protects from Oxidative Stress. Ann Vasc Surg 2010; 24:461-7. [DOI: 10.1016/j.avsg.2010.01.005] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2008] [Revised: 12/03/2009] [Accepted: 01/10/2010] [Indexed: 11/22/2022]
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Tzioupis C, Cox G, Giannoudis PV. Acute compartment syndrome of the lower extremity: an update. ACTA ACUST UNITED AC 2009. [DOI: 10.1016/j.mporth.2009.09.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Meador BM, Huey KA. Glutamine preserves skeletal muscle force during an inflammatory insult. Muscle Nerve 2009; 40:1000-7. [PMID: 19705479 DOI: 10.1002/mus.21430] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
The purpose of this study was to test the hypothesis that acute glutamine (GLN) supplementation can counteract skeletal muscle contractile dysfunction occurring in response to inflammation by elevating muscle heat shock protein (Hsp) expression and reducing inflammatory cytokines. Mice received 5 mg/kg lipopolysaccharide (LPS) concurrently with 1 g/kg GLN or vehicle treatments. Plantarflexor isometric force production was measured at 2 hours post-injection. Blood and gastrocnemius muscles were collected, and serum and muscle tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and muscle Hsp70 and Hsp25 were quantified. Saline/LPS treatment was associated with a 33% reduction in maximal force and elevated serum TNF-alpha and IL-6. GLN completely prevented this force decrement with LPS. GLN was found to reduce muscle Hsp70 and IL-6, but only in the presence of LPS. GLN supplementation provides an effective, novel, clinically applicable means of preserving muscle force during acute inflammation. These data indicate that force preservation is not dependent on reductions in serum cytokines or muscle TNF-alpha, or elevated Hsp levels.
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Affiliation(s)
- Benjamin M Meador
- Department of Kinesiology, University of Illinois at Urbana-Champaign, 120 Freer Hall, 906 South Goodwin Avenue, Urbana, Illinois 61801, USA.
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Ward R, Souder N, Stahl D, Hunter F, Probe R, Chaput C, Childs E. The role of nitric oxide synthase and heme oxygenase in the protective effect of hypothermia in ischemia-reperfusion injury. J Bone Joint Surg Am 2009; 91:2637-45. [PMID: 19884438 DOI: 10.2106/jbjs.h.01324] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Ischemia-reperfusion injury plays an important role in limb salvage following limb ischemia. The purpose of the present study was to evaluate the effect of local hypothermia and chemical modulators on microvascular permeability following ischemia-reperfusion injury in skeletal muscle. METHODS Sprague-Dawley rats were randomized into nine groups. Postcapillary venules of the extensor digitorum longus muscle were visualized with use of intravital microscopy. Following an intravenous bolus of fluorescein isothiocyanate-labeled albumin, the intravascular and extravascular space was examined for leak. Rats in the sham group underwent a one-hour mock ischemic period without the application of a femoral artery tourniquet, followed by one hour of mock reperfusion. The treatment groups (n = 5 in each group) had the tourniquet applied for one hour, followed by one hour of reperfusion at 10 degrees C (cold) alone, at 10 degrees C with nitric oxide synthase inhibitor, at 10 degrees C with heme oxygenase inhibitor, at 10 degrees C with a combination of inhibitors, at 34 degrees C (warm) alone, at 34 degrees C with a heme oxygenase inducer, at 34 degrees C with a nitric oxide synthase inducer, or at 34 degrees C with a combination of inducers. RESULTS Rats in the sham group did not show a significant increase in microvascular permeability. Rats in the warm ischemia/reperfusion group displayed significant increases in microvascular permeability, as did the rats that received inhibitors of heme oxygenase and nitric oxide synthase at 10 degrees C. No significant increase in microvascular permeability was observed in the animals in the cold ischemia/reperfusion group or in animals that received inducers of heme oxygenase and nitric oxide synthase at 34 degrees C. CONCLUSIONS Local hypothermia protects skeletal muscle from increased microvascular permeability following ischemia-reperfusion injury. This protective effect is also seen with the induction of the nitric oxide synthase and heme oxygenase systems at physiologic temperature. We also have shown that the protective effects of hypothermia are blocked by giving heme oxygenase and nitric oxide synthase inhibitors while keeping the muscle hypothermic. These findings demonstrate that heme oxygenase and nitric oxide synthase play a combined role in ischemia-reperfusion injury, suggesting possible pathways for clinical intervention to modulate injury seen following trauma, tourniquet use, vascular surgery, and microvascular surgery.
