Cytoprotection by metallothionein against gastroduodenal mucosal injury caused by ethanol in mice

Metallothionein (MT) is a small, cysteine-rich protein that can act as a fr ee radical scavenger at least in vitro. To test the hypothesis that MT part icipates in gastroduodenal cytoprotection, we studied sensitivity to gastro duodenal mucosal injury caused by ethanol in MT-null mice that have null mu tations in MT-I and MT-II genes. MT-null mice and wild-type mice were orall y treated with ethanol (60% or 99.5%, 0.2 ml/mouse). The macroscopic gastri c lesion indices were significantly higher in MT-null mice than in wild-typ e mice 90 minutes after ethanol treatment. Histopathological examination in ethanol-treated MT-null mice showed vacuolar degeneration, necrosis of the epithelial cells, and hemorrhage throughout the tunica mucosa. Moreover, t he duodenum also showed morphologic changes, including marked degeneration and coagulative necrosis of the entire villi, desquamation of the degenerat ed epithelial cells, and hemorrhage. In contrast, histopathologic changes w ere less prominent in the wild-type mice treated with ethanol. MT was not d etected either in the stomach or duodenum of Mi-null mice, whereas gastric and duodenal zinc contents were not significantly different between MT-null mice and wild-type mice. These results provide direct evidence that intrin sic MT plays a cytoprotective role in gastroduodenal mucosal injury caused by ethanol.