title: Decrease in pyridoxal-5'-phosphate concentration and increase in pyridoxal concentration in rat plasma by 4'-O-methylpyridoxine administration.
abstract: Food poisoning from Ginkgo biloba seeds can cause epilepsy because of a decrease in γ-aminobutyric acid (GABA) concentrations in the brain. We previously demonstrated that 4'-O-methylpyridoxine (MPN) is responsible for this observed toxicity of G biloba seeds; however, the mechanism for the decrease in GABA and plasma concentration profile of MPN has not been clarified. Our hypothesis is that MPN induces a decrease in vitamin B6 concentrations, resulting in a decrease in GABA concentration. This study aimed to characterize the plasma concentration profile of MPN and intrinsic vitamin B6 concentrations (pyridoxal [PL], PL-5'-phosphate [PLP], and 4-pyridoxic acid) using a rat model. Plasma concentrations of B6 vitamers after intravenous MPN administration (5 mg/kg) were determined using high-performance liquid chromatography with a fluorescence detector. The half-life of MPN (0.91 ± 0.05 hours) was shorter in rats than the previously reported value in humans. We found a significant decrease in the plasma concentration of PLP, an active form of vitamin B6, after MPN administration. We also observed an increase in plasma PL and 4-pyridoxic acid concentrations; the increase in PL concentration may be caused by either metabolism of MPN to PL or by MPN-mediated inhibition of PL kinase. The present study is the first in vivo study showing relatively rapid elimination of MPN in rats and a decrease in plasma PLP concentration caused by MPN.
authors.affiliation: Department of Food and Chemical Toxicology, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Hokkaido, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.affiliation: Department of Food and Chemical Toxicology, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Hokkaido, Japan.
authors.forename: Teruki
authors.initials: T
authors.lastname: Yoshimura
authors.affiliation: Department of Food and Chemical Toxicology, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Hokkaido, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Johno
authors.affiliation: Department of Food and Chemical Toxicology, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Hokkaido, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Ishikawa
authors.affiliation: Department of Food and Chemical Toxicology, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Hokkaido, Japan; Laboratory for Molecular and Cellular Biology, Faculty of Pharmacy, Chiba Institute of Science, Choshi-shi, Chiba-ken, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Food and Chemical Toxicology, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Hokkaido, Japan. Electronic address: wadakg@hoku-iryo-u.ac.jp.
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D005517:Foodborne Diseases / Q000378:metabolism; D020441:Ginkgo biloba / Q000009:adverse effects / Q000737:chemistry*; D006801:Humans; D008297:Male; D011730:Pyridoxal / Q000097:blood; D011731:Pyridoxal Kinase / Q000037:antagonists & inhibitors*; D011732:Pyridoxal Phosphate / Q000097:blood* / Q000172:deficiency; D011735:Pyridoxic Acid / Q000097:blood; D011736:Pyridoxine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood; D017208:Rats, Wistar; D012639:Seeds; D026681:Vitamin B 6 Deficiency / Q000097:blood*; D014803:Vitamin B Complex / Q000097:blood; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C406624:4'-O-methylpyridoxine; D014803:Vitamin B Complex; D011730:Pyridoxal; D005680:gamma-Aminobutyric Acid; D011735:Pyridoxic Acid; D011732:Pyridoxal Phosphate; D011731:Pyridoxal Kinase; D011736:Pyridoxine
keywords: Ginkgo biloba; Methylpyridoxine; Pyridoxal kinase; Pyridoxal-5′-phosphate; Vitamin B(6) deficiency