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Affiliation(s)
- Russell Ward
- Departments of Orthopaedic Surgery, Scott and White Memorial Hospital, 2401 South 31st Street, Temple, TX 76508, USA
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Schuster H, Blanc MC, Bonnefont-Rousselot D, Nakib S, Le Tourneau A, Fürst P, Cynober L, De Bandt JP. Protective effects of glutamine dipeptide and α-tocopherol against ischemia–reperfusion injury in the isolated rat liver. Clin Nutr 2009; 28:331-7. [DOI: 10.1016/j.clnu.2009.02.011] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2008] [Revised: 01/20/2009] [Accepted: 02/20/2009] [Indexed: 10/21/2022]
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Effect of hydroxyethyl starch 130/0.4 on ischaemia/reperfusion in rabbit skeletal muscle. Eur J Anaesthesiol 2009; 26:160-5. [DOI: 10.1097/eja.0b013e32831ac4a7] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Dexmedetomidine reduces the ischemia-reperfusion injury markers during upper extremity surgery with tourniquet. J Hand Surg Am 2008; 33:941-7. [PMID: 18656769 DOI: 10.1016/j.jhsa.2008.01.014] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2007] [Revised: 12/22/2007] [Accepted: 01/09/2008] [Indexed: 02/02/2023]
Abstract
PURPOSE We examined the effect of dexmedetomidine on ischemia-reperfusion injury due to tourniquet application during upper-extremity surgery by determining blood malondialdehyde and hypoxanthine levels. Alterations in aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase, lactate dehydrogenase, uric acid, and creatinine levels were also assessed. METHODS Forty patients of American Society of Anesthesiologists physical status I to II having hand and forearm surgery with tourniquet were randomly allocated into 2 groups. Brachial plexus anesthesia via axillary approach was performed for upper-limb block in all patients. In the dexmedetomidine group, a continuous infusion of dexmedetomidine (1 microg/kg for 10 minutes, followed by 0.5 microg kg(-1) h(-1)) was used until the end of surgery, whereas the control group received an equivalent volume of saline. Venous blood samples were obtained before brachial plexus anesthesia, at 1 minute before tourniquet release, and 15 minutes after tourniquet release for biochemical analysis. RESULTS Dexmedetomidine significantly attenuated plasma hypoxanthine production in the ischemia and plasma malondialdehyde production in the reperfusion periods. Blood creatine phosphokinase and uric acid levels were significantly lower in the dexmedetomidine group compared with those in the control group after reperfusion. CONCLUSIONS Our results suggest that dexmedetomidine may offer advantages by inhibiting lipid peroxidation in the case of anticipated ischemia-reperfusion injury, such as would occur in upper-extremity surgery requiring tourniquet application. TYPE OF STUDY/LEVEL OF EVIDENCE Prognostic II.
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Frink M, Kaudel CP, Hildebrand F, Pape HC, Klempnauer J, Winkler M, Krettek C, van Griensven M. FTY720 Improves Survival After Transient Ischemia and Reperfusion of the Hind Limbs. ACTA ACUST UNITED AC 2007; 63:263-7. [PMID: 17693822 DOI: 10.1097/ta.0b013e3180d0a6fc] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Ischemia and reperfusion (I/R) damage involves adhesion and transmigration of lymphocytes and neutrophils. FTY720 is an immunosuppressive agent that reduces the number of neutrophils and monocytes in peripheral blood as well as tissue lymphocyte infiltration. This study investigated the effect of FTY720 during hind limb I/R. METHODS Male C57/BL6 mice underwent temporary ligation of the infrarenal aorta for 4 hours. After 48 hours of reperfusion, animals were killed by exsanguination. Tissue myeloperoxidase content reflecting neutrophil infiltration and reverse transcription polymerase chain reaction analysis of local cytokine transcription in lung, liver, and kidney were performed. RESULTS After I/R, treatment with FTY720 improved survival and prevented upregulation of pro- and anti-inflammatory cytokines in evaluated organs, whereas no changes were detected in myeloperoxidase content after treatment with FTY720. CONCLUSIONS Whereas neutrophil infiltration was not affected by treatment with FTY720, other immunocompetent or intrinsic cells appear to be involved in changes of cytokine production in different organs.
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Affiliation(s)
- Michael Frink
- Trauma Department, Hannover Medical School, Hannover, Germany.
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Köksoy C, Oziş E, Cakmak A, Yazgan U, Okcu-Heper A, Köksoy A, Demirpençe E, Deniz Dinçer U. Simvastatin pretreatment reduces the severity of limb ischemia in an experimental diabetes model. J Vasc Surg 2007; 45:590-6. [PMID: 17257798 DOI: 10.1016/j.jvs.2006.10.048] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2006] [Accepted: 10/29/2006] [Indexed: 10/23/2022]
Abstract
OBJECTIVE The purpose of this study was to examine the effects of simvastatin pretreatment in the setting of acute limb ischemia-reperfusion injury in an experimental diabetes model that is associated with a high risk for limb loss. METHODS Adult male Sprague-Dawley rats were randomized into two groups. Diabetes was induced in the first group by intravenous streptozotocin injection. The second group served as the nondiabetic group. Eight weeks after the streptozotocin injection, half of the rats in the diabetic and the nondiabetic groups were further randomized to receive either intraperitoneal simvastatin (1 mg/kg per day) or saline treatment for 6 weeks. Bilateral hind-limb ischemia was induced for 4 hours by the tourniquet method. After 24 hours of reperfusion, tissue samples were collected from the gastrocnemius and anterior tibial muscles bilaterally for measurement of muscle edema, percentage of necrosis, and malondialdehyde (MDA), glutathione, and myeloperoxidase (MPO) levels. RESULTS Ischemic injury was more prominent in diabetic animals. The diabetic animals with limb ischemia exhibited a 7% increase in tissue edema, a 47% increase in muscle necrosis and MPO level, and a 15% reduction in glutathione levels compared with the nondiabetic animals (P < .05). Simvastatin treatment with 1 mg/kg for 6 weeks reduced the ischemic injury. Simvastatin pretreatment led to a 71% reduction in muscle necrosis in diabetic animals (P < .001). The protective effects of simvastatin pretreatment also correlated with a 23% improvement in tissue edema, a 75% reduction in tissue myeloperoxidase content, and a 71% increase in glutathione levels in diabetic animals (P < .01). Furthermore, skeletal muscle injury, characterized by tissue edema and leucosequestration, was significantly less severe with simvastatin pretreatment compared with the nondiabetic animals (P < .01). CONCLUSION Simvastatin pretreatment reduced limb ischemia-reperfusion injury in diabetic and nondiabetic animals. We conclude that simvastatin pretreatment may be a potential therapeutic intervention for skeletal muscle ischemia-reperfusion injury in the clinical setting.
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Affiliation(s)
- Cüneyt Köksoy
- Department of General Surgery, Ankara University, Ankara, Turkey.
