Decrease in pyridoxal-5'-phosphate concentration and increase in pyridoxal concentration in rat plasma by...

Area of Science:

• Neuroscience
• Toxicology
• Biochemistry

Background:

• Ginkgo biloba seed poisoning is linked to epilepsy due to reduced brain GABA concentrations.
• 4'-O-methylpyridoxine (MPN) is identified as the toxic compound in Ginkgo biloba seeds.
• The mechanism by which MPN reduces GABA and its plasma concentration profile remain unclear.

Purpose of the Study:

• To investigate the hypothesis that MPN reduces GABA levels by decreasing vitamin B6 concentrations.
• To characterize the plasma concentration profile of MPN in a rat model.
• To measure intrinsic vitamin B6 concentrations (pyridoxal [PL], PL-5 -phosphate [PLP], and 4-pyridoxic acid) following MPN administration.

Main Methods:

• Rats were administered MPN intravenously at a dose of 5 mg/kg.
• Plasma concentrations of MPN and vitamin B6 vitamers were analyzed using high-performance liquid chromatography with a fluorescence detector.
• Pharmacokinetic parameters, including half-life, were determined.

Main Results:

• MPN exhibited a shorter half-life (0.91 ± 0.05 hours) in rats compared to humans.
• MPN administration led to a significant decrease in plasma PLP, the active form of vitamin B6.
• Plasma concentrations of PL and 4-pyridoxic acid increased, suggesting potential MPN metabolism or inhibition of PL kinase.

Conclusions:

• This is the first in vivo study demonstrating rapid MPN elimination in rats.
• MPN administration causes a reduction in plasma PLP concentrations, supporting the hypothesis of MPN-induced vitamin B6 depletion.
• The findings provide insight into the mechanism of Ginkgo biloba seed neurotoxicity.