Spongiform neuropathy induced in dogs by prolonged, low-level administration of 6-aminonicotinamide (6-ANA).
The objective of this study was to demonstrate the effects of prolonged exposure to 6-ANA at low dose-levels in dogs. A male and a female Beagle dog received daily oral repetitive doses of 1 mg/kg or less for 20 weeks. Both dogs showed lacrimation, conjunctivitis, reduced motility and anemia since the second week of treatment. The female dog was more affected than the male and at the end of treatment period it had tremor, hanging lower jaw, stepping gait of the hind limbs, hunched posture, and general debilitation. Post-mortem examination of the female dog revealed prominent brain edema with pressure atrophy of the dorsal cranial bones. Microscopic examination of the nervous system revealed spongiform neuropathy in both animals mainly affecting the telencephalic cortex and hippocampal fascia dentata, the substantia gelatinosa in the spinal cord and the dorsal root and autonomic ganglia. The changes were produced by vacuolation of astrocytes in the central nervous system and perineuronal satellite cells in the ganglia. Examination of the other organs revealed thymic atrophy and high hematopoietic activity of the bone marrow in both dogs. The male had severe interstitial edema and vacuolar degeneration of the testicular seminiferous tubules and the female had marked chronic pyelonephritis. This chemically induced spongiform neuropathy in dogs obviously represents a subchronic form of the "energy deprivation syndrome" induced by impaired glucose utilization. Vacuolar degeneration of the testicular seminiferous epithelium may have the same pathogenesis.
Department of Toxicology, NOVARTIS AG, Basel, Switzerland.
G J
GJ
Krinke
W
W
Classen
D015120:6-Aminonicotinamide / Q000633:toxicity*; D000284:Administration, Oral; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004285:Dogs; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D005260:Female; D008297:Male; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013723:Teratogens / Q000633:toxicity*; D013737:Testis / Q000187:drug effects / Q000473:pathology
D013723:Teratogens; D015120:6-Aminonicotinamide