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Ozturk K, Demir B, Oke R, Durmaz H. Dose-related effects of recombinant human interleukin-10 on hypoxia-induced skeletal muscle injury in immature rats. J Orthop Sci 2006; 11:620-5. [PMID: 17139471 DOI: 10.1007/s00776-006-1063-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2006] [Accepted: 06/30/2006] [Indexed: 10/23/2022]
Abstract
BACKGROUND The role of cytokines in the pathogenesis of skeletal muscle injury in patients with hypoxia and inflammation remains unclear. The aim of the present study was to determine the dose-related effects of recombinant human interleukin-10 (rhIL-10) on hypoxia-induced skeletal muscle injury in immature rats. METHODS The study was performed on 1-day-old Sprague-Dawley rat pups that were randomized to one of five groups: nonhypoxic controls (group 1; n=8); rats subjected to hypoxia-reoxygenation (H/O) and returned to their mothers (group 2; n=11); rats subjected to H/O, returned to their mothers, and treated with rhIL-10 (10 microg/kg per day s.c.) for 3 days (group 3; n=10); rats subjected to H/O, returned to their mothers, and treated with rhIL-10 (25 microg/kg per day s.c.) for 3 days (group 4; n=10); or rats subjected to H/O, returned to their mothers, and treated with rhIL-10 (75 microg/kg per day s.c.) for 3 days (group 5; n=10). All animals were killed on day 4, and skeletal muscle specimens were obtained to determine the tissue levels of malondialdehyde (MDA) and superoxide dismutase (SOD) and to check for any histological changes. RESULTS The polymorphonuclear leukocyte count, amount of interstitial edema, microvessel size, and area of myocyte necrosis was greater in groups 2, 3, 4, and 5 than in group 1, although the findings were significantly less prominent in groups 4 and 5 than in groups 2 and 3. MDA levels significantly increased in groups 2 and 3 compared to those in groups 1, 4, and 5. SOD values decreased significantly in groups 2 and 3 compared to those in groups 1, 4, and 5. CONCLUSIONS Administration of rhIL-10 reduced skeletal muscle injury produced by hypoxia in immature rats. Intermediate and high doses of rhIL-10 were associated with a significant reduction of skeletal muscle damage, whereas a low dose was not.
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Affiliation(s)
- Kahraman Ozturk
- Department of Orthopaedics and Traumatology, Baltalimani Metin Sabanci Training and Research Hospital for Bone Diseases, Istanbul University Faculty of Medicine, Turkey
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Ozyurt B, Iraz M, Koca K, Ozyurt H, Sahin S. Protective effects of caffeic acid phenethyl ester on skeletal muscle ischemia-reperfusion injury in rats. Mol Cell Biochem 2006; 292:197-203. [PMID: 16786192 DOI: 10.1007/s11010-006-9232-5] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2006] [Accepted: 05/11/2006] [Indexed: 12/14/2022]
Abstract
There is a great evidence that reactive oxygen species (ROS) play an important role in the pathophysiology of ischemia-reperfusion (I/R) injury in skeletal muscle. Caffeic acid phenethyl ester (CAPE) is a component of honeybee propolis. It has antioxidant, anti-inflammatory and free radical scavenger properties. The aim of this study is to determine the protective effects of CAPE against I/R injury in respect of protein oxidation, neutrophil in filtration, and the activities of xanthine oxidase (XO) and adenosine deaminase (AD) on an in vivo model of skeletal muscle I/R injury. Rats were divided into three equal groups each consisting of six rats: Sham operation, I/R, and I/R plus CAPE (I/R+CAPE) groups. CAPE was administered intraperitoneally 60 min before the beginning of the reperfusion. At the end of experimental procedure, blood and gastrocnemius muscle tissues were used for biochemical analyses. Tissue protein carbonyl (PC) levels and the activities of XO, myeloperoxidase (MPO) and AD in I/R group were significantly higher than that of control (p < 0.01, p < 0.05, p < 0.01, p < 0.005, respectively). Administration of CAPE significantly decreased tissue PC levels, MPO and XO activities in skeletal muscle compared to I/R group (p < 0.01, p < 0.05, p < 0.05, respectively). In addition, plasma creatine phosphokinase (CPK), XO and AD activities were decreased in I/R+CAPE group compared to I/R group (p < 0.05, p < 0.05, p < 0.001). The results of this study revealed that free radical attacks may play an important role in the pathogenesis of skeletal muscle I/R injury. Also, the potent free radical scavenger compound, CAPE, may have protective potential in this process. Therefore, it can be speculated that CAPE or other antioxidant agents may be useful in the treatment of I/R injury as well as diffused traumatic injury of skeletal muscle.
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Affiliation(s)
- Birsen Ozyurt
- Departments of Anatomy, Gaziosmanpasa University Faculty of Medicine, Dekanlik Binasi, Tokat, Turkey.
