E. Quilley, M. Smith
Sep 1, 1952
Citations
0
Influential Citations
14
Citations
Journal
Journal of Pharmacy and Pharmacology
Abstract
SALICYLATES have been found to cause a reduction in the glycosuria and hyperglycaemia of the alloxan-diabetic rat? Conjugation of the salicylates with glucuronic acid may have contributed to depletion of available glucose in these animals and was considered as a possible mechanism to explain the observed effects. Although glucuronic acid conjugates form a high proportion of salicylate metabolites in man2 and the dog3 the evidence for their occurrence in the rat is conflicting. Lutwak-Mann4 reported that the ability of the rat’s liver to form conjugated glucuronides from salicylate was negligible and could not detect such glucuronides in the urine of rats receiving salicylates. Schayer5 studied the metabolism of C14 carboxyl salicylic acid in the rat by paper chromatography and in addition to identifying salicylic, salicyluric and gentisic acids obtained two unidentified substances, of which one of low R, value could have been a glucuronide. In the present work the metabolism of salicylate in the rat has been investigated by a paper chromatographic method which gave a complete separation of the known metabolites which were quantitatively estimated. Previous observations in this species have only been qualitative in nature. The presence of glucose in the urine of rats receiving salicylates was reported by Lutwak-Mann4 and this observation is of great interest because of the reduction of glycosuria caused by salicylates in rats made diabetic either by partial pancreatectomy6 or alloxan? The urines of the rats which had been given salicylates were therefore examined for glucose by a paper chromatographic technique capable of detecting 1 pg. of the sugar. METHODS A descending method using one-dimension strips of Whatman No. 4 filter paper and a mixture of n-butanol 40, glacial acetic acid 4 and water 56 (all per cent. v/v) in an atmosphere of ammonia (0.2 per cent. w/v aqueous ammonia) was used. The solvents were based on those employed by Bray, Thorpe and White’ and Consden and Stanier.8 Each chromatogram was run for 16 hours and the salicylate compounds visualised by means of their fluorescence in ultra-violet light8 ; a Hanovia Chromalite lamp was used as the light source. For the qualitative identification of the metabolites in the urine of rats receiving salicylate, 5 pml. of each urine specimen was chromatographed and run in conjunction with a solution containing salicylic, salicyluric and gentisic acids as marker substances. Blood