<i>In vitro</i> metabolic fate of alizapride: evidence for the formation of reactive metabolites based on liquid chromatography‐tandem mass spectrometry

Aprile, Silvio; Grosso, Erika Del; Grosa, Giorgio

doi:10.1002/jms.3011

Cited by 2 publications

(1 citation statement)

References 24 publications

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“…Cigarette smoking represents the primary source of acrolein exposure to humans, and mainstream CS contains up to 90 ppm acrolein (Moretto et al, ). In addition, acrolein can be produced endogenously during lipid or amino acid oxidation (Uchida, ), in conditions of inflammation (Anderson et al, ), during oxidative deamination of spermine (Kwak, Kensler, & Casero, ), or drug metabolism (Aprile, Del Grosso, & Grosa, ). A very interesting and useful method was recently published with the aim to highlight protein adducts in human lung epithelial cells (HBE1) after acrolein treatment.…”

Section: In‐gel Proteomics: 1d Separation And/or Mass Spectrometry Tomentioning

confidence: 99%

Pathophysiology of tobacco smoke exposure: Recent insights from comparative and redox proteomics

Colombo

Clerici

Giustarini

et al. 2013

Mass Spectrometry Reviews

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First-hand and second-hand tobacco smoke are causally linked to a huge number of deaths and are responsible for a broad spectrum of pathologies such as cancer, cardiovascular, respiratory, and eye diseases as well as adverse effects on female reproductive function. Cigarette smoke is a complex mixture of thousands of different chemical species, which exert their negative effects on macromolecules and biochemical pathways, both directly and indirectly. Many compounds can act as oxidants, pro-inflammatory agents, carcinogens, or a combination of these. The redox behavior of cigarette smoke has many implications for smoke related diseases. Reactive oxygen and nitrogen species (both radicals and non-radicals), reactive carbonyl compounds, and other species may induce oxidative damage in almost all the biological macromolecules, compromising their structure and/or function. Different quantitative and redox proteomic approaches have been applied in vitro and in vivo to evaluate, respectively, changes in protein expression and specific oxidative protein modifications induced by exposure to cigarette smoke and are overviewed in this review. Many gel-based and gel-free proteomic techniques have already been used successfully to obtain clues about smoke effects on different proteins in cell cultures, animal models, and humans. The further implementation with other sensitive screening techniques could be useful to integrate the comprehension of cigarette smoke effects on human health. In particular, the redox proteomic approach may also help identify biomarkers of exposure to tobacco smoke useful for preventing these effects or potentially predictive of the onset and/or progression of smoking-induced diseases as well as potential targets for therapeutic strategies.

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Section: In‐gel Proteomics: 1d Separation And/or Mass Spectrometry Tomentioning

confidence: 99%

Pathophysiology of tobacco smoke exposure: Recent insights from comparative and redox proteomics

Colombo

Clerici

Giustarini

et al. 2013

Mass Spectrometry Reviews

View full text Add to dashboard Cite

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Identification of urinary metabolites of imperatorin with a single run on an LC/Triple TOF system based on multiple mass defect filter data acquisition and multiple data mining techniques

Qiao

Shi

et al. 2013

Anal Bioanal Chem

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The detection of drug metabolites, especially for minor metabolites, continues to be a challenge because of the complexity of biological samples. Imperatorin (IMP) is an active natural furocoumarin component originating from many traditional Chinese herbal medicines and is expected to be pursued as a new vasorelaxant agent. In the present study, a generic and efficient approach was developed for the in vivo screening and identification of IMP metabolites using liquid chromatography-Triple TOF mass spectrometry. In this approach, a novel on-line data acquisition method mutiple mass defect filter (MMDF) combined with dynamic background subtraction was developed to trace all probable urinary metabolites of IMP. Comparing with the traditionally intensity-dependent data acquisition method, MMDF method could give the information of low-level metabolites masked by background noise and endogenous components. Thus, the minor metabolites in complex biological matrices could be detected. Then, the sensitive and specific multiple data-mining techniques extracted ion chromatography, mass defect filter, product ion filter, and neutral loss filter were used for the discovery of IMP metabolites. Based on the proposed strategy, 44 phase I and 7 phase II metabolites were identified in rat urine after oral administration of IMP. The results indicated that oxidization was the main metabolic pathway and that different oxidized substituent positions had a significant influence on the fragmentation of the metabolites. Two types of characteristic ions at m/z 203 and 219 can be observed in the MS/MS spectra. This is the first study of IMP metabolism in vivo. The interpretation of the MS/MS spectra of these metabolites and the proposed metabolite pathway provide essential data for further pharmacological studies of other linear-type furocoumarins.

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In vitro metabolic fate of alizapride: evidence for the formation of reactive metabolites based on liquid chromatography‐tandem mass spectrometry

Cited by 2 publications

References 24 publications

Pathophysiology of tobacco smoke exposure: Recent insights from comparative and redox proteomics

Pathophysiology of tobacco smoke exposure: Recent insights from comparative and redox proteomics

Identification of urinary metabolites of imperatorin with a single run on an LC/Triple TOF system based on multiple mass defect filter data acquisition and multiple data mining techniques

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