Joseph Green

Adjuvant-induced arthritis and drug-metabolizing enzymes

Abstract Rats given a single intradermal injection into the foot pad of 0.50 mg Mycobacterium butyricum , suspended in 0.1 ml of liquid paraffin, developed arthritis after a latent period of about 8 days. However, a decline in the activity of hepatic aminopyrine demethylase and the level of cytochrome P-450 occurred before the development of arthritis. Rats given the adjuvant preparation by the intraperitoneal route showed also a decreased activity of aminopyrine demethylase. An inverse correlation was found between the level of α 2 -globulin and aminopyrine demethylase activity. Rats in which arthritis was induced by Mycoplasma arthritidus also showed a reduced activity of aminopyrine demethylase. The reduction of aminopyrine demethylase activity in adjuvant-treated rats was not caused by anorexia, neither could it be shown to be caused by a circulating hormonal factor. However, it was noted that the serum from many of the arthritic rats was greenish in colour and this might have been caused by the breakdown of certain haem compounds. The haem saturation of hepatic tryptophan oxidase was much less in adjuvant-induced arthritic rats than in controls. These results suggest a failure in haem biosynthesis and/or an accelerated breakdown of existing haem.

Biologically active substances

Certain novel esters of a specific group of non-ionic surfactants are useful as hypocholesterolaemic agents in animals and man. The compounds have a nucleus based on ethylene diamine and (C2H4O) groups accounting for 0 to 30% of the total molecular weight and (C3H6O) groups having a partial molecular weight of from 2250 to 3250. The esters may be formed from aliphatic, aromatic, amino-aliphatic or amino-aromatic acids.

Dietary fibre and sterol metabolism in the rat

I. Sterol metabolism was studied in rats fed on a semi-synthetic fibre-free diet and in rats fed on diets containing cellulose (200 or roo g/kg) or sugar-cane fibre (bagasse) at the same levels. 2. Rats fed on the diets containing cellulose or bagasse produced significantly greater quantities of faeces than did rats fed on the fibre-free diet. 3. Rats given bagasse excreted more bile acid and more neutral sterol in their faeces than did rats fed on cellulose or on the fibre-free diet. 4. After 28 d, hepatic synthesis of cholesterol (from acetate) and cholesterol 7a-hydroxylase activity were significantly higher in animals fed on bagasse than in animals fed on the other two diets. 5. No significant differences in serum cholesterol levels were seen in rats fed on any of the three diets. 6 . Food consumption was not substantially altered by the inclusion of bagasse or cellulose in the diets, although the efficiency of foodstuff utilization was generally lower. 7. Bagasse adsorbed substantial quantities of cholic acid in vitro, whereas cellulose did not. The lignin fraction prepared from bagasse contributed only slightly to the total bile acid-binding capacity of bagasse. 8. The results are discussed in the light of possible effects of dietary fibre on sterol metabolism in man.

Effect of 6-ethoxy 2,2,4-trimethyl-1,2-dihydro-quinoline (ethoxyquin) on carbon tetrachloride metabolism in the rat

Abstract Prior administration of ethoxyquin to rats partially prevented the hepatotoxic effects of CCl 4 . In rats, given an oral dose of 4 CCl 4 (2 ml/kg), ethoxyquin pretreatment enhanced the overall rate of elimination in the expired air of both 14 CCl 4 and 14 CO 2 . However, the rate of metabolism of CCl 4 by liver homogenates was not affected by the ethoxyquin pretreatment. The results support the view that ethoxyquin selectivity induces a CCl 4 -detoxification pathway.

Tetronic 701 — A novel hypocholesterolaemic agent

The Tetronic series of polymeric surface-active agents were screened for hypocholesterolaemic activity in rats fed on a semi-synthetic hypercholesterolaemic diet. Only Tetronics 701 and 702 were active and the former was further investigated. Tetronic 701 lowered serum and liver cholesterol in rats fed on a semi-synthetic diet, with or without cholesterol, but not in rats fed on stock laboratory diet. A dose-related growth depression was observed. The compound was hypocholesterolaemic in chicks and rabbits fed on cholesterol-containing diets. The uptake of a single dose of cholesterol into liver and serum was inhibited in rats given Tetronic 701. Tetronics 701 and 702 were effective in precipitating cholesterol from mixed micelles in vitro. Non-hypocholesterolaemic Tetronics were inactive in this respect. A series of tetraesters of tetronic 701 were prepared and tested in rats fed on a semi-synthetic hypercholesterolaemic diet. Several were hypocholesterolaemic and the tetrabenzoate was of especial interest in that it depressed growth less than did Tetronic 701 itself.