C. Bridges
Jul 1, 1957
Citations
0
Influential Citations
35
Citations
Quality indicators
Journal
The Biochemical journal
Abstract
1. A study has been made of the fate of salicylohydrazide and its N-acetyl derivative, and of salicylohydroxamic acid and its 5-bromo derivative, in the rabbit. The last two compounds have also been studied in man, rat and mouse. 2. Salicylohydrazide is metabolized mainly by conjugation with glucuronic acid (55% of dose), and partly by hydrolysis to salicylic acid, which is excreted largely as salicyluric acid. 3. N1-Acetyl-N2-salicyloylhydrazine is not deacetylated and is excreted mainly as its glucuronide (70% of the dose). These hydrazides do not form ethereal sulphates. Their glucuronides have been isolated. 4. Salicylohydroxamic acid is metabolized by direct conjugation with glucuronic and sulphuric acids in the rabbit, and there is practically no conversion into salicylamide. The glucuronide was isolated. In man, mouse and the rat, it forms considerable amounts ofsalicylamide, which is excreted conjugated. 5. 5-Bromosalicylohydroxamic acid is excreted by man, mouse, rabbit and rat mainly as conjugates of 5-bromosalicylamide, and to a lesser extent as the glucuronide of 5-bromosalicylohydroxamic acid. The glucuronides of the amide and the hydroxamic acid were isolated from rabbit urine. 6. The in vitro tuberculostatic activity of 5bromosalicylamide is about half that of 5-bromosalicylohydroxamic acid, its precursor in vivo. 7. The toxicity of aroyl hydrazides and hydroxamic acids in relation to their metabolism has been discussed. We wish to thank Professor R. Cruickshank for making available the facilities for bacteriological investigations. One of us (W.M.M.) is grateful to St Mary's Hospital Medical School and to the Leverhulme Trust for Research Fellowships.