Dv. Parmar et al., MITOCHONDRIAL ATPASE - A TARGET FOR PARACETAMOL-INDUCED HEPATOTOXICITY, European journal of pharmacology. Environmental toxicology and pharmacology section, 293(3), 1995, pp. 225-229
We examined the effect of paracetamol treatment (650 mg/kg) on the fun
ction of the ATPase from rat hepatic mitochondria. The drug treatment
caused an overall 35% decrease in ATPase activity, with a complete los
s of the high affinity component as determined by substrate kinetic st
udies. The K-m for the intermediate and low affinity components decrea
sed by about 30% without change in V-max, which may represent a compen
satory mechanism. The drug treatment also resulted in a dramatic decre
ase in the phase transition temperature by about 19 degrees C without
affecting the energies of activation of the enzyme. Mitochondrial tota
l phospholipid content increased significantly with a reciprocal decre
ase in the cholesterol content. The total phospholipid/cholesterol mol
ar ratio increased by 50% after paracetamol treatment. However, phosph
olipid composition (as % of total) of the mitochondria was unaltered.