Abstract:
: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.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Waterfield CJ,Asker DS,Timbrell JAdoi
10.1016/s0009-2797(97)00090-2subject
Has Abstractpub_date
1997-11-28 00:00:00pages
157-72issue
3eissn
0009-2797issn
1872-7786pii
S0009279797000902journal_volume
107pub_type
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