The relevance of pentose phosphate pathway stimulation in rat lung to the mechanism of paraquat toxicity

Abstract

Paraquat and diquat have been shown to stimulate the production of 14CO 2 from [1- 14C]-glucose by slices of rat lung, but not the production of 14CO 2 from [6- 14C]glucose. This indicates stimulation of the pentose phosphate pathway. Paraquat was effective at concentrations as low as 7.5 × 10 −7 M whilst a concentration of diquat of 10 −5 M was required for comparable stimulation. Maximal stimulation occurred with approximately 10 −5 M paraquat and approximately 10 −4 M diquat. The stimulation of pentose phosphate pathway in lung slices by paraquat has been shown to be related to paraquat accumulation. Lung slices from rats dosed intravenously with 65 μmoles of either paraquat or diquat/kg body wt had increased pentose phosphate pathway activity compared with slices from saline injected controls. At all times studied from 0.5 to 18 hr after injection, pentose phosphate pathway activity in slices from diquat poisoned rats was equal to or greater than that observed in slices from paraquat poisoned rats. Since only rats dosed intravenously with paraquat subsequently develop lung damage, it is concluded that there is no simple relationship between stimulation of the pentose phosphate pathway in lung and the production of lung damage.