Increased pancreatic metallothionein and glutathione levels: protecting against cerulein- and taurocholate-induced acute pancreatitis in rats.

Recent findings have suggested that oxygen-derived free radicals play an important role in the development and progression of acute pancreatitis. Therefore, the present study was designed to investigate whether metallothionein, a free radical scavenger, can protect against acute pancreatitis. Rats were injected intraperitoneally with zinc, followed by either an infusion of cerulein at 10 micrograms/kg for 4 h or a retrograde injection with 100 microliters/100 g body weight of 5% sodium taurocholate into the pancreaticobiliary duct, in order to induce acute pancreatitis. Zn administration significantly increased the levels of both metallothionein and reduced glutathione in the pancreas; the metallothionein levels reached a peak of 83-fold of normal levels after 24 h. The indications of acute pancreatitis, as well as the mortality, were improved by Zn treatment before the onset of acute pancreatitis. Immunohistochemical studies showed that metallothionein accumulated in the acini of the pancreas in the Zn-treated groups, and with strong staining around the periphery of the vacuoles in the group treated with both Zn and cerulein. These findings suggested that Zn increased both metallothionein and glutathione levels in the pancreas and exerted a beneficial effect against ceruleinor taurocholate-induced acute pancreatitis in rats.