A Useful Method for Differential Evaluation of Anti-Inflammatory Effects Due to Cyclooxygenase and 5-Lipoxygenase Inhibitions in Mice.
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概要
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This study was performed to establish a useful method for monitoring the effects of inhibitors of 5-lipoxygenase (5-LO) and/or cyclooxygenase (CO) and for differential evaluation of these inhibitors. After oral dosing, CO inhibitors such as indomethacin (20-40 mg/kg) and ketoprofen (40-80 mg/kg), zileuton (5-LO inhibitor, 20-80 mg/kg) and MK886 (5-LO-activating-protein inhibitor, 640 mg/kg) potently suppressed arachidonic acid (AA, 0.25 mg)-induced ear edema in mice. Methysergide (serotonin antagonist, 20 mg/kg) showed a slight anti-edematous effect, while mepyramine (160 mg/kg) and bromelain (320 mg/kg) had no effect. The anti-edematous effects of indomethacin and ketoprofen were reduced by concomitant topical application of prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>, 1 μg/ear), but not by concomitant intradermal application of leukotriene C<SUB>4</SUB> (LTC<SUB>4</SUB>, 0.1 μg/ear). On the contrary, the anti-edematous effects of zileuton and MK886 were reduced by LTC<SUB>4</SUB>, but not by PGE<SUB>2</SUB>. Dual (5-LO and CO) inhibitors such as phenidone (80-160 mg/kg) and BW755C (40-80 mg/kg), which inhibited the biosynthesis of LTB<SUB>4</SUB> 13-15 times more potently than that of PGE<SUB>2</SUB> in rat peritoneal exudate cells, also showed anti-edematous effects that were reduced by LTC<SUB>4</SUB>, but not by PGE<SUB>2</SUB>. These results suggest that the AA (0.25 mg)-induced ear edema in mice is mainly mediated by LTs and PGs and is suitable for evaluating inhibitors of 5-LO and/or CO, and that an application of LTC<SUB>4</SUB> or PGE<SUB>2</SUB> with AA is a useful method for differential evaluation of these inhibitors.
- 公益社団法人 日本薬理学会の論文
著者
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Ishii Katsumi
Department Of Pharmacology Exploratory Research Laboratories Dainippon Pharmaceutical Co. Ltd.
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Takeyama Kunihiko
Department Of Hematology Harasanshin General Hospital
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Takeyama Kunihiko
Department of Pharmacology, Exploratory Research Laboratories, Dainippon Pharmaceutical Co., Ltd.
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Ishii Katsumi
Department of Pharmacology, Exploratory Research Laboratories, Dainippon Pharmaceutical Co., Ltd.
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Motoyoshi Satoru
Department of Pharmacology, Exploratory Research Laboratories, Dainippon Pharmaceutical Co., Ltd.
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Kawata Joe
Department of Pharmacology, Exploratory Research Laboratories, Dainippon Pharmaceutical Co., Ltd.
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Nakagawa Hiroyo
Drug Regulatory Affairs, Dainippon Pharmaceutical Co., Ltd.
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- A Useful Method for Differential Evaluation of Anti-Inflammatory Effects Due to Cyclooxygenase and 5-Lipoxygenase Inhibitions in Mice.