Simultaneous proteosome inhibition and heat shock protein induction by bortezomib is beneficial in experimental pancreatitis

Annamária Szabolcs, György Biczó, Zoltán Rakonczay, László Tiszlavicz, Gabriella Halm, Tibor Wittmann, Tamás Takács

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The proteosome inhibitor bortezomib is used in the treatment of patients with multiple myeloma. 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. 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 μg/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-κBβ 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-κB activation and induction of HSP synthesis.

Original languageEnglish
Pages (from-to)270-274
Number of pages5
JournalEuropean Journal of Pharmacology
Volume616
Issue number1-3
DOIs
Publication statusPublished - Aug 15 2009

Keywords

  • Acute pancreatitis
  • Bortezomib
  • CCK-8
  • HSP
  • I-κB
  • NF-κB

ASJC Scopus subject areas

  • Pharmacology

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