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Oxidative stress and inflammation in the pathogenesis of activated polyamine catabolism-induced acute pancreatitis

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Summary.

The markers of oxidative stress and inflammation were studied in acute pancreatitis in transgenic rats exhibiting activated polyamine catabolism. In addition, the effect of bismethylspermine (Me2Spm) pretreatment, preventing pancreatitis in this model, on these mediators was investigated. Lipid peroxidation was increased at 6 and 24 h after induction of pancreatitis. These changes as well as the markedly decreased superoxide dismutase activity at 24 h were abolished by Me2Spm pretreatment. Glutathione level and catalase activity changed transiently, and the effect of Me2Spm was clear at 24 h. Serum inflammatory cytokine levels increased already at 4 h whereas NF-κB was distinctly activated only at 24 h. Me2Spm prevented the increase in TNF-α and IL-6 while it had no effect on NF-κB activation. These results show that typical inflammatory and, to a lesser degree, some oxidative stress mediators are involved and beneficially affected by the disease-ameliorating polyamine analogue in our pancreatitis model.

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Abbreviations

AEBSF:

4-(2-aminoethyl)benzenesulfonyl fluoride

ELISA:

enzyme-linked immunosorbent assay

EMSA:

electrophoretic mobility shift assay

GSH:

reduced glutathione

GSSH:

oxidized glutathione

HRP:

horse radish peroxidase

IκB-α:

inhibitor-κBα

IL-1β:

interleukin-1β

IL-6:

interleukin-6

IL-10:

interleukin-10

LPO:

lipid hydroperoxide

NO:

nitric oxide

MDL72527:

N 1,N 2-bis(2,3-butanediyl)-1,4-butanediamine

Me2Spm:

bismethylspermine

NF-κB:

nuclear factor-κB

PAO:

polyamine oxidase

PMSF:

phenylmethanesulfonyl fluoride

SOD:

superoxide dismutase

SSAT:

spermidine/spermine-N1-acetyltransferase

TNF-α:

tumor necrosis factor-α

References

  • H Aebi (1984) ArticleTitleCatalase in vitro Methods Enzymol 105 121–126 Occurrence Handle6727660 Occurrence Handle1:CAS:528:DyaL2cXltVKis7s%3D Occurrence Handle10.1016/S0076-6879(84)05016-3

    Article  PubMed  CAS  Google Scholar 

  • L Alhonen JJ Parkkinen T Keinänen R Sinervirta KH Herzig J Jänne (2000) ArticleTitleActivation of polyamine catabolism in transgenic rats induces acute pancreatitis Proc Natl Acad Sci USA 97 8290–8295 Occurrence Handle10880565 Occurrence Handle10.1073/pnas.140122097 Occurrence Handle1:CAS:528:DC%2BD3cXlt1GgtL4%3D

    Article  PubMed  CAS  Google Scholar 

  • RJ Bernacki EJ Oberman KE Seweryniak A Atwood RJ Bergeron CW Porter (1995) ArticleTitlePreclinical antitumor efficacy of the polyamine analogue N1,N11-diethylnorspermine administered by multiple injections or continuous infusion Clin Cancer Res 1 847–857 Occurrence Handle9816054 Occurrence Handle1:CAS:528:DyaK2MXnsVeqsL4%3D

    PubMed  CAS  Google Scholar 

  • M Bhatia FL Wong Y Cao HY Lau J Huang P Puneet L Chevali (2005) ArticleTitlePathophysiology of acute pancreatitis Pancreatology 5 132–144 Occurrence Handle15849484 Occurrence Handle10.1159/000085265

    Article  PubMed  Google Scholar 

  • JD Dignam RM Lebovitz RG Roeder (1983) ArticleTitleAccurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei Nucleic Acids Res 11 1475–1489 Occurrence Handle6828386 Occurrence Handle10.1093/nar/11.5.1475 Occurrence Handle1:CAS:528:DyaL3sXhslCit74%3D

    Article  PubMed  CAS  Google Scholar 

  • AK Garg BB Aggarwal (2002) ArticleTitleReactive oxygen intermediates in TNF signaling Mol Immunol 39 509–517 Occurrence Handle12431383 Occurrence Handle10.1016/S0161-5890(02)00207-9 Occurrence Handle1:CAS:528:DC%2BD38XosFWqsbk%3D

    Article  PubMed  CAS  Google Scholar 

  • NA Grigorenko J Vepsäläinen A Järvinen TA Keinänen L Alhonen J Jänne AR Khomutov (2005) ArticleTitleNovel syntheses of α-methyl- and α,α’-dimethylspermine Bioorgan Khim (Moscow) 31 200–205 Occurrence Handle1:STN:280:DC%2BD2M3ltVGgsA%3D%3D

