THE SUBACUTE NEUROTOXICITY OF EXCESS PYRIDOXINE HCL AND CLIOQUINOL IN BEAGLE DOGS

DENNIS MERLE HOOVER, Purdue University

Abstract

This study was conducted to evaluate clinical, clinicopathologic and pathologic effects of excess orally administered pyridoxine HCl and clioquinol, alone and in combination, when given to adult Beagle dogs for 100 to 112 days. Ten dogs received pyridoxine (150 mg/kg body weight/day), 13 dogs received clioquinol (200 mg/kg body weight/day), 13 dogs received pyridoxine HCl (150 mg/kg body weight/day) plus clioquinol (200 mg/kg body weight/day) and 11 dogs were controls. Four dogs in each of the clioquinol-treated and pyridoxine plus clioquinol-treated groups were killed early in the study due to neurologic disease and/or severe debilitation. One dog given both compounds was found comatose and died on the 3rd test day. Anorexia and loss of body weight occurred in the first weeks of the trial period in dogs in each treatment group and was particularly severe in dogs given both compounds. The dogs later increased their food consumption and body weight stabilized, but the lost body weight was not regained. Certain dogs in each treatment group (10 of 10 pyridoxine-treated, 6 of 13 clioquinol-treated and 12 of 13 pyridoxine plus clioquinol-treated) developed neurologic disease, characterized principally by ataxia. The earliest onset was the 23rd, 18th, and 19th days in pyridoxine, clioquinol and pyridoxine plus clioquinol-treated groups, respectively, and occurred in other dogs in the groups at varying times throughout the remainder of the study period. Dogs given pyridoxine had proprioceptive loss involving fore and hind quarters characterized by stiff, spastic, dysmetric leg movements. Clioquinol-treated dogs had dysmetric leg movements and failure to support body weight in the hind quarters and the fore limbs were involved only in severely affected dogs. The neurologic disease in dogs given both compounds was variable, as clinical signs in some dogs were as seen in the pyridoxine-treated dogs and in other dogs the clinical signs resembled those observed in the clioquinol-treated dogs. Numbers of erythrocytes, concentrations of hemoglobin and packed cell volumes were reduced in dogs in each treatment group and were lowest in dogs given both compounds. Plasma protein values were mildly reduced in dogs given pyridoxine or pyridoxine plus clioquinol, but values of dogs given only clioquinol were similar to controls. Little or no differences were present in the leukocyte counts, blood urea nitrogen concentrations, activities of serum alanine aminotransferase and asparate aminotransferase, or concentrations of sodium, chloride or potassium in treated groups as compared to the control dogs. Pyridoxine-treated dogs had degenerative changes in the dorsal funiculus, spinal tracts of the trigeminal nerves and some fascicles of peripheral nerves. Neurons in spinal ganglia had minimal to mild degenerative changes. Clioquinol-treated dogs had prominent degenerative changes in the dorsal funiculus and optic tracts and minimal to mild degenerative changes in the corticospinal tracts. The peripheral nervous system of clioquinol-treated dogs was not affected. Dogs given both compounds had degenerative changes in a distribution which represented a combination of the areas affected in dogs given only pyridoxine or only clioquinol. The combined effect of pyridoxine and clioquinol was considered additive. Ultrastructural alterations in the dorsal funiculi of pyridoxine and clioquinol-treated dogs and in the optic nerves of clioquinol-treated dogs were characterized by axonal degeneration with secondary changes in myelin and glia.

Degree

Ph.D.

Subject Area

Veterinary services

COinS