Abstract
Purpose
To evaluate the combined effect of α-tocopherol and gadolinium chloride (GdCl3) in reducing lipid peroxidation after severe hepatic ischemia/reperfusion (IR) injury.
Methods
Sixty male Wistar rats, 200–250 g, were randomly divided into six equal groups. There were two sham operation (SHAM) groups, two untreated IR groups, and two IR groups treated with GdCl3 and α-tocopherol (IRGT). After 60 min of total hepatic ischemia and 120 min reperfusion, one of each group was killed, liver samples were taken for malondialdehyde (MDA) and myeloperoxidase (MPO) analysis and light microscopy examination, and blood samples were analyzed for aspartate (AST) and alanine (ALT) transaminase, lactate dehydrogenase (LDH), and α-tocopherol content. The remaining groups were monitored for survival rate determination.
Results
The mean MDA and MPO values in the SHAM, IR, and IRGT groups, respectively, were 1.117, 1.476, and 0.978 nmol/g wet tissue and 1.49, 6.26, and 1.78 (U/g). The mean α-tocopherol values in the SHAM, IR, and IRGT groups, respectively, were 10.4, 1.9, and 12 µmol/l. The mean serum AST, ALT, and LDH values were significantly higher in the IR group than in the SHAM group (P < 0.001), and significantly lower in the IRGT group than in the IR group (P < 0.001). Light microscopy examination revealed more severe congestion and vacuolization in the IR group than in the SHAM group, and minimal congestion and vacuolization in the IRGT group. Survival was significantly higher in the IRGT group than in the IR group.
Conclusion
The administration of GdCl3 and α-tocopherol is likely to protect the liver against lipid peroxidation by suppressing Kupffer cell and polymorphonuclear leukocyte activation and enhancing endogenous antioxidant activity.
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References
KI Bzeizi R Jalan JN Plevris PC Hays (1997) ArticleTitlePrimary graft dysfunction after liver transplantation: from pathogenesis to prevention Liver Transpl Surg 3 137–48 Occurrence Handle10.1002/lt.500030206 Occurrence Handle1:STN:280:DyaK1c%2FgtlentA%3D%3D Occurrence Handle9346727
BG Rosser GJ Gores (1995) ArticleTitleLiver cell necrosis: cellular mechanisms and clinical implications Gastroenterology 108 252–75 Occurrence Handle10.1016/0016-5085(95)90032-2 Occurrence Handle1:STN:280:ByqC3cvmsVc%3D Occurrence Handle7806049
A Nakamitsu E Hiyama Y Imamura Y Matsuura T Yokoyama (2001) ArticleTitleKupffer cell function in ischemic and nonischemic livers after hepatic partial ischemia-reperfusion Surg Today 31 140–8 Occurrence Handle10.1007/s005950170198 Occurrence Handle1:STN:280:DC%2BD3MzitlagtA%3D%3D Occurrence Handle11291708
H Jaeschke AP Bautista Z Spolarics JJ Spitzer (1992) ArticleTitleSuperoxide generation by neutrophils and Kupffer cells during in vivo reperfusion after ischemia in rats J Leukoc Biol 52 377–82 Occurrence Handle1:CAS:528:DyaK3sXlslGjug%3D%3D Occurrence Handle1328439
M Kukan K Vajdova J Horecky A Nagyova HM Mehendale T Trnovec (1997) ArticleTitleEffects of blockade of Kupffer cells by gadolinium chloride on hepatobiliary function in cold ischemia-reperfusion injury of rat liver Hepatology 26 1250–7 Occurrence Handle1:CAS:528:DyaK2sXntl2jt7s%3D Occurrence Handle9362369