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Akyol A, Ulusoy H, Imamoğlu M, Cay A, Yuluğ E, Alver A, Ertürk E, Koşucu M, Beşir A, Akyol A, Ozen I. Does propofol or caffeic acid phenethyl ester prevent lung injury after hindlimb ischaemia-reperfusion in ventilated rats? Injury 2006; 37:380-7. [PMID: 16513122 DOI: 10.1016/j.injury.2006.01.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2005] [Revised: 12/16/2005] [Accepted: 01/03/2006] [Indexed: 02/02/2023]
Abstract
BACKGROUND To investigate the effects of propofol and caffeic acid phenethyl ester (CAPE) on prevention of lung injury as a remote organ after performing hindlimb ischaemia-reperfusion (IR) in a rat model. METHODS The animals were divided randomly into one of four groups: sham, no IR (n = 8), control, IR, (n = 8), CAPE group, IR with CAPE, (n = 8), propofol group, IR with P, (n = 8). After the rats were anaesthetised, the animals in the CAPE group received CAPE of 10 micromol, in the propofol group received propofol 50 mg/kg, in the control group received a similar volume of saline solution by means of intraperitoneal injection 1 h before reperfusion. After 4 h of ischaemia the tourniquet was removed and the animals were released for reperfusion for 4 h thereafter. At the end of the reperfusion period, a median sternotomy was performed. A blood sample was obtained for plasma malondialdehyde (MDA). The lung tissues were also removed for MDA assays, myeloperoxidase (MPO) activity, and histopathological examination. RESULTS Plasma and lung MDA levels, and lung MPO activity were significantly higher in the control group compared to the other groups (p < 0.0005). In the CAPE group, these were significantly lower compared to the control group (p < 0.0005). Also, propofol caused a marked reduction in the MDA levels and MPO activity compared with control group (p < 0.0005), with no significant difference compared to that of the sham group. Histopathologically, the scores resulted in a grade zero (8/8) in the sham group, 3 (3/8) or 4 (5/8) in the control group, 1 (2/8) or 2 (6/8) in the CAPE group, and 1 (3/8) or 2 (5/8) in the propofol group. CONCLUSION Propofol and CAPE seem to be effective in protecting against lung injury caused by increased oxidative stress and neutrophil accumulation after hindlimb IR in a rat model.
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Affiliation(s)
- Ahmet Akyol
- Department of Anesthesiology and Critical Care, Karadeniz Technical University, Faculty of Medicine, Trabzon, Turkey.
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Jia CJ, Dai CL, Zhang X, Cui K, Xu F, Xu YQ. Alanyl-glutamine dipeptide inhibits hepatic ischemia-reperfusion injury in rats. World J Gastroenterol 2006; 12:1373-8. [PMID: 16552804 PMCID: PMC4124313 DOI: 10.3748/wjg.v12.i9.1373] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [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 protective effect and mechanism of alanyl-glutamine dipeptide (Ala-Gln) against hepatic ischemia-reperfusion injury in rats.
METHODS: Rats were divided into group C as normal control Group (n=16) and group G as alanyl-glutamine pretreatment (n=16). Rats were intravenously infused with 0.9% saline solution in group C and Ala-Gln -enriched (2% glutamine) 0.9% saline solution in group G via central venous catheter for three days. Then all rats underwent hepatic warm ischemia for 30 min followed by different periods of reperfusion. Changes in biochemical parameters, the content of glutathione (GSH) and the activity of superoxide dismutase (SOD) in liver tissue, Bcl-2 and Bax protein expression and morphological changes of liver tissue were compared between both groups.
RESULTS: One hour after reperfusion, the levels of liver enzymes in group G were significantly lower than those in group C (P<0.05). Twenty-four hours after reperfusion, the levels of liver enzymes in both groups were markedly recovered and the levels of liver enzyme in group G were also significantly lower than those in group C (P <0.01). One and 24 h after reperfusion, GSH content in group G was significantly higher than that in group C (P <0.05). There was no statistical difference in activities of SOD between the two groups. One and 24 h after reperfusion, the positive expression rate of Bcl-2 protein was higher in group G than in group C (P <0.05) and the positive expression rate of Bax protein was lower in group G than in group C (P < 0.05). Histological and ultrastructural changes of liver tissue were inhibited in group C compared to group G.
CONCLUSION: Our results suggest that Ala-Gln pretreatment provides the rat liver with significant tolerance to warm ischemia-reperfusion injury, which may be mediated partially by enhancing GSH content and regulating the expression of Bcl-2 and Bax proteins in the liver tissue.
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Affiliation(s)
- Chang-Jun Jia
- Department of Hepatobiliary Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning Province, China
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Fischer CP, Hong JC. Method of pyloric reconstruction and impact upon delayed gastric emptying and hospital stay after pylorus-preserving pancreaticoduodenectomy. J Gastrointest Surg 2006; 10:215-9. [PMID: 16455453 DOI: 10.1016/j.gassur.2005.07.017] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2005] [Accepted: 07/21/2005] [Indexed: 01/31/2023]
Abstract
Preservation of the pylorus at the time of pancreaticoduodenectomy has been associated with equal oncological outcomes when compared to the classical Whipple operation. Multiple studies have demonstrated that pylorus-preserving pancreaticoduodenectomy (PPPD) has equal or superior outcomes regarding quality of life when compared with the traditional Whipple operation, but many studies have suggested a higher incidence of delayed gastric emptying (DGE). DGE prolongs hospital stay, and its association with PPPD has hampered its adoption by many pancreatic surgery centers. We describe a novel surgical technique for the prevention of delayed gastric emptying following pylorus-preserving pancreaticoduodenectomy. The technique of pyloric dilatation appears to decrease the incidence of delayed gastric emptying and facilitates earlier hospital discharge, when compared with standard pylorus preserving pancreaticoduodenectomy.
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Affiliation(s)
- Craig P Fischer
- Department of Surgery, The Methodist Hospital, Weill Medical College of Cornell University, Houston, TX 77030, USA.
