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.