Melatonin, a pineal indoleamine, protects the pancreas against acute damage; however, the involvement of the pineal gland in the pancreatoprotective action of
melatonin is unknown. The primary aim of this study was to determine the effects of
pinealectomy on the course of acute
caerulein-induced
pancreatitis (AP) in rats. AP was induced by a
subcutaneous infusion of
caerulein (25 μg/kg) into pinealectomized or
sham-operated animals.
Melatonin (5 or 25 mg/kg) was given via intraperitoneal (ip) injection 30 min prior to the induction of AP. The pancreatic content of the lipid peroxidation products
malondialdehyde and
4-hydroxynonenal (MDA + 4HNE) and the activity of an antioxidative
enzyme,
glutathione peroxidase (GSH-Px), were measured in each group of rats.
Melatonin blood levels were measured by radioimmunoassay (RIA). In the
sham-operated rats, AP was confirmed with histological examination and manifested as pancreatic
edema and an increase in the blood
lipase level (by 1,500%). In addition, the pancreatic content of MDA+ 4HNE was increased by 200%, and pancreatic
glutathione peroxydase (GSH-Px) activity was reduced by 40%.
Pinealectomy significantly aggravated the histological manifestations of AP, reduced the GSH-Px activity and markedly augmented the levels of MDA+ 4HNE in the pancreas of rats with or without AP as compared to
sham-operated animals.
Melatonin was undetectable in the blood of the pinealectomized rats with or without AP. Treatment with
melatonin (25 mg/kg, ip) prevented the development of AP in the
sham-operated rats and significantly reduced pancreatic
inflammation in the animals previously subjected to
pinealectomy. In conclusion, pineal
melatonin contributes to the pancreatic protection through the activation of the antioxidative defense mechanism in pancreatic tissue as well as its direct
antioxidant effects.