Association between endothelial cell proliferation and pathologic changes in experimental alcoholic liver disease.
We evaluated the role of endothelial cell (EC) proliferation in experimental alcoholic liver disease (ALD) using different dietary models of ALD. Rats were divided into treatment groups to receive ethanol with either corn oil (CO + E), fish oil (FO + E), saturated fat (SF + E), and corn oil with a novel quinone derivative (E3330) and cimetidine. All ethanol-fed rats in the different groups were pair-fed with dextrose replacing the ethanol-derived calories. All ethanol-fed groups and their controls were fed for periods ranging from 1 to 4 weeks. For each animal, immunocytochemical staining for PCNA was performed on paraffin-embedded tissue sections and the number of endothelial cells staining for PCNA per 10 high-power fields (HPF) was determined. Rats fed CO + E and FO + E developed pathological changes, whereas none of the histologic features of ALD were seen in SF + E rats. The severity of injury was reduced in the quinone and cimetidine-treated groups. A higher rate of EC proliferation (6-30x) was seen in the SF + E group (no liver injury) than in the CO + E and FO + E groups (pathologic changes present). The difference was evident by 1 week, which is well before pathologic changes can be recognized (usually 4 weeks). An increase in EC proliferation was seen in the E3330 and cimetidine-treated groups. Our study indicates that the proliferative response of EC in ethanol-fed rats may be a factor in the progression to liver injury. Suppression of ethanol-induced EC proliferation in CO + E and FO + E groups occurred prior to development of liver injury; a lack of suppression of EC proliferation is associated with absence (SF + E and CO + E + cimetidine) or reduction in severity (CO + E + E3330) of liver injury.
Nanji
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AA
Department of Pathology, New England Deaconess Hospital, Boston, Massachusetts, USA.
Tahan
S R
SR
D000818:Animals; D016227:Benzoquinones / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002927:Cimetidine / Q000627:therapeutic use*; D003314:Corn Oil / Q000494:pharmacology; D004032:Diet; D004727:Endothelium / Q000166:cytology / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000633:toxicity; D005395:Fish Oils / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011422:Propionates / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D016227:Benzoquinones; D005395:Fish Oils; D018809:Proliferating Cell Nuclear Antigen; D011422:Propionates; C075569:E 3330; D000431:Ethanol; D003314:Corn Oil; D002927:Cimetidine