H Imamura F Sutto A Brault PM Huet (1995) ArticleTitleRole of Kupffer cells in cold ischemia/reperfusion injury of rat liver Gastroenterology 109 189–97 Occurrence Handle10.1016/0016-5085(95)90284-8 Occurrence Handle1:STN:280:ByqA3Mjltlw%3D Occurrence Handle7797017
S Suzuki LH Toledo-Pereyra F Rodriguez F Lopez (1994) ArticleTitleRole of Kupffer cells in neutrophil activation and infiltration following total hepatic ischemia and reperfusion Shock 42 204–9 Occurrence Handle1:STN:280:ByuA3szgtFc%3D
D Ruttinger B Vollmar GA Wanner K Messmer (1996) ArticleTitleIn vivo assessment of hepatic alterations following gadolinium chloride-induced Kupffer cell blockade J Hepatol 25 960–7 Occurrence Handle1:STN:280:ByiC28%2FitFQ%3D Occurrence Handle9007726
B Vollmar D Ruttinger GA Wanner R Leiderer MD Menger (1998) ArticleTitleFailure of Kupffer cell blockade to prevent disseminated intravascular coagulation in endotoxemic rats despite improved survival Langenbecks Arch Surg 383 75–80 Occurrence Handle10.1007/s004230050133 Occurrence Handle9627175
D Ruttinger B Vollmar B Kempter K Messmer (1996) ArticleTitleModulation of Kupffer cell activity by gadolinium chloride in endotoxemic rats Shock 6 434–41 Occurrence Handle8961394
J Gugenheim F Crafa G Dammerota A Evangelista MC Saint-Paul C Cavanel et al. (1994) ArticleTitleRole of non-parenchymal liver cells in ischemia-reperfusion liver injury: protective effects of muramyl dipeptide Transpl Int 7 Suppl 1 S139–43
JC Cutrin A Boveris B Zingaro G Corvetti G Poli (2000) ArticleTitleIn situ determination by surface chemiluminescence of temporal relationships between evolving warm ischemia-reperfusion injury in rat liver and phagocyte activation and recruitment Hepatology 31 622–32 Occurrence Handle1:CAS:528:DC%2BD3cXhvFCqu7c%3D Occurrence Handle10706552
K Vajdova R Smrekova M Kukan J Jakubovsky N van Rooijen J Horecky et al. (2000) ArticleTitleEndotoxin-induced aggravation of preservation-reperfusion injury of rat liver and its modulation J Hepatol 32 112–20 Occurrence Handle1:CAS:528:DC%2BD3cXnsFCrsA%3D%3D Occurrence Handle10673075
D Sindram RJ Porte MR Hoffman RC Bentley PA Clavien (2001) ArticleTitleSynergism between platelets and leukocytes in inducing endothelial cell apoptosis in the cold ischemic rat liver: a Kupffer cell-mediated injury FASEB J 15 1230–2 Occurrence Handle1:CAS:528:DC%2BD3MXlvVOmt7Y%3D Occurrence Handle11344097
C Bremer BU Bradford KJ Hunt KT Knecht HD Connor RP Mason et al. (1994) ArticleTitleRole of Kupffer cells in the pathogenesis of hepatic reperfusion injury Am J Physiol 267 G630–6 Occurrence Handle1:CAS:528:DyaK2cXmvFygsrY%3D Occurrence Handle7943328
Z Zhong HD Connor RP Mason W Qu W Gao JJ Lemasters et al. (1995) ArticleTitleRole of Kupffer cells in reperfusion injury in fat-loaded livers from ethanol-treated rats J Pharmacol Exp Ther 275 1512–17 Occurrence Handle1:STN:280:BymC3cfmsV0%3D Occurrence Handle8531123
DE Giakoustidis S Iliadis D Tsantilas G Papageorgiou N Kontos E Kostopoulou et al. (2003) ArticleTitleBlockade of Kupffer cells by gadolinium chloride reduces lipid peroxidation and protects liver from ischemia/reperfusion injury Hepatogastroenterology 50 1587–92 Occurrence Handle1:CAS:528:DC%2BD3sXot1CltbY%3D Occurrence Handle14571792
H Jaeschke (1995) ArticleTitleMechanisms of oxidant stress-induced acute tissue injury PSEBM 209 104–11 Occurrence Handle1:CAS:528:DyaK2MXmtVCksr0%3D
