Poster Presenter

Proteosome Inhibition by Bortezomib is Beneficial in Experimental Pancreatitis
Annamária Szabolcs, György Biczó, Zoltán Rakonczay, László Tiszlavicz, Zsófia Csorba, Gabriella Halm, Peter Hegyi, Tamás Takács

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 transcription factor nuclear factor kappa B (Nf-κB). The heat shock protein (HSP) inducing effect of bortezomib is also documented. The Aim of our work was to test the anti-inflammatory effect of bortezomib in cholecystokinin-octapeptide (CCK-8)-induced acute pancreatitis. Methods: Male Wistar rats were divided into three groups (n=8 in each). Group P received an i.p. injection of physiological saline (p.s.) 60 min. before the induction of acute pancreatitis by three s.c. injections of 100µg/kg CCK-8. Group BP received 1 mg/kg bortezomib dissolves in p.s. one hour previous to pancreatitis induction. Group C was treated with the vehicle (p.s.). Animals were exsanguinated 4 h after the last injection of CCK-8. Results: Bortezomib pre-treatment significantly reduced the pw/bw ratio, and improved the histology by decreasing the extent of vacuolization and infiltration. Bortezomib pre-treatment inhibited I-κBβ degradation, 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-κB activation and induction of HSP synthesis.