Paraquat-induced Pulmonary Fibrosis.

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The purpose of this investigation is to study the mechanisms of Paraquat (PQ) -induced pulmonary fibrosis with the objective of developing a therapeutic agent for the lung fibrosis.In the sedimentary cells of bronchoalveolar lavage-fluid from rhesus monkeys given PQ were mainly dependent upon the increase of neutrophils and type III and type IV pulmonary alveolar macrophages (PAM). These types of increases in PAM are suggestive that, by their activation, many kinds of biologically active substances, e. g. superoxide and lysosomal enzymes, which might have some relationship to the pathogenesis of PQ-induced pulmonary injury, are released.In the study is using the rats, the concentrations of lung coenzyme. Q_9 and coenzyme Q_<10> were decreased from 1 to 3 days after the 40mg/kg PQ injection compared to the control group. This result supports the concept that the mechanism of PQ toxicity is due to injury of an essential component of the electron transport chain in mitochondria of animals.In the study of development of therapeutic agents for the PQ poisoning, we were investigated many kinds of therapeutic agents, e. g. N-acetyl-L-Cysteine, L-Cystein, dl-tocopherol-L-ascolbic acid potassium, Coenzyme Q_<10>, Chlorpromazine, L-dehydroproline and taurine, which were an able to detoxication of PQ.No effects of these almost therapeutic agents on the bioparameters and/or lethal toxicity of PQ was observed. However, the effect of taurine (TA) on acute PQ intoxication was investigated in rats. This results suggest that a long continuous infusion of 5% TA increased urine output and inhibits of PQ accumulation in renal tissue despite arise in blood PQ concentration.