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Salman AE, Dal D, Salman MA, Iskit AB, Aypar U. The effect of ketamine on acute muscular ischaemia reperfusion in rats. Eur J Anaesthesiol 2006; 22:712-6. [PMID: 16163919 DOI: 10.1017/s0265021505001171] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND OBJECTIVE The aim of this study was to investigate any possible protective effect of ketamine in acute muscular ischaemia and reperfusion injury by measuring malondialdehyde using thiobarbituric acid assay in rats. METHODS Twelve female Wistar albino rats were anaesthetized with chloral hydrate and randomly assigned into two groups to receive ketamine 1 mg kg(-1) min(-1) or saline infusion. Blood and gastrocnemius muscle samples were obtained 10 min after onset of infusion, before ischaemia. Then, femoral arteries were clamped for 30 min. Blood and muscle samples were obtained at the 30th minute of ischaemia and 10 min after reperfusion. RESULTS Muscle malondialdehyde concentrations were 27.88 +/- 2.45, 27.62 +/- 3.98 before ischaemia, 32.10 +/- 4.19, 30.77 +/- 2.73 in the 30th minute of ischaemia and 44.34 +/- 2.45, 34.83 +/- 2.78 after reperfusion in saline and ketamine-treated rats, respectively (nmol g(-1), mean +/- SD). The muscle malondialdehyde level after reperfusion was lower in ketamine-treated rats compared to saline group (P < 0.002). Plasma malondialdehyde levels were 3.77 +/- 0.16, 3.78 +/- 0.18 before ischaemia, 3.81 +/- 0.25, 4.00 +/- 0.86 at the 30th minute of ischaemia and 4.00 +/- 0.53, 3.94 +/- 0.95 after reperfusion, respectively, in saline and ketamine-treated rats (micromol L(-1), mean +/- SD). The effect of ketamine on muscular malondialdehyde was not observed in concurrent plasma malondialdehyde levels. CONCLUSION Ketamine was found to attenuate acute ischaemia-reperfusion injury in muscle tissue in rats (muscular protective). Ketamine may attenuate lipid peroxidation in muscle tissue in tourniquet-requiring manoeuvres.
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Affiliation(s)
- A E Salman
- Hacettepe University, Faculty of Medicine, Department of Anaesthesiology, Ankara, Turkey
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Jia CJ, Dai CL, Zhang X, Xu F, Cui K, Xu YQ. Effects of glutamine on glutathione content and expression of Bcl-2 and Bax protein during hepatic ischemia and reperfusion injury in rats. Shijie Huaren Xiaohua Zazhi 2005; 13:2297-2301. [DOI: 10.11569/wcjd.v13.i19.2297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of alanyl-glutamine dipeptiven (Ala-Gln) on the content of glutathione (GSH) and the expression of Bcl-2 and Bax protein during hepatic ischemia and reperfusion injury (HIRI) in rats.
METHODS: A total of 48 Wistar rats were randomly divided into glutamine group (group G) and control group (group C), which were pretreated with Gln and normal saline, respectively. The liver was subjected to warm ischemia by Pringle method for 30 min, and then reperfused. The serum samples were colleted 1 and 24 h after the reperfusion, and the level of serum ALT was measured. The GSH content and histopathological changes were detected in the liver tissues. The expression of Bcl-2 and Bax protein in the liver tissues were detected by immunohistochemistry.
RESULTS: The level of serum ALT was significantly lower in group G than that in group C 1 and 24 h after the reperfusion (8.3 ± 2.0 mkat/L vs 13.7± 5.5 mkat/L, P < 0.05; 2.9 ± 2.5 mkat/L vs 9.1 ± 4.3 mkat/L, P < 0.01), but the GSH content was significantly higher in group G than that in group C (1216.09 ± 152.78 mg/g vs 856.68 ± 117.64 mg/g, P < 0.01; 899.73 ± 57.75 mg/g vs 800.50 ± 94.79 mg/g, P < 0.05). The histopathological changes were significantly slighter in group G than those in group C. One and twenty-four hours after the reperfusion, the positive rate of Bcl-2 protein expression was significantly higher in group G than that in group C (100.0% vs 37.5%, P < 0.05; 87.5% vs 25.0%, P < 0.05), while the positive rate of Bax protein expression was significantly lower in group G than that in group C (25.0% vs 87.5%, P < 0.05; 25.0% vs 87.5%, P < 0.05).
CONCLUSION: Ala-Gln (Gln) can protect rats against HIRI, and the mechanism may relate to the enhancement of GSH content and the regulation of Bcl-2, Bax protein expression.
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Saricaoglu F, Dal D, Salman AE, Doral MN, Klnç K, Aypar Ü. Ketamine Sedation During Spinal Anesthesia for Arthroscopic Knee Surgery Reduced the Ischemia-Reperfusion Injury Markers. Anesth Analg 2005; 101:904-909. [PMID: 16116012 DOI: 10.1213/01.ane.0000159377.15687.87] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
We studied the effect of ketamine sedation on oxidative stress during arthroscopic knee surgery with tourniquet application by determining blood and tissue malonyldialdehyde (MDA) and hypoxanthine (HPX) levels. Thirty ASA I-II patients undergoing arthroscopic knee surgery with tourniquet were randomly divided into two groups. Spinal anesthesia induced with 12.5 mg bupivacaine was administered to all patients. In the ketamine group, after IV administration of 0.01 mg/kg midazolam, a continuous infusion of ketamine (0.5 mg . kg(-1) . h(-1)) was used until the end of surgery whereas the placebo group received a volume-equivalent placebo infusion. Ramsey Sedation Scale (RSS) was used for assessing the sedation level. Venous blood and synovial membrane tissue samples were obtained before ketamine infusion, at 30 min of tourniquet ischemia, and at 5 min after tourniquet deflation for MDA and HPX measurements. Tissue MDA and HPX levels were significantly less in the ketamine group than the control group after reperfusion. RSS scores were higher in the ketamine group without any adverse effect. We conclude that ketamine sedation attenuates lipid peroxidation markers in arthroscopic knee surgery with tourniquet application.
