Altered kinetic properties of liver mitochondrial membrane-bound enzyme activities following paracetamol hepatotoxicity in the rat.

ABSTRACT

The effects of treatment with subtoxic (375 mg/kg) and toxic (750 mg/kg) doses of paracetamol on NADH oxidase, succinoxidase and Mg2+-ATPase activities in rat liver submitochondrial particles were examined. In the NADH oxidase system, treatment with subtoxic doses of paracetamol resulted in a 37% increase in activation energy in the high temperature range (E1) while the phase transition temperature (Tt) for this system decreased by 9°C. Subtoxic doses caused a 43% decrease in E1. For the succinoxidase system, Tt decreased by 2·4 to 3·4°C after paracetamol administration. E2 increased by 42% only in the subtoxic-treatment group while E1 remained unaltered in both paracetamol-treated groups. For the Mg2+-ATPase system, subtoxic doses of paracetamol treatment did not change the values of E1, E2 and Tt whereas toxic dose treatment resulted in a 29% decrease in E2 with a concomitant increase in Tt by 2·4°C without any change in the value of E1 · The results thus suggest that treatment with toxic and subtoxic doses of paracetamol results in possible differential alterations in the membrane lipid milieu.