Pancreatic fibrosis in rats and its response to antioxidant treatment.
BACKGROUND
Oxidative stress plays a role in the development of pancreatic fibrosis.


OBJECTIVE
In the present study, we hypothesized that the administration of an antioxidant complex could ameliorate cerulein and cyclosporin A pancreatic fibrosis, assessed by changes in oxidative stress and a histopathological study in an experimental rat model.


METHODS
Four groups of ten rats each. In Group A, the rats served as controls and were treated with intraperitoneal saline solution. In Group B, six courses of cerulein pancreatitis were induced at weekly intervals. In Group C, the rats received cyclosporin A the day before and the day on which pancreatitis was induced in Group B. In Group D, the rats were treated as in Group C but also received antioxidants. All rats were sacrificed at the seventh week.


METHODS
The presence of fibrosis was evaluated according to a scoring system. Glutathione peroxidase was utilized as an indicator of oxidative stress and total antioxidant status as an indicator of total antioxidant tissue capacity.


RESULTS
The rats in Groups B and C showed more pancreatic fibrosis than those in Groups A and D (90%, 70%, 0%, and 20%, respectively). The glutathione peroxidase increased in Group B (455+/-196 mU/g protein) and Group C (243+/-206 mU/g protein) with respect to those in Group A (137+/-80 mU/g protein) and Group D (135+/-105 mU/g protein). Total antioxidant status was significantly higher in Groups B (1.41+/-0.96 mmol/g protein) and D (1.28+/-0.09 mmol/g protein) with respect to Groups A (0.10+/-0.06 mmol/g protein) and C (0.15+/-0.09 mmoL/g protein).


CONCLUSIONS
The administration of cerulein and cyclosporin A caused fibrosis, whereas antioxidant administration showed preventive effects regarding cerulein and cyclosporin A-induced pancreatic fibrosis.
de Las Heras-Castaño
Gonzalo
G
Departament of Gastroenterology, Hospital Universitario Marqués de Valdecilla, Santander, Spain. gherasc@ono.com
García-Unzueta
María Teresa
MT
Domínguez-Diez
Agustín
A
Fernández-González
María Dolores
MD
García-de la Paz
Ana María
AM
Mayorga-Fernández
Marta
M
Fernández-Fernández
Fidel
F
D000818:Animals; D000975:Antioxidants / Q000032:analysis / Q000627:therapeutic use*; D002108:Ceruletide; D002908:Chronic Disease; D016572:Cyclosporine; D005355:Fibrosis; D005979:Glutathione Peroxidase / Q000032:analysis; D008297:Male; D018384:Oxidative Stress; D010179:Pancreas / Q000201:enzymology / Q000473:pathology*; D010195:Pancreatitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D016572:Cyclosporine; D002108:Ceruletide; D005979:Glutathione Peroxidase