Fructose 1,6-bisphosphate protects against D-galactosamine toxicity in isolated rat hepatocytes.
Incubation of hepatocytes with D-galactosamine (GalN) produced a dose-dependent alteration in cell viability and a fall in ATP and fructose 2,6-bisphosphate (Fru-2,6-P2) levels. The reduction in Fru-2,6-P2 can be explained by changes in the substrates or modulators of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase, because neither the adenosine 3',5'-cyclic monophosphate level nor the activity ratio of the enzyme was modified. Microcalorimetric measurements showed that GalN produced an exothermic peak followed by a progressive decrease in heat dissipation. Simultaneous administration of GalN and fructose 1,6-bisphosphate (Fru-1,6-P2) significantly increased cell viability, and concentrations of ATP and Fru-2,6-P2 and led to stable heat production. In the presence of Fru-1,6-P2 alone, hepatocytes kept ATP and Fru-2,6-P2 levels constant, whereas they increased the oxygen uptake-to-heat output ratio. Our results suggest that GalN initiates the hepatotoxic effect by means of an energy-dissipating interaction, produced before its metabolism and presumably at the membrane level, whereas Fru-1,6-P2 protects the cells against this injury in a way that prevents the initial interaction and increases the metabolic efficiency of the cell.
Unitat de Biofísica, Facultat d'Odontologia, Universitat de Barcelona, Spain.
T
T
Roig
J R
JR
De Oliveira
R
R
Bartrons
J
J
Bermúdez
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005635:Fructosediphosphates / Q000378:metabolism / Q000494:pharmacology*; D005688:Galactosamine / Q000506:poisoning*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D005635:Fructosediphosphates; D005688:Galactosamine; D000255:Adenosine Triphosphate; C029063:fructose-1,6-diphosphate