Effects of rapamycin treatment on pancreatic fibrosis, cellular apoptosis and oxidative stress in experimental chronic pancreatitis model.

Abstract

PURPOSE:

Rapamycin reduces hepatic fibrosis by inhibiting hepatic stellate cell activation. The present study investigated whether rapamycin treatment could modify the degree of fibrosis, cellular apoptosis and oxidative stress (OS) in an experimental model of CP.

METHODS:

Fifty-five male, Sprague-Dawley rats weighing 200-400g were randomized into four groups. CP was induced by intraductal trinitrobenzene sulfonic acid (TNBS) infusion in group A (n = 15) and group B (n = 15). Group C (n = 15) received intraductal TNBS and was killed for histologic confirmation at four weeks. Group D (n = 10) received intraductal saline instead of TNBS. Group A and group D received oral rapamycin (2 mg/kg/d) for two weeks after CP was induced while group B received oral tap water instead of rapamycin. Blood and pancreatic tissue specimens were collected and oxidative stress parameters, fibrosis and cellular apoptosis were determined.

RESULTS:

Tissue and blood malondialdehyde (MDA) levels were significantly lower in rapamycin treated group compared to controls (p < 0.001). Superoxide dismutase (SOD) and glutathion peroxidase (GSH-Px) activities were also significantly higher in the active treatment group (p < 0.001 for both). Tissue and blood MDA, SOD, GSH-Px measurements was similar in rapamycin group and pancreatic cannulation group (p > 0.05). Histopathologic fibrosis scores were similar in rapamycin and control groups. Apoptotic cell counts tended to be lower in rapamycin treated animals.

CONCLUSIONS:

Administration of rapamycin alleviated OS and, in part, prevented apoptotic cell death in experimental CP, but did not reduce fibrosis.

• Authors: K Ozturk, I Tasci, M Yasar, C Akay, M Alcigir, S Vural, M R Mas, T Turker, K Saglam
• Journal: Acta gastro-enterologica Belgica (Acta Gastroenterol Belg) 2015 Jan-Mar Vol. 78 Issue 1 Pg. 3-7 ISSN: 1784-3227 [Print] Belgium
• PMID: 26118571 (Publication Type: Journal Article)
• Copyright: Copyright© Acta Gastro-Enterologica Belgica.

Chemical References

• Antibiotics, Antineoplastic
• Malondialdehyde
• Trinitrobenzenesulfonic Acid
• Glutathione Peroxidase
• Superoxide Dismutase
• Sirolimus

Topics

• Animals
• Antibiotics, Antineoplastic (pharmacology)
• Apoptosis (drug effects)
• Disease Models, Animal
• Fibrosis
• Glutathione Peroxidase (drug effects, metabolism)
• Male
• Malondialdehyde (metabolism)
• Oxidative Stress (drug effects)
• Pancreas (drug effects, metabolism, pathology)
• Pancreatitis, Chronic (chemically induced, metabolism)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Sirolimus (pharmacology)
• Superoxide Dismutase (drug effects, metabolism)
• Trinitrobenzenesulfonic Acid (toxicity)