Cytoprotective effect of the prostacyclin derivative iloprost against liver cell death induced by the hepatotoxins carbon tetrachloride and bromobenzene.
It was investigated whether the prostacyclin derivative Iloprost (Schering, Berlin) protects rat hepatocytes against lethal damage induced by carbon tetrachloride (CCl4) and bromobenzene (BB). Iloprost was tested in whole animal experiments (intoxication with 2 ml CCl4/kg) and with primary hepatocyte cultures (intoxication with 1.6 mM BB). Cell damage was estimated by light microscopic examination of hepatocellular morphology and by the release of hepatocellular enzymes (glutamic-pyruvic transaminase, GPT; glutamic-oxalacetic transaminase, GOT; lactic dehydrogenase, LDH) into the blood or culture medium. In both experimental set-ups, Iloprost (0.1 micrograms/kg/min in whole animal experiments and 10(-9)-10(-12) M in primary hepatocyte cultures) largely preserved normal hepatocellular morphology after intoxication. Furthermore, the toxin-induced release of hepatocellular enzymes into the blood (GOT, GPT) or into the culture medium (LDH) was reduced by 50%-70% in the presence of Iloprost. It is concluded that the prostacyclin derivative Iloprost possesses cytoprotective activity on rat hepatocytes against lethal injury by CCl4 or BB.
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001969:Bromobenzenes / Q000037:antagonists & inhibitors*; D002252:Carbon Tetrachloride Poisoning / Q000188:drug therapy*; D056486:Chemical and Drug Induced Liver Injury; D011464:Epoprostenol / Q000494:pharmacology / Q000627:therapeutic use*; D016285:Iloprost; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008107:Liver Diseases / Q000473:pathology; D008297:Male; D009336:Necrosis; D051381:Rats
D001969:Bromobenzenes; C032036:bromobenzene; D011464:Epoprostenol; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D016285:Iloprost