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Oxidative stress and inflammation in the pathogenesis of activated polyamine catabolism-induced acute pancreatitis
Authors:M. Merentie  A. Uimari  M. Pietilä  R. Sinervirta  T. A. Keinänen  J. Vepsäläinen  A. Khomutov  N. Grigorenko  K.-H. Herzig  J. Jänne  L. Alhonen
Affiliation:(1) Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland;(2) Department of Chemistry, University of Kuopio, Kuopio, Finland;(3) Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia;(4) Department of Internal Medicine, Kuopio University Hospital, Kuopio, Finland
Abstract: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.
Keywords:: Spermidine/spermine N1-acetyltransferase –   Inflammatory cytokines –   Lipid peroxidation –   Superoxide dismutase –   Catalase –   Glutathione
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