Grant-in-Aid International Scientific Research
|Allocation Type||Single-year Grants|
|Research Institution||Azabu University|
AKAHORI Fumiaki Azabu Univ., School of Vet. Med., Professor, 獣医学部, 教授 (70063964)
MATSUDA Motoo Azabu Univ., AURIB., Associate Professor, 生物科学総合研究所, 助教授 (50139531)
FUJISE Hiroshi Azabu Univ., School of Vet. Med., Associate Professor, 獣医学部, 助教授 (40106232)
MASAOKA Toshio Azabu Univ., School of Vet. Med., Associate Professor, 獣医学部, 助教授 (30063978)
KOBAYASHI Kosaku Azabu Univ., School of Vet. Med., Professor, 獣医学部, 教授 (80063949)
KOBAYASHI Sadao Azabu Univ., Coll. of Environmental Health, Professor, 環境保健学部, 教授 (40105820)
OEHME Freder Kansas State Univ., Coll. Vet. Med. ・, Professor
OEHME Frederick W. Kansas State Univ., Coll. Vet. Med., Professor
FREDERICK Oe Kansas State Univ, Coll. Vet. Med. ・, Professor
|Project Period (FY)
1989 – 1991
Completed(Fiscal Year 1991)
|Budget Amount *help
¥5,030,000 (Direct Cost : ¥5,030,000)
Fiscal Year 1991 : ¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 1990 : ¥830,000 (Direct Cost : ¥830,000)
Fiscal Year 1989 : ¥900,000 (Direct Cost : ¥900,000)
|Keywords||Paraquat / pulmonary / fibrosis / macrophage / Toxicity / therapeutic / Taurine / Chlorpromazine / ビ-グル犬 / ディハイドロプロリン / 画像解析 / 結合組織性線維 / 種差 / チオネイン遺伝子|
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.