The pathology and biochemistry of paraquat.
After the administration of paraquat to rats the lung is the organ most severely damaged. The pathology in the lung can be divided into two distinct phases: (1) a destruction phase lasting a few days with damage to the type I and type II alveolar epithelial cells, oedema and haemorrhage (most of the rats which die after dosing with paraquat do so during this phase); (2) a reparative phase with regeneration of the epithelium and, in areas of severe damage, a characteristic proliferation of fibroblasts. In both phases of the lesion the death of the rats results from anoxia. Paraquat is selectively accumulated by the rat lung in comparison with other tissues and this accounts, at least in part, for the specific toxic effect in this organ. The accumulation into the lung was shown by in vitro studies to depend on energy and is inhibited by various endogenous and exogenous compounds. This uptake process is not that which has been described for 5-hydroxytryptamine and evidence is presented to suggest that the type I and type II alveolar epithelial cells are sites of accumulation. When paraquat is present in lung cells, it undergoes a cyclical reduction and oxidation with the production of superoxide anion. This radical may lead directly or indirectly to the formation of lipid peroxides and hence to cell death. However, paraquat stimulates the pentose-phosphate pathway and both reduces the level of NADPH and inhibits fatty acid synthesis in the lung. These effects occur when there is only minimal ultrastructural damage to the lung cells. It is suggested, therefore, that the primary mechanism of toxicity of paraquat is the extreme oxidation of NADPH which inhibits vital physiological processes and renders the cell more susceptible to attack from lipid hydroperoxides.
D000818:Animals; D001692:Biological Transport; D005227:Fatty Acids / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010269:Paraquat / Q000378:metabolism / Q000633:toxicity*; D012701:Serotonin / Q000378:metabolism; D014018:Tissue Distribution
D005227:Fatty Acids; D012701:Serotonin; D009249:NADP; D005979:Glutathione Peroxidase; D010269:Paraquat