EFFECT OF D-GLUCARIC ACID DERIVATIVES ON STABILITY OF RAT LIVER LYSOSOMES AND ERYTHROCYTES
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概要
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For studies on the lysosome-stabilizing effect of D-glucaric acid derivatives which have been found to have anti-inflammatory effects, the available and soluble enzyme activities of acid phosphatase of rat liver lysosomes were determined. Salicyclic acid and phenylbutazone which are well-known lysosome-stabilizers were employed as standards. Lysosomes were incubated with drugs under specific conditions which allowed the data on the stabilizing activity of the drugs to be reproducible. The inhibitory effects of D-glucaro-l, 4-lactone, salicylic acid and phenylbutazone on the increase in the available enzyme activity and the increase in the soluble enzyme activity appear to have a close correlation. The lysosome-stabilizing effect of D-glucaro-1, 4-lactone was the greatest among the D-glucaric acid derivatives and was greater than that of salicyclic acid and phenylbutazone over a wide range of concentrations. D-glucaro-1, 4-lactone as well as salicylic acid exhibited concentration-dependent lysosome-stabilizing effect whereas phenylbutazone had an optimum concentration for its lysosome-stabilizing effect. In addition, D-glucaro-l, 4-lactone, salicylic acid and phenylbutazone were also examined for their effects on heat-induced and saponin-induced hemolysis of rat erythrocytes. Both salicylic acid and phenylbutazone exhibited potent stabilizing and labilizing effects on heat-induced and saponin-induced hemolysis of erythrocytes, respectively. D-glucaro-1, 4-lactone, however, was incapable of affecting the hemolysis of erythrocytes. There appears to be a difference in the mechanism of the lysosome-stabilizing effects between D-glucaric acid derivatives and other anti-inflammatory drugs.
- 社団法人 日本薬理学会の論文
著者
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NAGASHIMA Renpei
Department of Pharmacology, Research Laboratories, Chugai Pharmaceutical Co., Ltd.
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Suzuki Shigeo
Department Of Applied Biological Chemistry The University Of Tokyo
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Nakano Hideki
Department Of Cardiovascular Surgery
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Matsushita Hiroshi
Department Of Applied Chemistry Faculty Of Engineering Okayama University
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FURUNO Koji
Department of Pharmacology, Research Laboratories, Chugai Pharmaceutical Co., Ltd.
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SUZUKI Shigeo
Department of Pharmacology, Research Laboratories, Chugai Pharmaceutical Co., Ltd.
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NAKANO Hideki
Department of Pharmacology, Research Laboratories, Chugai Pharmaceutical Co., Ltd.
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