Abstract. Three adult Beagle dogs given pyridoxine hydrochloride orally at a dose of 150 mg/kg body weight/day for about 100 days developed ataxia and had spastic, dysmetric leg movements. Ultrastructural alterations in the dorsal funiculus of the spinal cord were degeneration and loss of axons and myelin, and secondary changes of the myelin sheaths. Possible pathogenic mechanisms of pyridoxine neurotoxicity are discussed.Pyridoxine (pyridoxol) is one form of vitamin B6, a group of water-soluble, structurally related compounds that also includes pyridoxal and pyridoxamine. These forms are about equally active in supporting animal life and are readily interconvertible 121. Pyridoxal kinase converts these compounds to the phosphorylated coenzyme form.Pyridoxine deficiency has been studied and reviewed extensively [4, 12, 181. Deficiency of vitamin Bs may be caused by absence of this vitamin in the diet or by compounds that interfere with the vitamin. Signs of deficiency in man and in animals include decreased basal metabolic rate and weight gain, microcytic hypochromic anemia, and neurologic abnormalities.The recent interest in megavitamin therapy has resulted in the use of large therapeutic doses of pyridoxine for a variety of conditions. The toxicity of pyridoxine is low [ 171 and, possibly because of a lack of practical significance until now, it has received little study. The subcutaneous lethal dose of pyridoxine hydrochloride for fifty percent of rats is 3.7 g/kg body weight [17]. Affected rats had tonic convulsions and impairment of righting reflexes. The acute and subacute toxicities of excess pyridoxine hydrochloride in dogs resulted in clinical disease characterized by ataxia, and degenerative histologic lesions in spinal and trigeminal ganglia, dorsal roots, the dorsal funiculus, trigeminal nerve fibers and some fascicles of peripheral nerves [ 1,7, 111. Sensory denervation of the plantar lumbrical muscle spindles has been reported with pyridoxine neuropathy in the rat [9].This report extends the study of pyridoxine neurotoxicity to the fine-structural changes in the central nervous system.
