Histochemical and biochemical studies on the effect of the prostacyclin derivative iloprost on CCl4-induced lipid peroxidation in rat liver and its significance for hepatoprotection.
In the present study, it was investigated whether the prostacyclin derivative Iloprost would protect hepatocytes against CCl4-induced liver injury and which mechanism(s) of hepatocellular pathogenesis might be affected by it. Rats were treated with a single oral dose of CCl4 (2 ml per kg); Iloprost was infused continuously from 2 to 4 hr before intoxication until killing. The following results were obtained. The CCl4-induced release of AST, lactate dehydrogenase and alkaline phosphatase into the serum was reduced by 50 to 70% in rats treated with doses of 0.1 and 0.5 micrograms Iloprost per kg per min. Infusion of 0.02 and 0.004 micrograms Iloprost per kg per min did not affect the CCl4-induced enzyme release into the blood. CCl4 induced the occurrence of aldehydes (products of lipid peroxidation), which were detected by histochemical and biochemical means. At 12, 48 and 72 hr after CCl4, the aldehyde-positive liver section area was about 58, 69 and 16% in rats treated with CCl4 alone, but only about 18, 13 and less than 1% in rats treated additionally with Iloprost. The aldehyde-positive hepatocytes were located predominantly in the centrilobular zone of the liver. At 24 hr the extent of the aldehyde-positive section area was the same in rats with or without Iloprost treatment (about 90%). Biochemical determination, however, revealed that at this time point the malondialdehyde content after Iloprost in rats was about 70% lower than without Iloprost treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Bursch
W
W
Institut für Tumorbiologie-Krebsforschung, Vienna, Austria.
Taper
H S
HS
Somer
M P
MP
Meyer
S
S
Putz
B
B
Schulte-Hermann
R
R
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000037:antagonists & inhibitors; D011464:Epoprostenol / Q000494:pharmacology*; D016285:Iloprost; D007260:Infusion Pumps; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008938:Mitosis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D008315:Malondialdehyde; D002251:Carbon Tetrachloride; D011464:Epoprostenol; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase; D016285:Iloprost