[Inhibitory effects of prostaglandin E1.alpha-cyclodextrin (PGE1.CD) on dimethylnitrosamine-induced acute liver damage in rats].
The effects of PGE1.CD on dimethylnitrosamine (DMN)-induced acute liver damage with intravascular coagulation in rats were biochemically and histopathologically investigated. PGE1.CD was administered i.v. from 30 min before to 24 hr after DMN-intoxication (pretreatment) and from 30 min after or from 4 hr after to 24 hr after DMN-intoxication (post-treatment). Pretreatment with PGE1.CD (0.2-2 micrograms/kg/min) dose-dependently suppressed the decrease of platelet counts and the elevation of blood biochemical parameters (PT, HPT, GOT, GPT, LDH, LAP, T-Bil) caused by DMN-intoxication. PGE1.CD (0.5 microgram/kg/min and over) significantly suppressed the DMN-induced histopathological changes (occurrence of hemorrhage and necrosis). Post-treatment with PGE1.CD (2 micrograms/kg/min) also suppressed the liver damage. Furthermore, pretreatment with PGE1.CD (2 micrograms/kg/min) not only suppressed the disruption of hepatocytes, but also prevented the damages of sinusoidal endothelial cells and lysosomal membrane, and it reduced the increase of lipid peroxidation. PGE1.CD (1 microgram/kg/min and over) significantly suppressed the decrease of hepatic tissue blood flow caused by DMN-intoxication. These results demonstrate that PGE1.CD has therapeutically efficacy against DMN-induced acute liver damage in rats; Therefore, it will be clinically useful for the treatment of severe hepatitis such as fulminant hepatitis with intravascular coagulation in the sinusoid.
Suzuki
A
A
Minase Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
Hagino
M
M
Yasuda
N
N
Sagawa
K
K
Terawaki
T
T
Ogawa
M
M
Kondo
K
K
Hamanaka
N
N
Tanaka
M
M
Aze
Y
Y
D000208:Acute Disease; D000527:Alprostadil / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D003505:Cyclodextrins; D004128:Dimethylnitrosamine; D007262:Infusions, Intravenous; D008107:Liver Diseases / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D047391:alpha-Cyclodextrins
D003505:Cyclodextrins; D047391:alpha-Cyclodextrins; D000527:Alprostadil; D004128:Dimethylnitrosamine; C032613:alpha-cyclodextrin