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- W2000657463 abstract "The proteosome inhibitor bortezomib is used in the treatment of patients with myeloma multiplex. Proteosomes are responsible for the degradation of I-κB, the inhibitory protein of the inflammatory transcription factor nuclear factor kappa B (Nf-κB). The heat shock protein (HSP) inducing effect of bortezomib is also documented. The role of Nf-κB and HSP72 in the development of acute pancreatitis is well known. The Aim of our work was to test the anti-inflammatory effect of bortezomib in CCK-8-induced acute pancreatitis. Methods: Male Wistar rats weighing 230–250g were divided into three groups (n=8 in each). Rats in group P received an i.p. injection of physiological saline (p.s.) 60min. before the induction of acute pancreatitis by three hourly s.c. injections of 100µg/kg CCK-8. Group BP received an i.p. injection of 1mg/kg bortezomib dissolved in p.s. one hour previous to pancreatitis induction. The control group (C) was injected with p.s. instead of bortezomib and CCK-8. Animals were exsanguinated 4h after the last injection of CCK-8. Results: Serum amylase level and pancreatic weight/body weight (pw/bw) ratio was elevated in the animals in group P and BP, and histology confirmed the development of pancreatitis (pw/bw: C:4,3±0,1; P:8,4±0,5; BP:7,2±0,4; p<0,001 P vs. C)(amylase: C:1449±83; P:12599±1159; BP:13278±1486; p<0,001 P vs. C)(totale damage: C:0,25±0,16; P:3,63±0,38 BP:2,38±0,38; p=0,001 P vs. C) Bortezomib pre-treatment significantly reduced the pw/bw ratio (p=0,039 BP vs. P), and improved the histology of pancreatitis (p=0,012). Western blot analysis of the pancreas revealed the degradation of I-κBβ in group P versus group C, whereas HSP72 was not detectable these groups. Bortezomib pre-treatment inhibited I-κBβ degradation (I-κBβ: C:6339±1294; P:2168±471; BP:9891±1257; p=0,024 P vs. C; p=0,001; BP vs. P), and induced the synthesis of HSP72. Conclusion: The results confirmed the anti-inflammatory effect of bortezomib in acute experimental pancreatitis. This effect of the drug is presumably mediated by the inhibition of Nf-κ B degradation." @default.
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- W2000657463 date "2008-05-01" @default.
- W2000657463 modified "2023-10-16" @default.
- W2000657463 title "Beneficial effect of bortezomib pre-treatment on cholecystokinin-octapeptide-(CCK-8)-induced experimental pancreatitis" @default.
- W2000657463 doi "https://doi.org/10.1055/s-2008-1079701" @default.
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