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Affiliation(s)
- Fatma Saricaoglu
- *Department of Anaesthesiology and Reanimation, †Department of Sports Medicine and Orthopaedics, and the ‡Department of Biochemistry, Hacettepe University Faculty of Medicine, Ankara, Turkey
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Saricaoglu F, Dal D, Salman AE, Atay OA, Doral MN, Salman MA, Kilinç K, Aypar U. Effect of low-dose N-acetyl-cysteine infusion on tourniquet-induced ischaemia-reperfusion injury in arthroscopic knee surgery. Acta Anaesthesiol Scand 2005; 49:847-51. [PMID: 15954970 DOI: 10.1111/j.1399-6576.2005.00722.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Temporary occlusion of blood flow is used during arthroscopic knee surgery in order to provide a bloodless surgical field. The resulting ischaemia-reperfusion causes lipid peroxidation, which contributes to tissue injury. The aim of the study was to investigate the effect of low-dose n-acetyl cysteine (NAC) infusion on oxidative stress by determining malondialdehyde (MDA) levels during arthroscopic knee surgery. METHODS Thirty patients, ASA I - II, undergoing arthroscopic knee debridement under a tourniquet were divided into NAC and control groups. Anaesthesia was induced with propofol, fentanyl and vecuronium bromide and maintained with desflurane in an equal parts O(2)-N(2)O mixture. In the NAC group, an infusion of NAC, 5 mg kg(-1).h(-1), was started after intubation, and continued until extubation. An equal volume of saline was infused to the control group. Duration of ischaemia, anaesthesia time, total dose of NAC infused were also recorded. Venous blood and synovial membrane tissue samples were obtained 10 min after the onset of NAC infusion but before tourniquet inflation (t1), after 30 min of ischaemia (t2), and after 5 min of reperfusion following tourniquet release (t3). RESULTS Plasma MDA levels were significantly lower in the NAC group on reperfusion. There were no differences between the groups in tissue MDA levels at ischaemia and reperfusion times. CONCLUSION Low-dose n-acetyl cysteine infusion attenuates lipid peroxidation and ischaemia-reperfusion injury in arthroscopic knee surgery requiring tourniquet application.
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Affiliation(s)
- F Saricaoglu
- Department of Anaesthesiology and Reanimation, Hacettepe University Faculty of Medicine, Ankara, Turkey.
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Kanko M, Maral H, Akbas MH, Ozden M, Bulbul S, Omay O, Yavuz S, Berki KT. Protective effects of clopidogrel on oxidant damage in a rat model of acute ischemia. TOHOKU J EXP MED 2005; 205:133-9. [PMID: 15673971 DOI: 10.1620/tjem.205.133] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Reperfusion injury is a consequence of inadequate energy supply and acidosis in ischemic tissues and a chain of events triggered by oxygen-derived free radicals released in response to exposure of oxygen. In this study, we aimed to assess the effects of clopidogrel, an antithrombotic agent, on experimental ischemia-reperfusion model in rats. The ischemia was performed by blockade of the circulation of right lower extremity at trochanter major level for 6 hours. Then, the extremity was reperfused for 4 hours. Another group of rats pretreated with clopidogrel (0.2 mg/kg/day) for 10 days prior to ischemia-reperfusion. After the reperfusion period, all rats were anesthetized with ketamine. Blood and tissue samples from the gastrocnemius muscle, liver and lungs were taken for the measurement of malondialdehyde (MDA), glutathione (GSH) levels and superoxide dismutase (SOD) activity. The results revealed that clopidogrel prevented the increase in MDA level and the decrease in GSH level and SOD activity caused by ischemia-reperfusion both in tissue samples and plasma. These findings suggest that clopidogrel is beneficial in prevention of ischemia-reperfusion injury probably via its effects on inflammatory cells, platelets, and endothelial cells.
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Affiliation(s)
- Muhip Kanko
- Department of Cardiovascular Surgery, Kocaeli University School of Medicine, Kocaeli, Turkey.
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Koksal C, Bozkurt AK, Sirin G, Konukoglu D, Ustundag N. Aprotinin ameliorates ischemia/reperfusion injury in a rat hind limb model. Vascul Pharmacol 2005; 41:125-9. [PMID: 15607495 DOI: 10.1016/j.vph.2004.05.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/21/2004] [Indexed: 11/26/2022]
Abstract
The aim of the study was to investigate the protective effect of aprotinin in a rat hind limb ischemia/reperfusion (I/R) model. A well-known antioxidant, alpha-tocopherol, was also tested for comparison. Ischemia was induced for 4 h by vascular clamping of the iliac arteries of 24 Sprague-Dawley rats, followed by 1 h of reperfusion. Muscle injury was evaluated in three groups: a saline group, an alpha-tocopherol group and an aprotinin group. Blood pH, pO2, pCO2, HCO3, creatine kinase (CPK), lactate dehyrogenase (LDH) and thiobarbituric acid reactive substances (TBARS) as well as muscle TBARS were measured at the end of the reperfusion. Muscle tissue samples were taken for histological examination. alpha-Tocopherol and aprotinin groups showed a significant amelioration of plasma CPK (p=0.002, p=0.002), LDH (p=0.004, p=0.004) and muscle tissue TBARS (p=0.001, p=0.001) compared with the control. Plasma TBARS were significantly lower in the aprotinin group compared with the control (p=0.017). Also, tissue TBARS was significantly lower in the aprotinin group than the alpha-tocopherol group (p<0.001). Neutrophil infiltration was less prominent in the alpha-tocopherol and aprotinin groups compared to the control (p=0.006, p=0.001). These results suggest that aprotinin, a potent anti-inflammatory drug, is more useful than alpha-tocopherol, a powerful antioxidant, for attenuating muscle injury after I/R.
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Affiliation(s)
- Cengiz Koksal
- Istanbul University, Cerrahpasa Medical Faculty, Department of Cardiovascular Surgery, P.O. Box 26, Cerrahpasa, 34301, Istanbul, Turkey.
