Effects of pneumotoxic trialkylphosphorothioates on the pentose phosphate pathway in rat lung slices

The extent of glucose oxidation via the pentose phosphate pathway (PPP), a possible indicator of oxidative stress, was assessed in rat lung slices by measuring the production of 14CO2 on incubation with either [6-14C]glucose or [1-14C]glucose. Incubation in the presence of the pneumotoxins O,S,S-trimethyl phosphorodithioate (OSSMe, 10(-5) -10(-3) M), O,O,S-triethyl phosphorothioate (10(-4) -10(-2) M) or S,S,S-trimethyl phosphorotrithioate (10(-4) -10(-2) M) resulted in a significant, but small stimulation of PPP (max. 276%), compared to that found in the presence of the model oxidant, paraquat (1089%, 10(-5) M). Following in vivo treatment with an LD50 dose of OSSMe, PPP was unchanged (after 6 h) or decreased (after 24 h) compared to saline-treated rats. PPP was also decreased in slices which had been preincubated with OSSMe (10(-3) M) and then transferred to fresh medium. Following treatment with phorone (250 mg/kg i.p.) pulmonary levels of non-protein sulfhydryls were first reduced (20% of control at 3 h) and then increased (288% of control at 24 h), but at neither time was lung slice PPP activity affected, thus suggesting that in the rat lung PPP activity does not directly depend on pulmonary glutathione content.