title: Melatonin reduces apoptosis and necrosis induced by ischemia/reperfusion injury of the pancreas.
abstract: The pancreas is highly susceptible to the oxidative stress induced by ischemia/reperfusion (IR) injury leading to the generation of acute pancreatitis. Melatonin has been shown to be useful in the prevention of the damage by ischemia-reperfusion in liver, brain, myocardium, gut and kidney. The aim of the study was to evaluate the cytoprotective properties of melatonin against injury induced by IR in pancreas. The obstruction of gastro-duodenal and inferior splenic arteries induced pancreatic IR in male Wistar rats. Melatonin was intraperitoneally administered before or/and after IR injury. The animals were killed at 24 and 48 hr after reperfusion and there were evaluated parameters of oxidative stress (lipoperoxides, superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione), glandular endocrine and exocrine function (lipase, amylase, insulin) and cell injury (apoptosis and necrosis). The IR induced a marked enhancement of oxidative stress and impaired pancreatic function. The histological analysis showed that IR induced acute pancreatitis with the accumulation of inflammatory infiltrate, disruption of tissue structure, cell necrosis and hemorrhage. Melatonin administration before or after pancreatic IR prevented all tissue markers of oxidative stress, biochemical and histological signs of apoptosis and necrosis, and restored glandular function. No histological signs of pancreatitis were observed 48 hr after reperfusion in 80% of the animals treated with melatonin, with only a mild edematous pancreatitis being observed in the remaining rats. Preventive or therapeutic administration of melatonin protected against the induction of oxidative stress and tissue injury, and restored cell function in experimental pancreatic IR in rats.
authors.affiliation: Department of General Surgery, Reina Sofia University Hospital, Cordoba, Spain.
authors.forename: Francisco C
authors.initials: FC
authors.lastname: Muñoz-Casares
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Padillo
authors.forename: Javier
authors.initials: J
authors.lastname: Briceño
authors.forename: Juan A
authors.initials: JA
authors.lastname: Collado
authors.forename: Juan R
authors.initials: JR
authors.lastname: Muñoz-Castañeda
authors.forename: Rosa
authors.initials: R
authors.lastname: Ortega
authors.forename: Adolfo
authors.initials: A
authors.lastname: Cruz
authors.forename: Isaac
authors.initials: I
authors.lastname: Túnez
authors.forename: Pedro
authors.initials: P
authors.lastname: Montilla
authors.forename: Carlos
authors.initials: C
authors.lastname: Pera
authors.forename: Jordi
authors.initials: J
authors.lastname: Muntané
mesh_terms: D000681:Amylases / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008049:Lipase / Q000097:blood; D015227:Lipid Peroxidation; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D009336:Necrosis / Q000517:prevention & control; D010179:Pancreas / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D010195:Pancreatitis / Q000503:physiopathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D007328:Insulin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D008049:Lipase; D000681:Amylases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione; D008550:Melatonin