1987 Fiscal Year Final Research Report Summary
Chloroquine myopathy,its mechanism and treatment with cysteine proteinase inhibitor,EST
| Project/Area Number |
61570396
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | National Institute of Neuroscience,NCNP |
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Principal Investigator |
SUGITA Hideo National Institute of Neuroscience,Head, 神経研究所・疾病研究第一部, 室長 (80009951)
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| Co-Investigator(Kenkyū-buntansha) |
HIGUCHI Itsuro National Institute of Neuroscience,Research Associate, 神経センター・神経研究所・疾病研究第一部, 研究員 (80183573)
ARAHATA Kiichi National Institute of Neuroscience,Section Chief, 神経センター・神経研究所・疾病研究第一部, 室長 (30053325)
ISHIURA Shoichi National Institute of Neuroscience,Section Chief, 神経センター・神経研究所・疾病研究第一部, 室長 (10158743)
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| Project Period (FY) |
1986 – 1987
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| Keywords | Chloroquine myopathy / lysosome / cathepsins B and L |
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| Research Abstract |
Recently much attention has been paid to distal myopathy with remmed vacule formation (DMRV).The presence of high acid phosphatase in rimmed vacuole strongly suggests the role of lysosome in muscle fiber degeneration.
It was reported that long-term administration of high dosis of chloroquine caused vacuolar myopathy in rats.Histochemical investigation revealed an accumulation of acid phosphatase,and abundance of myeloid bodies which are essentially the same as DMRV. So,we have produced the chloroquine nyopathy in rats as a model of DMRV and coadministered a potent cysteine protease inhibitor,EST whether this druh could prevent and treat the chloroquine myopathy.
The administration of 50mg/kg/day of chloroquine to rats for 8 weeks produced the chloroquine myopathy characterized by autophagic bacuole formation and increase in lysosomal enzymes,especially cathepsins B,and L.Coadministration of 10mg/kg/day of EST by oral route and chloroquine prevented the induction of the chloroquine myopathy.Rats already suffered from the chloroquine myopathy were treated with 10mg/kg/day of EST together with chloroquine injections for 5 weeks.They also recovered remarkably from the myopathy,histochemically and biochemically.Thus, EST may be beneficial for not only DMRV but also related myopathies associated with autophagic vacuoles.
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[Publications] K.II,MD,K.Hizawa,MD,I.Nonaka,H.Sugita,MD,E.Dominami,MD,and N.Katunuma,MD: "Abnormal Increases of Lysosomal Cysteinine Proteinases in Rimmed Vacuoles in the Skeletal Muscle" Am J Pathol. 122(2). 193-198 (1986)
Description
「研究成果報告書概要(欧文)」より
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