Effect of prostacyclin (PGI2) and a prostaglandin analogue BW 245C on galactosamine-induced hepatic necrosis.
The reported cytoprotective effects of prostaglandins against noxious stimuli in the liver was the basis for the present investigations of the effects of prostacyclin (PGI2) and a prostaglandin analogue (BW 245C) in an animal model of severe liver failure. Rats were given galactosamine at two dose levels and the prostaglandins were given in repeated doses from 0 to 6 h during the development of the liver damage or in another group from 24 to 30 h at the time of maximal liver injury. For PGI2 significant cytoprotection was found as assessed by a reduction in blood Normotest at 24, 48 and 72 h (P less than 0.05) and the plasma level of aspartate aminotransferase at 24 and 48 h (P less than 0.02) and the lysosomal markers N-acetyl-beta-glucosaminidase at 24, 48 and 72 h (P less than 0.001) and cathepsin D at 48 h (P less than 0.005) as compared to appropriate controls. Early administration of PGI2 reduced the mortality rate from 63% in the control group to 0% (P less than 0.01) in the treated group, but no significant effects were found when either compound was given later in the 24-h to 30-h period.
D000118:Acetylglucosaminidase / Q000032:analysis; D000818:Animals; D001219:Aspartate Aminotransferases / Q000032:analysis; D002402:Cathepsin D / Q000032:analysis; D011464:Epoprostenol / Q000494:pharmacology*; D005688:Galactosamine / Q000633:toxicity*; D006827:Hydantoins / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009336:Necrosis; D009712:Nucleotides, Cyclic / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
D006827:Hydantoins; D009712:Nucleotides, Cyclic; D005688:Galactosamine; C030669:BW 245C; D011464:Epoprostenol; D001219:Aspartate Aminotransferases; D000118:Acetylglucosaminidase; D002402:Cathepsin D