H. Bostroem, K. Berntsen, M. Whitehouse
Mar 1, 1964
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Influential Citations
94
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Journal
Biochemical pharmacology
Abstract
Abstract The following anti-inflammatory drugs which inhibit the metabolism of cartilage and other connective tissues in vitro , also inhibit the biosynthesis of polysaccharide sulphates by rat rib cartilage in vivo : Salicylate, phenylbutazone, oxyphenbutazone, hydrocortisone, cinchophene, glycyrrhetic acid and flufenamic acid. 2,4-Dinitrophenol was also a potent drug in vivo , but 2,5-dinitrophenol was not. Drug action on cartilage metabolism could not be attributed to competition by the drug for available ‘active sulphate’ (PAPS). Salicylate, phenylbutazone, oxyphenbutazone, flufenamic acid and 2,4-dinitrophenol all depressed the excretion of sulphate esters in the urine. It is concluded that the latter drugs uncouple oxidative phosphorylation in the whole animal both in peripheral tissues such as cartilage and in those visceral tissues such as kidney and liver, which are concerned with the biosynthesis of sulphate esters. This property of the drugs in vivo may underlie their anti-inflammatory activity. Chloroquine and 8-hydroxyquinoline had no activity on cartilage metabolism in vivo in acute experiments. Evidence was obtained that nearly all the compounds listed in Table 1 were metabolised in the rat and excreted in the urine, in part at least—as ester sulphates. The urinary excretion of sulphated metabolites of phenylbutazone and hydrocortisone by rats was dependent on strain and sex.