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Dose-dependent expression of neuronopathy after experimental pyridoxine intoxication

Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA.

We examined the sequence of nervous system abnormalities that resulted when rats were given excess amounts of vitamin B₆ (pyridoxine). High doses of pyridoxine (1,200 or 600 mg/kg/d) for 6 to 10 days caused a neuronopathy with necrosis of dorsal root ganglion (DRG) sensory neurons, accompanied by centrifugal axonal atrophy and breakdown of peripheral and central sensory axons. Large diameter neurons with long processes and large cytoplasmic volumes were especially affected. Smaller doses (300 to 150 mg/kg/d) for up to 12 weeks had minor effects on DRG neurons, but produced a neuropathy with axonal atrophy and degeneration. Guinea pigs given 1,800 mg/kg/d developed sensory neuronopathy, whereas mice given similar or higher doses did not have neuropathologic abnormalities. Multiple factors including rate of administration, differential neuronal vulnerability, and species susceptibility have bearing on the final expression of pyridoxine neurotoxicity.

Address correspondence and reprint requests to Dr. Sladky, Department of Neurology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104.

Supported by the Muscular Dystrophy Association, CIDA grant #K08-NS01077 to Dr. Sladky, and USPHS center grant NS08075.

Received August 23, 1988. Accepted for publication in final form March 14, 1989.

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