The Effect of Paraquat on the Respiration of Lung Cell Fractions

SUMMARY The in vitro effects of paraquat on the aerobic metabolism of lung and liver homogenates, as well as on the oxygen consumption of isolated rat and rabbit lung mitochondria, were investigated. It was found that the endogenous oxygen uptake of a 40% lung homogenate was similar to that of a 10% liver homogenate, and that succinate (20 mM) was well oxidized by both homogenates. About 14% of the basal respiration rate was due to cyanide-insensitive oxidative systems in lung and liver homogenates. Paraquat (1 mM and higher concentrations) induced an acute and highly significant .increase in the cyanide-insensitive oxygen utilization. We were able to recover about 5% of the protein in the supernatant (1 000 g) of the original homogenate as mitochondrial protein. Only results obtained from mito­ chondrial preparations with a respiratory control ratio between 2,7 and 3,3 were used in the final analyses, and the normal state 3 respiration values of rabbit and rat lung mitochondria were 45,2 -l- 5,3 and 38,7 -l- 2,9 nmol oxygen per mg protein per minute respectively. Paraquat in concentrations up to 0,5 mM had no sig­ nificant effect, but higher concentrations up to 1 mM induced a highly significant inhibition of mitochondrial oxygen consumption. When slices were pre-incubated with 1 mM and with 0,01 mM paraquat in the incubation medium, the oxygen consumption of the mitochondria isolated after 2 hours and 4 hours respectively, was sig­ nificantly reduced. S. Afr. med. J' t 54, 1101 (1978). The puhnonary toxicity of paraquat is well docuDlented,'" but the DlechanisDl of its action has not yet been de­ finitely established. Previous reports on the effects of para­ quat on the in vitro oxygen consuDlption of lung slices'" indicated an initial sharp increase in the oxygen uptake which was followed by a gradual inhibition of the rate of oxygen utilization. The increase in aerobic metabolism seemed to be glucose-dependent, but the inhibitory action of paraquat appeared to be of the same magnitude, whether glucose was present or not.' It was speculated that the most probable mechanism of inhibition lay at a mitochondrial level, because the contribution of the