The circadian rhythm of melatonin modulates the severity of caerulein‐induced pancreatitis in the rat

Abstract

Melatonin, an antioxidant, protects the pancreas against acute inflammation but, although this indole is released mainly at night, no study has been undertaken to determine circadian changes of plasma melatonin levels and the severity of acute pancreatitis. The aims of this study were: (a) to compare the severity of caerulein-induced pancreatitis (CIP) produced in the rat during the day and at the night, and (b) to assess the changes of plasma melatonin level and the activity of an antioxidative enzyme; superoxide dismutase (SOD), in the pancreas subjected to CIP during the day time and at night without or with administration of exogenous melatonin or its precursor; l-tryptophan. Rats were kept in 12 hr light/dark cycle. CIP was induced by subcutaneous infusion of caerulein (5 microg/kg/hr for 5 hr). Melatonin (5 or 25 mg/kg) or l-tryptophan (50 or 250 mg/kg) was given intraperitoneally 30 min prior to the start of CIP. CIP induced during the day time was confirmed by histological examination and manifested by pancreatic edema, and rises of amylase and lipase plasma activities (by 400 and 500%, respectively), whereas pancreatic SOD, pancreatic blood flow (PBF) and oxygen consumption by pancreatic tissue (VO(2)) were decreased by 70, 40 and 45%, respectively, as compared with the appropriate controls. All morphological and biochemical parameters of CIP induced at night were significantly less severe, compared with those recorded during the light phase. Plasma melatonin immunoreactivity was significantly higher during the night, than during the day, especially following administration of melatonin or its precursor, which reversed all manifestations of CIP. In conclusion, a circadian rhythm modulates the severity of CIP with a decrease of pancreatitis severity during the night compared with that at the day time and this may be due to the increased plasma level of melatonin and higher activity of SOD in the pancreas.

Melatonin Modulates the Severity of Taurocholate-Induced Acute Pancreatitis in the Rat

“…No statistically significant difference was observed between group 1 and group 3 in terms of amylase levels. Despite one study reporting that melatonin has no effect on serum amylase levels [42], our results support the other reports that showed a decline in serum amylase levels following melatonin treatment [31,43,44].…”

The effects of melatonin on the oxidants and antioxidants in the pancreatic tissue during the aging process

“…Yapılan çalışmalar-da genellikle yaşlanma ile birlikte dokulardaki serbest radikal düzeylerinin arttığı bildirilmektedir [5][6][7]. Hem ekzokrin, hem de endokrin salgı yapan bir bez olan pankreasla ilgili yapılan çalışmalarda, yaş ilerledikçe serbest radikal düzeyinin arttığı, antioksidan kapasitenin ise düştüğü bildirilmiştir [8].…”

Effect of melatonin on the severity of L-arginine-induced experimental acute pancreatitis in rats

“…Melatonin decreased the edema in the pancreas and stomach, and also the extent of lipid peroxidation in the pancreas. Jaworek et al [30] . demonstrated that even the circadian changes in physiological levels of melatonin reduce the severity of experimental pancreatitis [30] .…”

“…Jaworek et al [30] . demonstrated that even the circadian changes in physiological levels of melatonin reduce the severity of experimental pancreatitis [30] . L-Arg-induced pancreatitis is an experimental model of severe necrotizing acute pancreatitis.…”