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.
References
1.
AntopolW.TarlovI.M.:
Experimental study of the effects produced by large doses of vitamin B6.
J Neuropathol Exp Neurol1:
330–336,
1942.
2.
BrinM.:
Vitamin B6—Chemistry, absorption, metabolism, catabolism and toxicity.
In:
Human Vitamin B6 Requirements—Proceedings of a Workshop,
pp. 1–20.
National Academy of Sciences,
Washington,
1978.
3.
CohenP.A.SchneidmanK.Ginsberg-FellnerF.SturmanJ.A.KnittleJ.GaullG.E.:
High pyridoxine diet in the rat: possible implications for megavitamin therapy.
J Nutr103:
143–151,
1973.
4.
DakshinamurtiK.:
B vitamins and nervous system function.
In:
Nutrition and the Brain,
ed. WurtmanWurtman,
pp. 249–318,
vol. 1.
Raven Press,
New York,
1977.
5.
EtoK.TakahashiY.HoshinoM.SakuraiT.MatsudaM.:
Effect of pyridoxal administration on the contents of pyridoxal phosphate and γ-aminobutyric acid in mouse brain.
J Nutr Sci Vitaminol24:
255–262,
1978.
6.
HiranoA.:
The pathology of the central myelinated axon.
In:
The Structure and Function of Nervous Tissue,
ed. Bourne,
pp. 73–162,
vol. 5.
Academic Press,
New York,
1972.
7.
HooverD.M.CarltonW.W.:
The subacute neurotoxicity of excess pyridoxine HCl and clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) in Beagle dogs. II.
Pathology. Vet Pathol18:
757–768.
8.
JacobsJ.M.MillerR.H.WhittleA.CavanaghJ.B.:
Studies on the early changes in acute isoniazid neuropathy in rats.
Acta Neuropathol47:
85–92,
1979.
9.
KrinkeG.HeidJ.BittigerH.HessR.:
Sensory denervation of the plantar lumbrical muscle spindles in pyridoxine neuropathy.
Acta Neuropathol43:
213–216,
1978.
10.
LiT.LumengL.VeitchR.L.:
Regulation of pyridoxal 5′-phosphate metabolism in liver.
Biochem Biophys Res Commun16:
677–684,
1974.
11.
PhillipsW.E.J.MillsJ.H.L.CharbonneauS.M.TryphonasL.HatinaG.V.ZawidzkaZ.BryceF.R.MunroI.C.:
Subacute toxicity of pyridoxine hydrochloride in the Beagle dog.
Toxicol Appl Pharmacol44:
323–333,
1978.
12.
RobinsonF.A.:
Pyridoxine (Vitamin B6).
In:
The Vitamin Co-Factors of Enzyme Systems,
pp. 328–395.
Pergamon Press,
Oxford,
1966.
13.
SpectorR.:
Vitamin B6 transport in the central nervous system: in vitro studies.
J Neurochem30:
889–897,
1978.
14.
SpectorR.:
Vitamin B6 transport in the central nervous system: in vivo studies.
J Neurochem30:
881–887,
1978.
15.
SpectorR.GreenwaldL.L.:
Transport and metabolism of vitamin B6 in rabbit brain and choroid plexus.
J Biol Chem253:
2373–2379,
1978.
16.
SpencerP.S.SchaumburgH.H.:
Pathobiology of neurotoxic axonal degeneration.
In:
Physiology and Pathobiology of Axons,
ed. Waxman,
pp. 265–282.
Raven Press,
New York,
1978.
