INHIBITION OF RESPIRATION AND GLUCONEOGENESIS BY PARACETAMOL IN RAT-KIDNEY PREPARATIONS

Paracetamol, at concentrations up to 10 mM, caused a reversible, concentration-dependent inhibition of respiration in isolated rat-kidney tubules metabolizing glucose, glutamine, lactate or glutamate. It also strongly inhibited the synthesis of glucose from glutamine or lactate and brought about a significant fall in the cell ATP level. Paracetamol lowered both coupled and uncoupled respiration in isolated kidney mitochondria oxidizing glutamate, but had no effect on respiration supported by succinate. Experiments with submitochondrial particles revealed that the drug did not influence the activity of NADH dehydrogenase but slowed the rate at which electrons were transferred from reduced NADH dehydrogenase to cytochrome b. The implications of these findings for paracetamol cytoxicity are discussed. © 1979.