Degeneration of the Rat and Canine Adrenal Cortex Caused by a-(1,4- Dioxido-3-methylquinoxalin-2-yl)-/V-methylnitrone (DMNM)

given at a dose of 22.5 mg/kg bid to four dogs for 14 days caused diminished adrenal cortical reserves as determined by decreased plasma cortisol (three dogs) and lower aldosterone levels (four dogs) following the intravenous infusion of ACTH. A dose of 100 mg/kg/day of DMNM administered to rats for 31 or 35 days resulted in significant decreases in blood glucose. Histologically, the adrenal glands of both species treated with DMNM for a maximum period of 21 days (dogs) and 35 days (rats) had widespread granular and vacuolar degeneration of the cortex. This degeneration in treated rats began in the zona reticularis and inner regions of the zona fasciculata and eventually involved the entire cortex including the zona glornerulosa. As a result of treatment, significant ultrastructural alterations within cells of the rat and canine adrenal cortex consisted of degeneration of the mitochondria and an increase in the numbers and lipolysis of lipid droplets. The ultrastructure of the zona reticularis and fasciculata was most severely affected. © 1985 Society of Toxicology. The compound a-{l,4-dioxido-3-methylquin- mine the sequential changes in the pathogen-oxalin-2-yl)-.N-methylnitrone (DMNM) has esis of the adrenal cortical degeneration, the been shown to be effective in inhibiting the ultrastructural pathology, and to determin