Protective effect of malotilate against galactosamine intoxication in the rat.
The influence of malotilate was tested in a model of galactosamine (GalN) intoxication in the rat; two different experiments were carried out: (1) an acute intoxication (GalN at a single dose of 500 mg/kg s.c.): after pretreatment with malotilate (100 and 200 mg/kg p.o.) a marked reduction of hepatocellular injury, as shown by decrease of ASAT, ALAT and GlDH, was observed; (2) a subacute intoxication, GalN at 3 x 300 mg/kg s.c. for 3 consecutive days, which induced a more moderate hepatic necrosis: malotilate, 200 mg/kg/day p.o. for 4 days beginning the day before the first GalN injection, decreased significantly the disturbances of the biochemical measured parameters (plasma total proteins, prothrombin time, fibrinogen level, BSP clearance and hepatic total lipids) and accelerates the return to normal. Pathology studies revealed that pretreatment with malotilate increased markedly the number of mitoses observed in the hepatic cells after intoxication. In addition, the time of appearance of these mitoses was earlier in malotilate treated animals. From these studies, it can be concluded that malotilate protects against hepatocellular injury induced by GalN in the rat and that it stimulates the regenerative capacity of the liver after intoxication.
Research Department, Zyma SA, Nyon, Switzerland.
J M
JM
Dumont
M F
MF
Maignan
D
D
Perrissoud
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D005688:Galactosamine / Q000037:antagonists & inhibitors* / Q000506:poisoning; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008314:Malonates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D008314:Malonates; D005688:Galactosamine; C024808:diisopropyl 1,3-dithiol-2-ylidenemalonate