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• W2169713042 abstract "Lathyrism, a human neurological disorder has been linked to the excessive consumption of a plant toxin, β-oxalylamino-l-alanine (l-BOAA) present in Lathyrus sativus. The present study was carried out to elucidate the biochemical mechanisms underlying l-BOAA-induced toxic insult. Incubation of sagittal slices of mouse brain with l-BOAA resulted in dose and time-dependent inhibition of mitochondrial NADH-dehydrogenase (NADH-DH). Significant inhibition of NADH-DH was seen following incubation of brain slices with very low concentration of l-BOAA (0.1 pM). l-BOAA also induced lactate dehydrogenase (LDH) leakage from the slice into the medium in dose-dependent manner. The inhibition of NADH-DH preceded LDH leakage from the slices into the medium. l-BOAA had no effect on other mitochondrial enzymes, namely, isocitrate dehydrogenase or cytochrome c oxidase. Incubation of isolated mouse brain mitochondria with l-BOAA also resulted in inhibition of NADH-DH. l-BOAA-induced inhibition of NADH-DH was prevented by non-N-methyl-d-aspartate (non-NMDA) glutamate receptor antagonists in general and α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist (NBQX) in particular. Other glutamate agonists examined namely, N-methyl-d-aspartate, β-N-methylamino-l-alanine (l-BMAA), l-glutamic acid, N-acetylaspartylglutamate (NAAG), quisqualic acid, kainic acid or AMPA did not have any effect on NADH-DH activity in slices although they induced LDH leakage from the slice into the medium. Incubation of brain slices with l-BOAA did not induce lipid peroxidation or changes in glutathione levels. Prior incubation of slices with glutathione (GSH) or GSH-isopropyl ester did not prevent l-BOAA-induced inhibition of NADH-DH. However, incubation of isolated mitochondria with l-BOAA in the presence of GSH-isopropyl ester prevented l-BOAA-induced inhibition of NADH-DH, indicating the protective effect of mitochondrial glutathione in the prevention of l-BOAA-induced toxicity." @default.
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• W2169713042 date "1993-09-01" @default.
• W2169713042 modified "2023-10-14" @default.
• W2169713042 title "l-BOAA induces selective inhibition of brain mitochondrial enzyme, NADH-dehydrogenase" @default.
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• W2169713042 doi "https://doi.org/10.1016/0006-8993(93)90109-z" @default.
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