Therapeutic administration of orlistat, rosiglitazone, or the chemokine receptor antagonist RS102895 fails to improve the severity of acute pancreatitis in obese mice.
Pancreas
; 43(6): 903-8, 2014 Aug.
Article
en En
| MEDLINE
| ID: mdl-24632545
OBJECTIVE: Currently, there is no therapy for severe acute pancreatitis (AP) except for supportive care. The lipase inhibitor orlistat, the peroxisome proliferator-activated receptor γ agonist rosiglitazone, and the chemokine receptor 2 antagonists attenuate the severity of AP in rodents if administered before or at the time of induction of pancreatitis. However, it is unknown whether these treatments are effective if administered therapeutically after induction of pancreatitis. METHODS: Male C57BL6 mice with diet-induced obesity received 2 injections of mrIL-12 (150 ng per mouse) and mrIL-18 (750 ng per mouse) intraperitoneally at 24-hour intervals. The mice were injected 2, 24, and 48 hours after the second injection of IL-12 + IL-18 with orlistat (2 mg per mouse), rosiglitazone (0.4 mg per mouse), RS102895 (0.3 mg per mouse), or vehicle (20 µL of DMSO and 80 µL of canola oil) and euthanized after 72 hours. RESULTS: Orlistat decreased intra-abdominal fat necrosis compared with vehicle (P < 0.05). However, none of the drug treatments produced significant decreases in pancreatic edema, acinar necrosis, or intrapancreatic fat necrosis. CONCLUSIONS: Drugs previously shown to improve the severity of AP when given before or at the time of induction of pancreatitis failed to do so when administered therapeutically in the IL-12 + IL-18 model.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pancreatitis
/
Piperidinas
/
Tiazolidinedionas
/
Benzoxazinas
/
Lactonas
/
Obesidad
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Pancreas
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2014
Tipo del documento:
Article
Pais de publicación:
Estados Unidos