    CAS  Google Scholar 

  • G Hasko DG Kuhel A Marton ZH Nemeth EA Deitch C Szabo (2000) ArticleTitleSpermine differentially regulates the production of interleukin-12 p40 and interleukin-10 and suppresses the release of the T helper 1 cytokine interferon-gamma Shock 14 144–149 Occurrence Handle10947158 Occurrence Handle1:STN:280:DC%2BD3M%2FovFymug%3D%3D Occurrence Handle10.1097/00024382-200014020-00012

    Article  PubMed  CAS  Google Scholar 

  • SM Hernandez MS Sanchez MN de Tarlovsky (2006) ArticleTitlePolyamines as a defense mechanism against lipoperoxidation in Trypanosoma cruzi Acta Trop 98 94–102 Occurrence Handle16574050 Occurrence Handle10.1016/j.actatropica.2006.02.005 Occurrence Handle1:CAS:528:DC%2BD28XjsFOnsb4%3D

    Article  PubMed  CAS  Google Scholar 

  • MT Hyvönen KH Herzig R Sinervirta E Albrecht I Nordback J Sand TA Keinänen J Vepsäläinen N Grigorenko AR Khomutov B Krüger J Jänne L Alhonen (2006) ArticleTitleActivated polyamine catabolism in acute pancreatitis: alpha-methylated polyamine analogues prevent trypsinogen activation and pancreatitis-associated mortality Am J Pathol 168 115–122 Occurrence Handle16400014 Occurrence Handle10.2353/ajpath.2006.050518 Occurrence Handle1:CAS:528:DC%2BD28XhtVKksLc%3D

    Article  PubMed  CAS  Google Scholar 

  • Hyvönen MT, Merentie M, Uimari A, Keinänen TA, Jänne J, Alhonen L (2007) Mechanisms of polyamine catabolism-induced acute pancreatitis. Biochem Soc Trans (in press)

  • T Hyvönen TA Keinänen AR Khomutov RM Khomutov TO Eloranta (1992) ArticleTitleMonitoring of the uptake and metabolism of aminooxy analogues of polyamines in cultured cells by high-performance liquid chromatography J Chromatogr 574 17–21 Occurrence Handle1629283 Occurrence Handle10.1016/0378-4347(92)80093-6

    Article  PubMed  Google Scholar 

  • E Lovaas G Carlin (1991) ArticleTitleSpermine: an anti-oxidant and anti-inflammatory agent Free Radic Biol Med 11 455–461 Occurrence Handle1663062 Occurrence Handle10.1016/0891-5849(91)90061-7 Occurrence Handle1:STN:280:DyaK387itVGrsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • B Matkovics V Kecskemeti SI Varga Z Novak Z Kertesz (1993) ArticleTitleAntioxidant properties of di- and polyamines Comp Biochem Physiol 104B 475–479 Occurrence Handle1:CAS:528:DyaK3sXit1Glsbk%3D

    CAS  Google Scholar 

  • J Norman (1998) ArticleTitleThe role of cytokines in the pathogenesis of acute pancreatitis Am J Surg 175 76–83 Occurrence Handle9445247 Occurrence Handle10.1016/S0002-9610(97)00240-7 Occurrence Handle1:CAS:528:DyaK1cXntVGmtQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • J Pereda L Sabater L Aparisi J Escobar J Sandoval J Vina G Lopez-Rodas J Sastre (2006) ArticleTitleInteraction between cytokines and oxidative stress in acute pancreatitis Curr Med Chem 13 2775–2787 Occurrence Handle17073628 Occurrence Handle10.2174/092986706778522011 Occurrence Handle1:CAS:528:DC%2BD28XhtVamsrnI

    Article  PubMed  CAS  Google Scholar 

  • FJ Perez-Cano A Franch C Castellote M Castell (2003) ArticleTitleImmunomodulatory action of spermine and spermidine on NR8383 macrophage line in various culture conditions Cell Immunol 226 86–94 Occurrence Handle14962496 Occurrence Handle10.1016/j.cellimm.2003.09.009 Occurrence Handle1:CAS:528:DC%2BD2cXhtV2htLk%3D

