The effect of paraquat on microsomal lipid peroxidation in vitro and in vivo

Rat lung and liver microsomes did not undergo lipid peroxidation in the absence of iron when incubated with NADPH and concentrations of paraquat ranging from 10 −7 to 10 −2 m. Paraquat also did not stimulate rat liver and lung microsomal peroxidation induced by added iron and NADPH, and was inhibitory at concentrations above 10 μ m. Similarly, no stimulation of peroxidation was produced by paraquat in rabbit or human lung microsomes; however, under similar conditions, paraquat enhanced NADPH/iron-dependent peroxidation in mouse lung and liver microsomes, apparently by facilitating reduction of iron by the mouse microsomes. In lung microsomes obtained from rats sacrificed at 12, 18, and 24 hr following a lethal dose of paraquat (50 mg/kg, ip), there was no loss of vitamin E or increase in susceptibility to in vitro peroxidization which would be expected if lipid peroxidation had occurred in vivo, although extensive lung damage developed during this time period. In addition, no decrease in peroxidizable polyunsaturated fatty acids was observed in lung homogenate or microsomes obtained from the paraquat-treated rats, although there was a significant reduction in the palmitate content of these fractions at 24 hr post injection. These results indicate that paraquat does not cause pulmonary toxicity by initiating peroxidation of lung lipids, and the decrease of palmitate in paraquat-damaged lungs is consistent with inhibition of fatty acid synthesis as an early event in the pathogenesis of paraquat toxicity.