Effect of the non-steroidal anti-inflammatory drugs on the acyl-CoA synthetase activity toward medium-chain, long-chain and polyunsaturated fatty acids in mitochondria of mouse liver and brain.
Effect of eleven non-steroidal anti-inflammatory drugs on the acyl-CoA synthetase activities toward octanoic, palmitic, arachidonic and docosahexaenoic acids was evaluated in mouse liver and brain mitochondria. The drugs tested were aspirin, salicylic acid, diflunisal, mefenamic acid, indomethacin, etodolac, ibuprofen, ketoprofen, naproxen, loxoprofen, flurbiprofen. In mouse liver mitochondria, diflunisal and mefenamic acid exhibited the inhibitory activities not only for octanoic acid (IC(50) = 78.7 and 64.7 µM) and but also for palmitic acid (IC(50) = 236.5 and 284.4 µM), respectively. Aspirin was an inhibitor for the activation of octanoic acid only (IC(50) = 411.0 µM). In the brain, mefenamic acid and diflunisal inhibited strongly palmitoyl-CoA formation (IC(50) = 57.3 and 114.0 µM), respectively. The activation of docosahexaenoic acid in brain was sensitive to inhibition by diflunisal and mefenamic acid compared with liver.
Biochemical Toxicology Laboratory, Faculty of Pharmaceutical Sciences, Kobegakuin University, Kobe, Japan. kasuya@pharm.kobegakuin.ac.jp
Fumiyo
F
Kasuya
Misumi
M
Kazuhiro
Hasegawa
H
Tatsuya
Kazuo
K
Nakamoto
Shogo
S
Tokuyama
Teiichi
T
Masuyama
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology; D003066:Coenzyme A Ligases / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005231:Fatty Acids, Unsaturated; D004281:Docosahexaenoic Acids; D003066:Coenzyme A Ligases