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Odland R, Schmidt AH, Hunter B, Kidder L, Bechtold JE, Linzie BM, Pedowitz RA, Hargens AR. Use of tissue ultrafiltration for treatment of compartment syndrome: a pilot study using porcine hindlimbs. J Orthop Trauma 2005; 19:267-75. [PMID: 15795576 DOI: 10.1097/01.bot.0000155308.20133.71] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
OBJECTIVES To demonstrate the efficacy of compartment syndrome ultrafiltration for the treatment of acute compartment syndrome in an animal model. Our hypothesis is the removal of interstitial fluid will result in a reduction of intramuscular pressure compared with untreated controls in a model of bilateral induced compartment syndrome. DESIGN Controlled experimental model. SETTING Animal research facility. PATIENTS/PARTICIPANTS Three pairs of porcine hindlimbs. INTERVENTION Acute compartment syndrome was created in the pig hindlimb by infusion of saline to maintain the intramuscular pressure 30 mm Hg greater than the animal's mean arterial pressure for 8 hours. After a 2-hour reperfusion interval, ultrafiltration (removal of fluid through 1 mm diameter porous catheters, connected to -500 mm Hg suction) was commenced in 1 limb only and continued for 9.5 hours. MAIN OUTCOME MEASURES Intramuscular pressure, ultrafiltrate volume, ultrafiltrate and serum levels of creatine kinase and lactate dehydrogenase, histologic measurement of extracellular and intracellular edema, as well as the degree of cellular necrosis. RESULTS Intramuscular pressure tended to be lower on the treated side at the end of the treatment period [treated leg: 9.3 +/- 4.0 mm Hg (+/- SE), control leg: 19.3 +/- 1.4 mm Hg, P = 0.03]. Analysis of ultrafiltrate fluid showed that levels of creatine kinase and lactate dehydrogenase were elevated compared with serum levels. Creatine kinase levels in serum were measured at 4150 +/- 780 U/L, whereas ultrafiltrate levels of creatine kinase were 28,700 +/- 17,700 U/L (+/- SE) (P = 0.1). Lactate dehydrogenase was measured at 1950 +/- 180 U/L in serum, but markedly elevated in ultrafiltrate [160,000 +/- 88,900 U/L (+/- SE), P = 0.05]. Quantification of cellular and interstitial dimensions showed no difference in control and experimental limbs. Quantification of the degree of muscle necrosis revealed 6.1 +/- 2.7% necrosis in the treated limb compared to 11.3 +/- 1.6% necrosis in the control group (P = 0.02, df = 2, 1-tailed paired t test). CONCLUSION This pilot study demonstrates the feasibility of tissue ultrafiltration for reduction of intramuscular pressure in this porcine model. Further studies are underway. Compartment syndrome ultrafiltration may be useful prophylactically in patients at risk for acute compartment syndrome. Sampling of interstitial fluid and frequent measurement of intramuscular pressure may allow earlier diagnosis and treatment of acute compartment syndrome, whereas the reduction of tissue pressure by compartment syndrome ultrafiltration may prevent acute compartment syndrome from occurring. Additionally, compartment syndrome ultrafiltration will not hinder the ability of clinicians to use the clinical examination and pressure monitoring as the gold standard.
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Affiliation(s)
- Rick Odland
- Department of Otolaryngology, Hennepin County Medical Center, Minneapolis, MN 55415, USA.
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Thomas S, Prabhu R, Balasubramanian KA. Surgical manipulation of the intestine and distant organ damage—protection by oral glutamine supplementation. Surgery 2005; 137:48-55. [PMID: 15614281 DOI: 10.1016/j.surg.2004.04.038] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
BACKGROUND The intestine is increasingly recognized as a primary effector of distant organ damage, such as the lung, after any abdominal surgery. Earlier studies have shown that surgical manipulation of the intestine induces generation of reactive oxygen species in the intestine, resulting in mucosal and lung damage. Because glutamine is preferentially used by the small intestine as an energy source, this study examined the effect of glutamine and glutamic acid on intestinal and lung damage after surgical manipulation. METHODS Controls and rats were pretreated for 7 days with 2% glutamine or glutamic acid, or the isonitrogenous amino acids glycine or alanine in the diet and subjected to surgical manipulation of the intestine. The intestine and lung were assessed for damage, and protection offered by various amino acids was studied. RESULTS Surgical manipulation resulted in oxidative stress in the intestine as evidenced by increased xanthine oxidase activity and decreased antioxidant status. Enterocyte mitochondria were also functionally impaired with altered calcium flux, decreased respiratory control ratio, and increased swelling. Gut manipulation also resulted in neutrophil infiltration and oxidative stress in the lung as assessed by an increase in myeloperoxidase activity, lipid peroxidation, and antioxidant status. Glutamine or glutamic acid supplementation for 7 days before surgical manipulation showed a protective effect against the intestinal and lung damage. CONCLUSIONS This study suggests that preoperative enteral glutamine or glutamic acid supplementation attenuates intestinal and lung damage in rats during surgical manipulation and that this effect might offer protection from postsurgical complications.
