Effect of neomycin on the hydrolysis and toxicity of vicine and convicine in rats.
This study in the rat established the effects that a broad-spectrum and poorly absorbed antibiotic, neomycin sulfate, had on the in vitro and in vivo hydrolysis of vicine and convicine by the intestinal microflora, and on vicine- and convicine-induced depletion of blood glutathione and the resulting toxicity. The in vitro studies demonstrated that digesta from the caecum and large intestine were highly effective in hydrolysing vicine and convicine, whereas digesta from the same sections of the gastro-intestinal tract of neomycin-treated rats were much less effective (P < 0.0001). The in vivo studies showed that the total amount of vicine and convicine excreted in the urine and faeces was much greater in neomycin-treated rats compared with controls (P < 0.05), indicating the ability of neomycin to increase the amount of glycosides, particularly that of vicine, excreted in the faeces. The ability of glycosides to decrease the concentration of glutathione in blood (P < 0.05) and to increase rat mortality was greatly reduced in rats that were treated with neomycin, particularly in those treated ip with the toxin. Thus, the results demonstrated that neomycin reduced the rate at which vicine and convicine were hydrolysed in the lower section of the gastro-intestinal tract, and that neomycin treatment was associated with a reduced toxicity of the glycosides.
Arbid
M S
MS
Department of Animal Science, University of Manitoba, Winnipeg, Canada.
Madhyastha
M S
MS
Marquardt
R R
RR
Frohlich
A A
AA
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D002432:Cecum / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D005243:Feces / Q000737:chemistry; D005766:Gastrointestinal Contents / Q000737:chemistry / Q000382:microbiology; D005960:Glucosides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D005978:Glutathione / Q000097:blood; D006868:Hydrolysis / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007420:Intestine, Large / Q000378:metabolism; D008297:Male; D009355:Neomycin / Q000008:administration & dosage / Q000494:pharmacology*; D011744:Pyrimidinones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014118:Toxins, Biological / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D014529:Uridine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity
D005960:Glucosides; D011744:Pyrimidinones; D014118:Toxins, Biological; C007116:convicine; C009661:vicine; D005978:Glutathione; D009355:Neomycin; D014529:Uridine