Clioquinol and 2,5-hexanedione induce different types of distal axonopathy in the dog.
Krinke-G; Schaumburg-HH; Spencer-PS; Thomann-P; Hess-R
Acta Neuropathol 1979 Jan; 47(3):213-221
Neuropathological changes induced by 5-chloro-7-iodo-8- hydroxyquinoline (130267) (clioquinol) and 2,5-hexanedione (110134) (hexanedione) in dogs were compared. Beagle-dogs were administered 400mg/kg clioquinol daily orally for up to 7 months or 110mg/kg hexanedione daily for up to 5 months. They were observed for clinical signs of toxicity. Selected animals were killed at monthly intervals and samples of central and peripheral nervous tissue were examined by light and electron microscopy. Hexanedione induced symptoms of peripheral neuropathy such as flaccid weakness, muscular atrophy, and areflexia. Clioquinol intoxicated dogs had a stiff legged gait and hyperreflexia, but showed no signs of muscular atrophy. Dogs given hexanedione developed giant axonal swellings in tissues of the central nervous system (CNS) and the peripheral nervous system (PNS). The changes occurred initially in the distal axons of the long CNS pathways. The swellings contained masses of 10 nanometer neurofilaments and occasional clusters of neurotubules, mitochondria, and smooth endoplasmic reticulum. Clioquinol induced distal axonal degeneration that was confined to the optic tract and long spinal tracts. Oligodendrocytes occurring within empty myelin sheaths were a common finding in damaged optic nerves. No PNS damage was detected. The authors conclude that clioquinol and hexanedione both induce distal axonal degeneration in dogs. The axonal neuropathy induced by clioquinol is confined to selected tracts of the CNS and does not involve the PNS, whereas hexanedione causes a widespread distal axonal degeneration in both the CNS and PNS.
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; In-vivo-studies; Laboratory-animals; Histopathology; Clinical-symptoms; Central-nervous-system; Peripheral-nervous-system;
Author Keywords: Intoxication; Dog; Clioquinol; 2,5-hexanedione; Distal axonopathy
Pathology Albert Einstein Coll of Med 1300 Morris Park Avenue Bronx, N Y 10461
Neurotoxic Disorders; Neurotoxic-effects
Yeshiva University, New York, New York