    Article  PubMed  CAS  Google Scholar 

  • TL Räsänen L Alhonen R Sinervirta T Keinänen KH Herzig S Suppola AR Khomutov J Vepsäläinen J Jänne (2002) ArticleTitleA polyamine analogue prevents acute pancreatitis and restores early liver regeneration in transgenic rats with activated polyamine catabolism J Biol Chem 277 39867–39872 Occurrence Handle12181316 Occurrence Handle10.1074/jbc.M205967200 Occurrence Handle1:CAS:528:DC%2BD38XnvVehs78%3D

    Article  PubMed  CAS  Google Scholar 

  • B Rau B Poch F Gansauge A Bauer AK Nussler T Nevalainen MH Schoenberg HG Beger (2000) ArticleTitlePathophysiologic role of oxygen free radicals in acute pancreatitis: initiating event or mediator of tissue damage? Ann Surg 231 352–360 Occurrence Handle10714628 Occurrence Handle10.1097/00000658-200003000-00008 Occurrence Handle1:STN:280:DC%2BD3c7nslWisg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • H Sanfey GB Bulkley JL Cameron (1985) ArticleTitleThe pathogenesis of acute pancreatitis. The source and role of oxygen-derived free radicals in three different experimental models Ann Surg 201 633–639 Occurrence Handle2581519 Occurrence Handle10.1097/00000658-198505000-00013 Occurrence Handle1:CAS:528:DyaL2MXks12hsbY%3D

    Article  PubMed  CAS  Google Scholar 

  • HU Schulz C Niederau H Klonowski-Stumpe W Halangk R Luthen H Lippert (1999) ArticleTitleOxidative stress in acute pancreatitis Hepatogastroenterology 46 2736–2750 Occurrence Handle10576339 Occurrence Handle1:CAS:528:DyaK1MXnvFSksb0%3D

    PubMed  CAS  Google Scholar 

  • N Seiler CL Atanassov (1994) ArticleTitleThe natural polyamines and the immune system Progr Drug Res 43 87–141 Occurrence Handle1:CAS:528:DyaK2MXjt1Gjtr4%3D

    CAS  Google Scholar 

  • AP Senft TP Dalton HG Shertzer (2000) ArticleTitleDetermining glutathione and glutathione disulfide using the fluorescence probe o-phthalaldehyde Anal Biochem 280 80–86 Occurrence Handle10805524 Occurrence Handle10.1006/abio.2000.4498 Occurrence Handle1:CAS:528:DC%2BD3cXit1Gjs7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • C Szabó GJ Southan C Thiemermann JR Vane (1994) ArticleTitleThe mechanism of the inhibitory effect of polyamines on the induction of nitric oxide synthase: role of aldehyde metabolites Br J Pharmacol 113 757–766 Occurrence Handle7532082

    PubMed  Google Scholar 

  • M Zhang T Caragine H Wang PS Cohen G Botchkina K Soda M Bianchi P Ulrich A Cerami B Sherry KJ Tracey (1997) ArticleTitleSpermine inhibits proinflammatory cytokine synthesis in human mononuclear cells: a counterregulatory mechanism that restrains the immune response J Exp Med 185 1759–1768 Occurrence Handle9151701 Occurrence Handle10.1084/jem.185.10.1759 Occurrence Handle1:CAS:528:DyaK2sXjsFeis7k%3D

    Article  PubMed  CAS  Google Scholar 

  • M Zhang H Wang KJ Tracey (2000) ArticleTitleRegulation of macrophage activation and inflammation by spermine: a new chapter in an old story Crit Care Med 28 IssueIDSuppl 4 N60–N66 Occurrence Handle10807317 Occurrence Handle10.1097/00003246-200004001-00007 Occurrence Handle1:STN:280:DC%2BD3c3msFGqtQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland

    M. Merentie, A. Uimari, M. Pietilä, R. Sinervirta, T. A. Keinänen, K.-H. Herzig, J. Jänne & L. Alhonen

  2. Department of Chemistry, University of Kuopio, Kuopio, Finland

    J. Vepsäläinen

  3. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia

    A. Khomutov & N. Grigorenko

  4. Department of Internal Medicine, Kuopio University Hospital, Kuopio, Finland

    K.-H. Herzig

Authors
  1. M. Merentie
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  2. A. Uimari
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  3. M. Pietilä
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  4. R. Sinervirta
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  5. T. A. Keinänen
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  6. J. Vepsäläinen
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  7. A. Khomutov
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  11. L. Alhonen
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Merentie, M., Uimari, A., Pietilä, M. et al. Oxidative stress and inflammation in the pathogenesis of activated polyamine catabolism-induced acute pancreatitis. Amino Acids 33, 323–330 (2007). https://doi.org/10.1007/s00726-007-0522-3

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  • DOI: https://doi.org/10.1007/s00726-007-0522-3

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