Triglyceride disposition in isolated hepatocytes after treatment with hydrazine.
Treatment of animals with hydrazine causes the accumulation of triglycerides in the liver but the mechanism remains unclear. Therefore, the effect of hydrazine on hepatic triglyceride synthesis and subsequent transport was studied in a hepatocyte model, in vitro in order to isolate liver cells from extrahepatic influences. Hepatocytes were isolated and either incubated in suspension with [14C]palmitate in the presence of hydrazine (2-12 mM) or pre-incubated with [14C]palmitate, washed free of the fatty acid and then incubated with hydrazine (2-12 mM). Hydrazine resulted in a significant reduction in the incorporation of [14C]palmitate into triglycerides and reduction in the transportation of triglycerides out of cells. When [14C]palmitate was in the incubation medium, ATP levels were reduced by lower concentrations of hydrazine than have previously been reported. None of the concentrations of hydrazine used affected cell membrane integrity (viability) as measured by LDH leakage. The 14CO2 produced by the beta-oxidation of [14C]palmitate was also measured in short term incubations (30 min) carried out in sealed vessels. There was a dose dependent increase in 14CO2 produced by very low concentrations of hydrazine (0.01-0.1 mM) after which the effect was maximal and concentrations above 8 mM hydrazine decreased 14CO2 production. The data suggest that the inhibition of transportation of triglycerides out of cells by hydrazine may have a more important role in the accumulation of triglycerides in the liver than has been previously recognised. However, the model was not able to mimic the accumulation of triglycerides in hepatocytes seen in vivo.
Waterfield
C J
CJ
Toxicology Department, School of Pharmacy, University of London, UK.
Asker
D S
DS
Timbrell
J A
JA
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D002250:Carbon Radioisotopes; D002469:Cell Separation; D006834:Hydrazines / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D010168:Palmitates / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000096:biosynthesis / Q000378:metabolism*
D002250:Carbon Radioisotopes; D006834:Hydrazines; D010168:Palmitates; D014280:Triglycerides; D002245:Carbon Dioxide; C029424:hydrazine