Centrilobular endothelial cell injury by diquat in the selenium-deficient rat liver

Low doses of diquat cause massive liver necrosis and death of selenium-defi cient rats within a few hours. Protection against this injury by selenium c orrelates with the presence of selenoprotein P, an extracellular selenoprot ein that associates with endothelial cells. Selenium-deficient rats were in jected with diquat (10 mg/kg) and their livers were removed for light and e lectron microscopy at times up to 120 minutes after injection. Selenium-rep lete animals were studied before and 120 minutes after the same dose of diq uat. With selenium deficiency, diquat caused injury to centrilobular endoth elial cells. This injury was evident 20 minutes after diquat injection and progressed to cell loss at 60 minutes after diquat injection. At 120 minute s, endothelial cells were virtually absent from the centrilobular regions a nd hepatocytes in those areas were undergoing necrosis. Portal and midzonal areas remained normal in selenium-deficient livers, as did the entire live r lobule of selenium-replete rats. These findings indicate that the initial liver lesion in selenium-deficient rats given diquat is injury of the endo thelial cells in the centrilobular region. After detachment of the endothel ial cells, centrilobular hepatocytes undergo necrosis. We postulate that se lenoprotein P protects the centrilobular endothelial cells against injury b y oxidant molecules that result from diquat administration.