Paraquat toxicity.
Paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride) is marketed as a contact herbicide. Although it has proved safe in use there have been a number of cases of poisoning after the intentional swallowing of the commercial product. The most characteristic feature of poisoning is lung damage, which causes severe anoxia and may lead to death. The specific toxicity to the lung can be explained in part by the accumulation of paraquat into the alveolar type I and type II epithelial cells by a process that has been shown to accumulate endogenous diamines and polyamines. When accumulated, paraquat undergoes an NADPH-dependent, one-electron reduction to form its free radical, which then reacts avidly with molecular oxygen to reform the cation and produce superoxide anion, which in turn will dismutate to form H2O2. This may lead to the formation of more reactive (and hence toxic) radicals which have the potential to cause lipid peroxidation and lead to cell death. Biochemical changes provoked by paraquat in the lung suggest that it causes a rapid, pronounced and prolonged oxidation of NADPH that initiates compensatory biochemical processes in the lung. NADPH may be further depleted as it is consumed in an attempt to detoxify H2O2 or lipid hydroperoxides. Thus it is possible that with toxic levels of paraquat in the cell, compensatory biochemical processes are insufficient to maintain levels of NADPH consistent either with cell survival or with the ability to detoxify H2O2 or prevent lipid peroxidation.
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D000818:Animals; D005227:Fatty Acids / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000139:chemically induced*; D009249:NADP / Q000378:metabolism; D010269:Paraquat / Q000378:metabolism / Q000633:toxicity*; D010427:Pentose Phosphate Pathway; D013481:Superoxides / Q000378:metabolism
D005227:Fatty Acids; D005609:Free Radicals; D008054:Lipid Peroxides; D013481:Superoxides; D009249:NADP; D010269:Paraquat