S Suzuki LH Toledo-Pereyra (1994) ArticleTitleInteleukin 1 and tumor necrosis factor production as the initial stimulants of liver ischemia and reperfusion injury J Surg Res 57 253–8 Occurrence Handle1:CAS:528:DyaK2cXmtVeiu78%3D Occurrence Handle7518017
H Jaeschke (1997) ArticleTitleCellular adhesion molecules: regulation and functional significance in the pathogenesis of liver diseases Am J Physiol 273 G602–11 Occurrence Handle1:CAS:528:DyaK2sXmtlentL0%3D Occurrence Handle9341049
KJ Simpson NW Lukacs L Colleti RM Strieter SL Kunkel (1997) ArticleTitleCytokines and the liver J Hepatol 27 1120–32 Occurrence Handle10.1016/S0168-8278(97)80160-2 Occurrence Handle1:CAS:528:DyaK1cXks1Km Occurrence Handle9453442
L Kuiper A Brouwer DL Knook TJC van Berkel (1994) Kupffer and sinusoidal endothelial cells JM Arias JL Boyer N Fausto WB Jacoby DA Schachter DA Shafritz (Eds) The liver biology and pathobiology EditionNumber3rd ed Raven Press New York
K Decker (1990) ArticleTitleBiologically active products of stimulated liver macrophages (Kupffer cells) Eur J Biochem 192 245–61 Occurrence Handle10.1111/j.1432-1033.1990.tb19222.x Occurrence Handle1:CAS:528:DyaK3cXlvV2hsbg%3D Occurrence Handle2170121
H Jaeschke A Farhood (1991) ArticleTitleNeutrophil and Kupffer cell-induced oxidant stress and ischemia-reperfusion injury in rat liver Am J Physiol 260 G355–62 Occurrence Handle1:CAS:528:DyaK3MXhs1Wrt7g%3D Occurrence Handle2003603
HV Shibuya N Ohkohchi K Seya S Satomi (1997) ArticleTitleKupffer cells generate superoxide anions and modulate reperfusion injury in rat livers after cold preservation Hepatology 25 356–60 Occurrence Handle1:CAS:528:DyaK2sXisFGntL8%3D Occurrence Handle9021947
H Jaeschke A Farhood A Bautista Z Spolarics J Spitzer (1993) ArticleTitleComplement activates Kupffer cells and neutrophils during reperfusion after hepatic ischemia Am J Physiol 264 G801–9 Occurrence Handle1:CAS:528:DyaK3sXksVOit74%3D Occurrence Handle8476062
I Marzi K Cowper Y Takei K Lindert JJ Lemasters RG Thurman (1991) ArticleTitleMethyl palmitate prevents Kupffer cells activation and improves survival after orthotopic liver transplantation in the rat Transpl Int 4 215–20 Occurrence Handle1:STN:280:By2C2Mzit1I%3D Occurrence Handle1786059
P Liu SL Vonderfect MA Fisher GM McGuire H Jaeschke (1994) ArticleTitlePriming of phagocytes for reactive oxygen production during hepatic ischemia-reperfusion potentiates the susceptibility for endotoxin-induced liver injury Circ Shock 43 9–17 Occurrence Handle1:CAS:528:DyaK2cXmtVeiu74%3D Occurrence Handle7982273
E Nagel AM zu Vilsendorf M Bartels R Pichlmayr (1997) ArticleTitleAntioxidative vitamins in prevention of ischemia/reperfusion injury Int J Vit Nutr Res 67 298–306 Occurrence Handle1:CAS:528:DyaK2sXntFWmur0%3D
E Cadenas H Sies (1998) ArticleTitleThe lag phase Free Radic Res 28 601–9 Occurrence Handle1:CAS:528:DyaK1cXlvFegtLo%3D Occurrence Handle9736312
W Stahl H Sies (1997) ArticleTitleAntioxidant defense: vitamins E and C and carotenoids Diabetes Suppl 2 46 S14–8 Occurrence Handle1:CAS:528:DyaK2sXlvFKgtbo%3D
G Vendemiale I Grattagliano E Altomare (1999) ArticleTitleAn update on the of free radicals and antioxidant defense in human disease Int J Clin Lab Res 29 49–55 Occurrence Handle10.1007/s005990050063 Occurrence Handle1:CAS:528:DyaK1MXlsF2gtrk%3D Occurrence Handle10436261
