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.
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Authors | 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 |
Journal | American journal of physiology. Gastrointestinal and liver physiology
(Am J Physiol Gastrointest Liver Physiol)
Vol. 296
Issue 5
Pg. G1040-6
(May 2009)
ISSN: 0193-1857 [Print] United States |
PMID | 19282375
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- HIV Protease Inhibitors
- Inflammation Mediators
- Ceruletide
- Cytochromes c
- Amylases
- Trypsin
- Casp3 protein, rat
- Caspase 3
- Nelfinavir
- Ritonavir
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Topics |
- Amylases
(blood)
- Animals
- Apoptosis
(drug effects)
- Caspase 3
(metabolism)
- Ceruletide
- Cytochromes c
(metabolism)
- Disease Models, Animal
- Drug Therapy, Combination
- HIV Protease Inhibitors
(pharmacology)
- Inflammation Mediators
(blood)
- Male
- Membrane Potential, Mitochondrial
(drug effects)
- Mice
- Mice, Inbred C57BL
- Mitochondria
(drug effects, pathology)
- Necrosis
- Nelfinavir
(pharmacology)
- Pancreas
(drug effects, metabolism, pathology)
- Pancreatitis
(chemically induced, drug therapy, metabolism, pathology)
- Ritonavir
(pharmacology)
- Trypsin
(metabolism)
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