Study on the toxicological mechanism of paraquat-induced pulmonary fibrosis and its tentative therapeutics
| Project/Area Number |
15590571
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Legal medicine
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
SHIONO Hiroshi (2004-2005) Asahikawa Medical College, Medical, Vice-President, 医学部, 副学長 (20112451)
清水 惠子 (2003) 旭川医科大学, 医学部, 助教授 (90312462)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUBARA Kazuo Asahikawa Medical College, Medical, Professor, 医学部, 教授 (20127533)
ASARI Masaru Asahikawa Medical College, Medical, Assistant, 医学部, 助手 (40360979)
AZUMI Jun-ichi Asahikawa Medical College, Medical, Associate Professor, 医学部, 助教授 (00045551)
SHIMIZU Keiko Asahikawa Medical College, Medical, Professor, 医学部, 教授 (90312462)
塩野 寛 旭川医科大学, 医学部, 教授 (20112451)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | paraquat / lung damage / oxidative stress / ACE inhibitor / NO / apoptosis / 腎障害 / ドパミン系 / 抗酸化作用 |
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| Research Abstract |
The Paraquat (1,1'-dimethyl-4,4'-bipyridinium, PQ) is a widely used herbicide and is an environmental factor that could be involved in the etiology of Parkinson's disease or at least, exposure to low levels of paraquat for a long time would make dopaminergic neuron vulnerable to oxidative stress and cell death. We have previously shown that paraquat penetrates through the blood-brain barrier and then generates cell death. On the other hand, it is well known that acute poisoning of paraquat induces lung damage, thus the paraquat is a pnemotoxicant possibly as an oxidative-stress inducing substance. However, there is not any effective treatment for paraquat poisoning.
In this study, we investigated peripheral acute toxicity, especially to the lung, induced by paraquat (50 mg/kg). The survival rate from paraquat poisoning was significantly higher in mice treated with anti-oxidative agents and/or angiotensin converting enzyme (ACE) inhibitor than control mice which were administered only paraquat. Dopamine transporter inhibitor and dopamine D2/3 agonists, which could be effective to prevent the neuronal damage caused by exposure to low doses of paraquat, did not improve the survival rate but promoted the pulmonary dysfunction caused by 50 mg/kg of paraquat. Since it is known that ACE inhibitor has an anti-oxidative effect, inhibition of oxidative stress might be a key role to reduce the toxicity induced by paraquat in lung. To investigate the oxidative-stress mechanism induced by paraquat in lung tissue, we determined the change of the level of cleaved caspase 3 relevant to apoptotic cell death using the western blot technique.
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] Tandospirone, a 5-HT1A agonist, ameliorates movement disorder via non-dopaminergic systems in rats with unilateral 6-hydroxydopamine-generated lesions.2006
Author(s)
K.Matsubara, K.Shimizu, M.Suno, K.Ogawa, T.Awaya, T.Yamada, T.Noda, M.Satomi, K.Ohtaki, K.Chiba, Y.Tasaki, H.Shiono
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Journal Title
Brain Research, (in press)
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Tandospirone, a 5-HT1A agonist, ameliorates movement disorder via non-dopaminergic systems in rats with unilateral 6-hydroxydopamine-generated lesions.2006
Author(s)
K.Matsubara, K Shimizu, M Suno, K.Ogawa, T.Awaya, T.Yamada, T.Noda, M.Satomi, K.Ohtaki, K.Chiba, Y.Tasaki, H.Shiono
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Journal Title
Brain Research (in press)
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Cefoselis, a beta-lactam antibiotic, easily penetrates the blood-brain barrier and causes seizure independently by glutamate release.2004
Author(s)
K.Ohtaki, K.Matsubara, S.Fujimaru, K.Shimizu, T.Awaya, M.Suno, K.Chiba, N.Hayase, H.Shiono
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Journal Title
Journal of Neural Transmission 12
Pages: 1523-1535
Description
「研究成果報告書概要(和文)」より
Related Report
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