Centrilobular endothelial cell injury by diquat in the selenium-deficient rat liver.
Low doses of diquat cause massive liver necrosis and death of selenium-deficient rats within a few hours. Protection against this injury by selenium correlates with the presence of selenoprotein P, an extracellular selenoprotein that associates with endothelial cells. Selenium-deficient rats were injected with diquat (10 mg/kg) and their livers were removed for light and electron microscopy at times up to 120 minutes after injection. Selenium-replete animals were studied before and 120 minutes after the same dose of diquat. With selenium deficiency, diquat caused injury to centrilobular endothelial cells. This injury was evident 20 minutes after diquat injection and progressed to cell loss at 60 minutes after diquat injection. At 120 minutes, endothelial cells were virtually absent from the centrilobular regions and hepatocytes in those areas were undergoing necrosis. Portal and midzonal areas remained normal in selenium-deficient livers, as did the entire liver lobule of selenium-replete rats. These findings indicate that the initial liver lesion in selenium-deficient rats given diquat is injury of the endothelial cells in the centrilobular region. After detachment of the endothelial cells, centrilobular hepatocytes undergo necrosis. We postulate that selenoprotein P protects the centrilobular endothelial cells against injury by oxidant molecules that result from diquat administration.
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
J B
JB
Atkinson
K E
KE
Hill
R F
RF
Burk
D000818:Animals; D004178:Diquat / Q000633:toxicity*; D004727:Endothelium / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D005979:Glutathione Peroxidase / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012643:Selenium / Q000172:deficiency* / Q000494:pharmacology; D051149:Selenoprotein P; D051140:Selenoproteins
D011506:Proteins; D051149:Selenoprotein P; D051140:Selenoproteins; D004178:Diquat; D005979:Glutathione Peroxidase; D012643:Selenium