RS McCuskey (1996) Hepatic microcirculation as a major determinant of hepatic function T Kamada T Shiga RS McCuskey (Eds) Tissue perfusion and organ function: ischemia/reperfusion injury Elsevier Science Amsterdam
B Halliwell Gutteridge J. Antioxidant (1999) defenses. In: Free radicals in biology and in medicine EditionNumber3rd ed Oxford University Press New York
L Packer (1991) ArticleTitleProtective role of vitamin E in biological systems Am J Clin Nutr 53 1050S–5S Occurrence Handle1:CAS:528:DyaK3MXltlClu7w%3D Occurrence Handle2012017
M McCall B Frei (1999) ArticleTitleCan antioxidant vitamins materially reduce oxidative damage in humans? Free Radic Biol Med 26 1034–53 Occurrence Handle10.1016/S0891-5849(98)00302-5 Occurrence Handle1:CAS:528:DyaK1MXislGktr0%3D Occurrence Handle10232849
D Giakoustidis G Papageorgiou S Iliadis N Kontos E Kostopoulou A Papachrestou et al. (2002) ArticleTitleIntramuscular administration of very high dose of alpha-tocopherol protects liver from severe ischemia/reperfusion injury World J Surg 26 872–7 Occurrence Handle10.1007/s00268-002-6271-2 Occurrence Handle11960213
InstitutionalAuthorNameCommittee on Care and Use of Laboratory Animals (1985) Guide for the care and use of laboratory animals Institute of Laboratory Animal Resources, National Research Council Washington, DC
NA Botsoglou DJ Fletouris GE Papageorgiou VN Vassilopoulos AJ Mantis AG Trakatelis (1994) ArticleTitleRapid, sensitive and specific thiobarbituric acid method for measuring lipid peroxidation in animal tissue, food and feedstuff samples J Agric Food Chem 42 1931–6 Occurrence Handle10.1021/jf00045a019 Occurrence Handle1:CAS:528:DyaK2cXlsFKjtrc%3D
JE Krawisz P Sharon WF Stenson (1984) ArticleTitleQuantitative assay for acute intestinal inflammation based on myeloperoxidase activity Gastroenterology 87 1344–50 Occurrence Handle1:CAS:528:DyaL2MXktVym Occurrence Handle6092199
MB Grisham LA Hernandez DN Granger (1986) ArticleTitleXanthine oxidase and neutrophil infiltration in intestinal ischemia Am J Physiol 251 G567–74 Occurrence Handle1:CAS:528:DyaL28Xmt1ersbY%3D Occurrence Handle3020994
J Arnaud I Fortis S Blachier D Kia A Favier (1991) ArticleTitleSimultaneous determination of retinol, α-tocopherol and β-carotene by isocratic high-performance liquid chromatography J Chromatogr 572 103–16 Occurrence Handle1:CAS:528:DyaK38Xhslyrsw%3D%3D Occurrence Handle1818046
S Suzuki LH Toledo-Pereyra FJ Rodriguez D Cejalvo (1993) ArticleTitleNeutrophil infiltration as an important factor in liver ischemia and reperfusion injury. Modulating effects of FK-506 and cyclosporine Transplantaion 55 1265–72 Occurrence Handle1:STN:280:ByyB1MnotlE%3D
RGD Steel JH Torrie (1980) Principles and procedures of statistics. A biometrical approach EditionNumber2nd ed McGraw-Hill New York
M Glanemann R Strenziok R Kuntze S Munchow N Dikopoulos F Lippek et al. (2004) ArticleTitleIschemic preconditioning and methylprednisolone both equally reduce hepatic ischemia/reperfusion injury Surgery 135 203–14 Occurrence Handle10.1016/j.surg.2003.08.011 Occurrence Handle14739856
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Giakoustidis, D., Papageorgiou, G., Iliadis, S. et al. The Protective Effect of α-Tocopherol and GdCl3 Against Hepatic Ischemia/Reperfusion Injury. Surg Today 36, 450–456 (2006). https://doi.org/10.1007/s00595-005-3162-9
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DOI: https://doi.org/10.1007/s00595-005-3162-9