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Synthesis and phototoxicity of isomeric 7,9-diglutathione pyrrole adducts: Formation of reactive oxygen species and induction of lipid peroxidation

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Pyrrolizidine alkaloids (PAs) are hepatotoxic, genotoxic, and carcinogenic in experimental animals. Because of their widespread distribution in the world, PA-containing plants are probably the most common poisonous plants affecting livestock, wildlife, and humans. Upon metabolism, PAs generate reactive dehydro-PAs and other pyrrolic metabolites that
lead to toxicity. Dehydro-PAs are known to react with glutathione (GSH) to form 7-GSH-(þ/)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (7-GS-DHP) in vivo and in vitro and 7,9-diGS-DHP in vitro. To date, the phototoxicity of GS-DHP adducts has not been well studied. In this study, we synthesized 7-GS-DHP, a tentatively assigned 9-GSDHP,
and two enantiomeric 7,9-diGS-DHP adducts by reaction of dehydromonocrotaline with GSH. The two 7,9-diGS-DHPs were separated by high performance liquid chromatography (HPLC) and their structures were characterized by 1H nuclear magnetic resonance (NMR) and 1He1H correlation spectroscopy (COSY) NMR spectral analysis. Photoirradiation
of 7-GS-DHP, 9-GS-DHP, and the two 7,9-diGS-DHPs as well as dehydromonocrotaline,dehydroheliotrine, and the 7-R enantiomer of DHP (DHR), by UVA light at 0 J/cm2, 14 J/cm2,and 35 J/cm2 in the presence of a lipid, methyl linoleate, all resulted in lipid peroxidation in a light dose-responsive manner. The levels of lipid peroxidation induced by the two isomeric 7,9-diGS-DHPs were significantly higher than that by 7-GS-DHP and 9-GS-DHP. When 7,9-diGS-DHP was irradiated in the presence of sodium azide (NaN3), the level of lipid peroxidation decreased; lipid peroxidation was enhanced when methanol was replaced by deuterated methanol. These results suggest that singlet oxygen is a product induced by the irradiation of 7,9-diGS-DHP. When irradiated in the presence of superoxide dismutase (SOD), the level of lipid peroxidation decreased, indicating that lipid peroxidation is also mediated by superoxide. These results indicate that lipid peroxidation is mediated by reactive oxygen species (ROS). These results suggest that 7,9-diGS-DHPs are phototoxic, generating lipid peroxidation mediated by ROS.

Keywords:
7,9-diGS-DHP adducts DHP LC-ES-MS/MS pyrrolizidine alkaloid

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Informasi Detail

Judul Seri

j ournal of food and drug anal ys i s

No. Panggil

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Penerbit

: Elsevier Taiwan., 2015

Deskripsi Fisik

j ournal of food and drug anal ys i s 2 3 ( 2 0 1 5 ) 5 7 7 e5 8 6

Bahasa

English

ISBN/ISSN

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Klasifikasi

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Tipe Isi

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Tipe Media

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Tipe Pembawa

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Edisi

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Subjek

Food And Health

Info Detail Spesifik

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Pernyataan Tanggungjawab

Wati/Agus

Versi lain/terkait

Lampiran Berkas

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