Simultaneous proteosome inhibition and heat shock protein induction by bortezomib is beneficial in experimental pancreatitis.
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.
Szabolcs
Annamária
A
First Department of Medicine, University of Szeged, Szeged, Hungary. anna_szabolcs@yahoo.com
Biczó
György
G
Rakonczay
Zoltán
Z
Tiszlavicz
László
L
Halm
Gabriella
G
Wittmann
Tibor
T
Takács
Tamás
T
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
D001897:Boronic Acids; D006360:Heat-Shock Proteins; D009097:Multienzyme Complexes; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib