MITOCHONDRIAL ATPASE - A TARGET FOR PARACETAMOL-INDUCED HEPATOTOXICITY

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.