Adrenocortical degeneration in dogs, monkeys, and rats treated with alpha-(1,4-dioxido-3-methylquinoxalin-2-YL)-N-methylnitrone.
The antibacterial compound alpha-(1,4-dioxido-3-methylquinoxalin-2-yl)-N-methylnitrone (DMNM), which was administered for a maximum period of 90 days, was given orally at 0, 7.5, 15.0 or 22.5 mg/kg/day for dogs; 0, 15, 50 or 100 mg/kg/day for rats; and 35 mg/kg/day for monkeys. Reduced food consumption and weight gain, depression, debility, and deaths occurred starting at doses (mg/kg/day) of 15 in dogs, 35 in monkeys and 50 in rats. Frequent emesis and occasional black, tarry feces were also observed in most treated dogs. Necropsy examinations revealed small, pale adrenal glands in rats given a dose of 50 mg/kg/day and gastrointestinal hemorrhage in dogs administered 15.0 or 22.5 mg/kg/day of DMNM. Microscopically, vacuolar degeneration of the canine, monkey and rat adrenal cortex was seen at all dosages and appeared to progress from the zona reticularis to the zona glomerulosa. In rats treated with 50 mg/kg/day of the drug chronic lesions of adrenal cortical fibrosis, atrophy, and nodular hyperplasia were also detected. The only other significant microscopic lesions consisted of mild testicular atrophy and occasional gastric erosions in dogs treated with 7.5 mg/kg/day of DMNM.
D000311:Adrenal Glands / Q000166:cytology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008253:Macaca mulatta / Q000033:anatomy & histology; D008297:Male; D051381:Rats; D013045:Species Specificity; D013270:Stomach / Q000166:cytology; D013737:Testis / Q000166:cytology; D013997:Time Factors
D000900:Anti-Bacterial Agents