Chem.-Biol. Interactions, 19 (1977) 143--160 ©ElsevierfNorth-Holland Scientific Publishers Ltd.
143
IN VIVO OXIDATION OF REDUCED NICOTINAMIDE-ADENINE DINUCLEOTIDE PHOSPHATE BY PARAQUAT AND DIQUAT IN RAT LUNG
HANSPETER WITSCHI*, SAM KACEW**, KEI-ICHI HIRAI*** and MICHEL G. CST~ D~partement de Pharmacologie, Facultd de M~deeine, Universit~ de Montreal, Montrdal (Canada) (Received April 28th, 1977) (Revision received August 3rd, 1977) (Accepted August 31st, 1977)
SUMMARY
Intravenous injection of rats with 156 pmol/kg of paraquat or 140 pmol/ kg of diquat produced, within 60 min, a sharp drop in the ratios of NADPH to NADP in lung. The effect persisted for a time period of at least 24 h. Exposure to 100% oxygen enhanced the toxicity of both compounds without substantially amplifying changes in the NADPH/NADP ratio. Lungs retained the capability to synthesize adenine nucleotides de novo. Electron microscopic studies showed that both paraquat and diquat damage type I alveolar cells, but only paraquat produces type II cen lesions. Although bipyridylium herbicides produce acute oxidation of NADPH in vivo, there seems not to exist a straightforward relationship between this event and cell damage.
INTRODUCTION
Paraquat (1,1'
143
IN VIVO OXIDATION OF REDUCED NICOTINAMIDE-ADENINE DINUCLEOTIDE PHOSPHATE BY PARAQUAT AND DIQUAT IN RAT LUNG
HANSPETER WITSCHI*, SAM KACEW**, KEI-ICHI HIRAI*** and MICHEL G. CST~ D~partement de Pharmacologie, Facultd de M~deeine, Universit~ de Montreal, Montrdal (Canada) (Received April 28th, 1977) (Revision received August 3rd, 1977) (Accepted August 31st, 1977)
SUMMARY
Intravenous injection of rats with 156 pmol/kg of paraquat or 140 pmol/ kg of diquat produced, within 60 min, a sharp drop in the ratios of NADPH to NADP in lung. The effect persisted for a time period of at least 24 h. Exposure to 100% oxygen enhanced the toxicity of both compounds without substantially amplifying changes in the NADPH/NADP ratio. Lungs retained the capability to synthesize adenine nucleotides de novo. Electron microscopic studies showed that both paraquat and diquat damage type I alveolar cells, but only paraquat produces type II cen lesions. Although bipyridylium herbicides produce acute oxidation of NADPH in vivo, there seems not to exist a straightforward relationship between this event and cell damage.
INTRODUCTION
Paraquat (1,1'