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Affiliation(s)
- Simmy Thomas
- Department of Gastrointestinal Sciences, Wellcome Trust Research Laboratory, Christian Medical College, Ida Scudder Road, Vellore-632004, India
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N/A. N/A. Shijie Huaren Xiaohua Zazhi 2004; 12:2481-2483. [DOI: 10.11569/wcjd.v12.i10.2481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Irie H, Kato T, Ikebe K, Tsuchida T, Oniki Y, Takagi K. Antioxidant effect of MCI-186, a new Free-Radical scavenger, on ischemia-reperfusion injury in a rat hindlimb amputation model. J Surg Res 2004; 120:312-9. [PMID: 15234228 DOI: 10.1016/j.jss.2003.12.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2003] [Indexed: 10/26/2022]
Abstract
BACKGROUND A newly synthesized free-radical scavenger, MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-1), was recently approved in Japan for treating acute brain infarction. The purpose of this study was to investigate whether or not MCI-186 is effective in reducing ischemia-reperfusion injury in the extremities. MATERIALS AND METHODS Warm ischemia was sustained for 4 hours. The animals were divided into 4 groups: (1) sham group, (2) control group (saline injection), (3) MCI group (MCI-186 injection), and (4) EPC group (EPC-K1 [(l-ascorbic acid 2-[3,4-dihydro-2, 5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl hydrogen phosphate] potassium salt], a hydroxyl-radical scavenger, injection). Wet and dry (W/D) weights of the gastrocnemius and tibialis anterior muscles, muscle contractile function, and serum levels of creatine phosphokinase (CPK), lactate dehydrogenase (LDH), glutamic oxaloacetic transminase (GOT), and mitochondrial glutamic oxaloacetic transminase (GOT-m) were measured after 24 h of reperfusion. The cytotoxic aldehydes malondialdehyde and 4-hydroxy-2-nonenal as indices of lipid peroxidation (LPO), and neutrophil-specific enzyme myeloperoxidase (MPO) as an index of neutrophil infiltration, were measured in the gastrocnemius muscle. RESULTS Contractile functions in the MCI and EPC groups were significantly better than in the control group. In the tibialis anterior muscle, the contractile function was better in the MCI group than in the EPC group. W/D ratios and serum levels of CPK, LDH, GOT, and GOT-m were lower in the sham and MCI groups than in the control group. Levels of LPO and MPO activity were significantly lower in the MCI and EPC groups than in the control group. Histological findings demonstrated that inflammatory tissue reactions rarely occurred in the MCI group. CONCLUSION MCI-186 is effective in preventing ischemia-reperfusion injury in extremities. MCI-186 seems to have promise as a therapeutic agent, because it prevents ischemia-reperfusion injury even in the tibialis anterior muscle, which contains fast-twitch glycolytic fibers, known to be very susceptible to ischemic insult.
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Affiliation(s)
- H Irie
- Department of Clinical Research, National Saishunso Hospital, 2659 Suya, Nishigoushi-machi, Kumamoto 861-1102, Japan
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Thomas S, Balasubramanian KA. Role of intestine in postsurgical complications: involvement of free radicals. Free Radic Biol Med 2004; 36:745-56. [PMID: 14990353 DOI: 10.1016/j.freeradbiomed.2003.11.027] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2003] [Revised: 11/10/2003] [Accepted: 11/14/2003] [Indexed: 12/14/2022]
Abstract
Surgery at any location in the body leads to surgical stress response and alterations in normal body homeostasis. The intestine is extremely sensitive to surgical stress even at remote locations and the gastrointestinal tract plays an important role in the development of postsurgical complications such as sepsis, the systemic immune response syndrome (SIRS), and multiple organ failure syndrome (MOFS). The generation of free radicals and subsequent biochemical alterations at the cellular and subcellular level in the intestine has been suggested to play an important role in this process. These oxidative stress-induced events in the mucosa might act as an initiator of distant organ damage and also facilitate bacterial adherence onto the epithelium and translocation into the systemic circulation. This review attempts to highlight the important role of intestine and oxygen free radicals in initiating post-surgical complications.
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Affiliation(s)
- Simmy Thomas
- The Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College, Vellore 632004, India
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Joon Suh G, Youn YK, Song HG, Eui Rhee J, Eun Jung S. The effect of glutamine on inducible nitric oxide synthase gene expression in intestinal ischemia-reperfusion injury. Nutr Res 2003. [DOI: 10.1016/s0271-5317(02)00479-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Lu K, Liang CL, Cho CL, Chen HJ, Hsu HC, Yiin SJ, Chern CL, Chen YC, Lee TC. Oxidative stress and heat shock protein response in human paraspinal muscles during retraction. J Neurosurg 2002; 97:75-81. [PMID: 12120656 DOI: 10.3171/spi.2002.97.1.0075] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECT The need for wide dissection and forceful retraction of paraspinal muscles often required for posterolateral lumbar fusion and fixation may severely jeopardize the muscles, structurally and functionally. The underlying pathophysiology of muscle damage may involve both mechanical and ischemic mechanisms. On the other hand, the surgery-related stress may trigger certain protective responses within the insulted paraspinal muscles. This study was conducted to assess the relationship between the oxidative stress and the stress response mediated by heat shock protein 70 (HSP70) induction within paraspinal muscles being retracted. METHODS Multifidus muscle specimens were surgically obtained before, during, and after retraction in patients with lumbar spondylolisthesis undergoing posterolateral lumbar fusion, pedicle fixation, and laminectomy. Muscle samples were analyzed to determine HSP70 and malondialdehyde (MDA) levels. Both HSP70 expression and MDA production within multifidus muscle cells were increased significantly by retraction. Expression of HSP70 then decreased after a peak at 1.5 hours of retraction, whereas MDA levels remained elevated even after release of retractors for reperfusion of the muscles. Analysis of histopathological and immunohistochemical evidence indicated that the decline of HSP70 synthesis within muscle cells after prolonged retraction was the result of severe muscle damage. CONCLUSIONS Results of this study highlight the deleterious effect of intraoperative retraction on human paraspinal muscles at the cellular and molecular levels. The authors also found that intraoperative maneuvers aimed at reducing the oxidative stress within the paraspinal muscles may help to attenuate surgery-related paraspinal muscle damage.
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Affiliation(s)
- Kang Lu
- Department of Neurosurgery, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung Hsien, Taiwan.
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