The action of paraquat and diquat on the respiration of liver cell fractions.
1. Paraquat and diquat produce only a slight increase in the oxygen uptake of rat liver mitochondria, and it is likely that they do not penetrate the mitochondrial membrane. 2. In mitochondrial fragments inhibited by antimycin A or by Amytal, both substances stimulate oxygen uptake with NADH or beta-hydroxybutyrate as substrate but not with succinate. The NADH dehydrogenase of the respiratory chain appears to be involved, at a site only partially inhibited by Amytal. 3. An NADPH oxidase activity is stimulated in rat liver microsomes by diquat, and to a smaller extent by paraquat; diquat also causes an NADH oxidase activity to develop. The effect is not inhibited by carbon monoxide or p-chloromercuribenzoate, and it is probable that a flavoprotein is involved by a mechanism not requiring thiol groups. 4. One molecule of oxygen can oxidize two molecules of NADPH in the stimulated microsomal system, the hydrogen peroxide produced being broken down by a catalase activity in the microsomes. 5. Diquat can stimulate NADH oxidase and NADPH oxidase activity in the postmicrosomal soluble fraction; the enzyme involved may be DT-diaphorase. 6. The mechanism of these reactions and their significance in relation to the toxicity of the dipyridilium compounds are discussed.
D000654:Amobarbital; D000968:Antimycin A; D002248:Carbon Monoxide / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D002729:Chloromercuribenzoates / Q000494:pharmacology; D005415:Flavins; D006540:Herbicides / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D006885:Hydroxybutyrates / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008566:Membranes; D008861:Microsomes / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010088:Oxidoreductases; D010101:Oxygen Consumption / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013386:Succinates / Q000378:metabolism
D002729:Chloromercuribenzoates; D005415:Flavins; D006540:Herbicides; D006885:Hydroxybutyrates; D011725:Pyridines; D000644:Quaternary Ammonium Compounds; D013386:Succinates; D009243:NAD; D009249:NADP; D000968:Antimycin A; D002248:Carbon Monoxide; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D002374:Catalase; D000654:Amobarbital