title: Simultaneous proteosome inhibition and heat shock protein induction by bortezomib is beneficial in experimental pancreatitis.
abstract: The proteosome inhibitor bortezomib is used in the treatment of patients with multiple myeloma. Proteosomes are responsible for the degradation of I-kappaB, the inhibitory protein of transcription factor nuclear factor kappa B (Nf-kappaB). 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. 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 hourly s.c. injections of 100 microg/kg CCK-8. Group BP received 1 mg/kg bortezomib dissolved in p.s. 1 h 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. Bortezomib pre-treatment significantly reduced the pancreatic weight/body weight ratio, and improved the histology by decreasing the extent of vacuolization and infiltration. Bortezomib pre-treatment inhibited I-kappaBbeta degradation, and induced the synthesis of HSP72. 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-kappaB activation and induction of HSP synthesis.
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary. anna_szabolcs@yahoo.com
authors.forename: Annamária
authors.initials: A
authors.lastname: Szabolcs
authors.forename: György
authors.initials: G
authors.lastname: Biczó
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Rakonczay
authors.forename: László
authors.initials: L
authors.lastname: Tiszlavicz
authors.forename: Gabriella
authors.initials: G
authors.lastname: Halm
authors.forename: Tibor
authors.initials: T
authors.lastname: Wittmann
authors.forename: Tamás
authors.initials: T
authors.lastname: Takács
mesh_terms: D000818:Animals; D001897:Boronic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D000069286:Bortezomib; D006360:Heat-Shock Proteins / Q000378:metabolism*; D008297:Male; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001897:Boronic Acids; D006360:Heat-Shock Proteins; D009097:Multienzyme Complexes; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib