Use of prostaglandin I2 analog in treatment of massive hepatic necrosis associated with endothelial cell injury and diffuse sinusoidal fibrin deposition.
Endothelial cell damage causes massive hepatic necrosis as a result of fibrin deposition in the hepatic sinusoids. When a stable analog of prostaglandin I2, beraprost sodium, was administered to rats given either dimethylnitrosamine, carbon tetrachloride, or endotoxin following Corynebacterium parvum administration, the hepatic necrosis produced in each was attenuated, but to a greater extent in the dimethylnitrosamine and endotoxin/Corynebacterium parvum models, where fibrin deposition in the hepatic sinusoids occurs, as compared to the carbon tetrachloride model, where such fibrin deposition does not occur. Beraprost sodium reduced the expected increase of portal venous pressure in the endotoxin/Corynebacterium parvum model without affecting plasma thrombin-antithrombin III complex levels. Beraprost sodium also significantly reduced cell killing of both isolated rat hepatocytes and hepatic sinusoidal endothelial cells exposed to tert-butyl hydroperoxide when compared to controls. Beraprost sodium could prove to be a therapeutic candidate for the treatment of hepatic necrosis, particularly in cases associated with fibrin deposition in the hepatic sinusoids because of its fibrin clot-clearing action.
Fujiwara
K
K
Third Department of Internal Medicine, Saitama Medical School, Japan.
Mochida
S
S
Ohno
A
A
Arai
M
M
Matsui
A
A
Masaki
N
N
Hirata
K
K
Tomiya
T
T
Yamaoka
M
M
Nagoshi
S
S
D000818:Animals; D000990:Antithrombin III / Q000032:analysis; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D002251:Carbon Tetrachloride; D002478:Cells, Cultured; D004128:Dimethylnitrosamine; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D004731:Endotoxins; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005337:Fibrin / Q000378:metabolism*; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009336:Necrosis; D010447:Peptide Hydrolases / Q000032:analysis; D017082:Portal Pressure; D011425:Propionibacterium acnes; D011517:Prothrombin Time; D051381:Rats; D011916:Rats, Inbred F344
D004731:Endotoxins; C046193:antithrombin III-protease complex; C048081:beraprost; D000990:Antithrombin III; D005337:Fibrin; D002251:Carbon Tetrachloride; D011464:Epoprostenol; D010447:Peptide Hydrolases; D004128:Dimethylnitrosamine