Nelfinavir/ritonavir reduces acinar injury but not inflammation during mouse caerulein pancreatitis

Vijay P. Singh, Gary D. Bren, Alicia Algeciras-Schimnich, David Schnepple, Sarah Navina, Stacey A. Rizza, Rajinder K. Dawra, Ashok K. Saluja, Suresh T. Chari, Santhi S. Vege, Andrew D. Badley

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

There is no clinical treatment that reduces acinar injury during pancreatitis. Human immunodeficiency virus (HIV) protease inhibitors (PI), including nelfinavir (NFV) and ritonavir (RTV), may reduce the rate of pancreatitis in HIV-infected patients. Since permeability transition pore (PTPC)-mediated mitochondrial dysfunction occurs during pancreatitis, and we have shown that PI prevents PTPC opening, we studied its effects in a model of pancreatitis. The effect of NFV plus RTV (NFV/RTV) or vehicle on caerulein-induced pancreatitis in mice was compared by measuring changes in mitochondrial membrane potential in vitro and cytochrome c leakage in vivo. Histological and inflammatory makers were also compared. NFV/RTV improved DiOC6 retention in acini exposed to caerulein in vitro. In vivo NFV prevented cytosolic leakage of cytochrome c and reduced pancreatic acinar injury, active caspase-3 staining, TUNEL-positive acinar cells, and serum amylase (P < 0.05). Conversely, trypsin activity, serum cytokine levels, and pancreatic and lung inflammation were unaffected. NFV/RTV reduces pancreatic injury and acinar cell death in experimental mouse caerulein-induced pancreatitis but does not impact inflammation.

Original languageEnglish (US)
Pages (from-to)G1040-G1046
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume296
Issue number5
DOIs
StatePublished - May 2009

Keywords

  • Apoptosis
  • Necrosis
  • Permeability transition pore inhibition
  • Protease inhibitors

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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    Singh, V. P., Bren, G. D., Algeciras-Schimnich, A., Schnepple, D., Navina, S., Rizza, S. A., Dawra, R. K., Saluja, A. K., Chari, S. T., Vege, S. S., & Badley, A. D. (2009). Nelfinavir/ritonavir reduces acinar injury but not inflammation during mouse caerulein pancreatitis. American Journal of Physiology - Gastrointestinal and Liver Physiology, 296(5), G1040-G1046. https://doi.org/10.1152/ajpgi.90642.2008