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

被引:30
作者
Merentie, M.
Uimari, A.
Pietila, M.
Sinervirta, R.
Keinanen, T. A.
Vepsalainen, J.
Khomutov, A.
Grigorenko, N.
Herzig, K.-H.
Janne, J.
Alhonen, L.
机构
[1] Univ Kuopio, AI Virtanen Inst Mol Sci, Dept Biotechnol & Mol Med, FI-70211 Kuopio, Finland
[2] Univ Kuopio, Dept Chem, FIN-70211 Kuopio, Finland
[3] Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow, Russia
[4] Kuopio Univ Hosp, Dept Internal Med, SF-70210 Kuopio, Finland
关键词
spermidine/spermine N-1-acetyltransferase; inflammatory cytokines; lipid peroxidation; superoxide dismutase; catalase; glutathione;
D O I
10.1007/s00726-007-0522-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (Me(2)Spm) 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 Me(2)Spm pretreatment. Glutathione level and catalase activity changed transiently, and the effect of Me(2)Spm was clear at 24 h. Serum inflammatory cytokine levels increased already at 4 h whereas NF-kB was distinctly activated only at 24 h. Me(2)Spm prevented the increase in TNF-alpha and IL-6 while it had no effect on NF-kB 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.
引用
收藏
页码:323 / 330
页数:8
相关论文
共 25 条
[1]  
AEBI H, 1984, METHOD ENZYMOL, V105, P121
[2]   Activation of polyamine catabolism in transgenic rats induces acute pancreatitis [J].
Alhonen, L ;
Parkkinen, JJ ;
Keinänen, T ;
Sinervirta, R ;
Herzig, KH ;
Jänne, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (15) :8290-8295
[3]  
Bernacki RJ, 1995, CLIN CANCER RES, V1, P847
[4]   Pathophysiology of acute pancreatitis [J].
Bhatia, M ;
Wong, FL ;
Cao, Y ;
Lau, HY ;
Huang, J ;
Puneet, P ;
Chevali, L .
PANCREATOLOGY, 2005, 5 (2-3) :132-144
[5]   ACCURATE TRANSCRIPTION INITIATION BY RNA POLYMERASE-II IN A SOLUBLE EXTRACT FROM ISOLATED MAMMALIAN NUCLEI [J].
DIGNAM, JD ;
LEBOVITZ, RM ;
ROEDER, RG .
NUCLEIC ACIDS RESEARCH, 1983, 11 (05) :1475-1489
[6]   Reactive oxygen intermediates in TNF signaling [J].
Garg, AK ;
Aggarwal, BB .
MOLECULAR IMMUNOLOGY, 2002, 39 (09) :509-517
[7]  
Grigorenko N. A., 2005, Bioorganicheskaya Khimiya, V31, P200
[8]   Spermine differentially regulates the production of interleukin-12 p40 and interleukin-10 and suppresses the release of the T helper 1 cytokine interferon-γ [J].
Haskó, G ;
Kuhel, DG ;
Marton, A ;
Nemeth, ZH ;
Deitch, EA ;
Szabó, C .
SHOCK, 2000, 14 (02) :144-149
[9]   Polyamines as a defense mechanism against lipoperoxidation in Trypanosoma cruzi [J].
Hernández, SM ;
Sánchez, MS ;
de Tarlovsky, MNS .
ACTA TROPICA, 2006, 98 (01) :94-102
[10]   Activated polyamine catabolism in acute pancreatitis -: α-methylated polyamine analogues prevent trypsinogen activation and pancreatitis-associated mortality [J].
Hyvönen, MT ;
Herzig, KH ;
Sinervirta, R ;
Albrecht, E ;
Nordback, I ;
Sand, J ;
Keinänen, TA ;
Vepsäläinen, J ;
Grigorenko, N ;
Khomutov, AR ;
Krüger, B ;
Jänne, J ;
Alhonen, L .
AMERICAN JOURNAL OF PATHOLOGY, 2006, 168 (01) :115-122