Oxidative stress and inflammation in the pathogenesis of activated polyamine catabolism-induced acute pancreatitis.
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-kappaB 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-kappaB 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.
Merentie
M
M
Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland.
Uimari
A
A
Pietilä
M
M
Sinervirta
R
R
Keinänen
T A
TA
Vepsäläinen
J
J
Khomutov
A
A
Grigorenko
N
N
Herzig
K-H
KH
Jänne
J
J
Alhonen
L
L
D000123:Acetyltransferases / Q000378:metabolism; D000208:Acute Disease; D000818:Animals; D030801:Animals, Genetically Modified; D007249:Inflammation / Q000150:complications; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000502:physiology*; D010195:Pancreatitis / Q000209:etiology* / Q000473:pathology; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015032:Zinc; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D016753:Interleukin-10; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D009569:Nitric Oxide; D011073:Polyamines; D013096:Spermine; D014409:Tumor Necrosis Factor-alpha; D015032:Zinc; D000099228:Diamine N-Acetyltransferase