Formation of an adduct by clenbuterol, a β-adrenoceptor agonist drug, and serum albumin in human saliva at the acidic pH of the stomach: Evidence for an aryl radical-based process

Pietraforte, Donatella; Brambilla, G; Camerini, Serena; Scorza, Giuseppe; Peri, Laura; Loizzo, Alberto; Crescenzi, Marco; Minetti, Maurizio

doi:10.1016/j.freeradbiomed.2008.03.018

Cited by 9 publications

(2 citation statements)

References 52 publications

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“…In vitro experiments and MALDI-TOF analysis of the reaction products demonstrate that acid-catalyzed nitrosation of the aniline amino group of clenbuterol and further reaction with albumin yields adducts of the aryl portion with the amino acid side chains, most likely at tyrosine residues (Pietraforte et al, 2008).…”

Section: Pharmaceutical Drugsmentioning

confidence: 99%

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Rubino

Pitton

Fabio

et al. 2009

Mass Spectrometry Reviews

109

170

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Cancer and degenerative diseases are major causes of morbidity and death, derived from the permanent modification of key biopolymers such as DNA and regulatory proteins by usually smaller, reactive molecules, present in the environment or generated from endogenous and xenobiotic components by the body's own biochemical mechanisms (molecular adducts). In particular, protein adducts with organic electrophiles have been studied for more than 30 [see, e.g., Calleman et al., 1978] years essentially for three purposes: (a) as passive monitors of the mean level of individual exposure to specific chemicals, either endogenously present in the human body or to which the subject is exposed through food or environmental contamination; (b) as quantitative indicators of the mean extent of the individual metabolic processing which converts a non-reactive chemical substance into its toxic products able to damage DNA (en route to cancer induction through genotoxic mechanisms) or key proteins (as in the case of several drugs, pesticides or otherwise biologically active substances); (c) to relate the extent of protein modification to that of biological function impairment (such as enzyme inhibition) finally causing the specific health damage. This review describes the role that contemporary mass spectrometry-based approaches employed in the qualitative and quantitative study of protein-electrophile adducts play in the discovery of the (bio)chemical mechanisms of toxic substances and highlights the future directions of research in this field. A particular emphasis is given to the measurement of often high levels of the protein adducts of several industrial and environmental pollutants in unexposed human populations, a phenomenon which highlights the possibility that a number of small organic molecules are generated in the human organism through minor metabolic processes, the imbalance of which may be the cause of "spontaneous" cases of cancer and of other degenerative diseases of still uncharacterized etiology. With all this in mind, it is foreseen that a holistic description of cellular functions will take advantage of new analytical methods based on time-integrated metabolomic measurements of a new biological compartment, the "adductome," aimed at better understanding integrated organism response to environmental and endogenous stressors.

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Section: Pharmaceutical Drugsmentioning

confidence: 99%

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Rubino

Pitton

Fabio

et al. 2009

Mass Spectrometry Reviews

109

170

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“…5 The interaction of nitrite with substances containing functional Ngroups like amine, amide, etc., could generate genotoxic-carcinogenic N-nitroso compounds (NOC) in the gastrointestinal tract. 6,7 NOC are unique among carcinogenic agents in being active in all species and in displaying a broad spectrum of target cells and organs in which they are able to induce cancer. The formation of NOC can occur in food (when preserved with nitrite), in the environment, and in the digestive tract (especially in the stomach, where the presence of HCl favours nitrosation reactions) from nitrosatable precursors and nitrosating agents.…”

Section: Introductionmentioning

confidence: 99%

Reaction mixtures formed by nitrite and selected sulfa-drugs showed mutagenicity in acidic medium

Trossero¹,

Pontoriero²,

Hure³

et al. 2009

Quím. Nova

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Recebido em 29/4/08; aceito em 8/12/08; publicaod na web em 28/5/09Nitrite, which is present in preserved meat and can be produced in the oral cavity by reduction of nitrate taken from vegetables, could react in stomach with nitrosatable drugs, giving genotoxic-carcinogenic N-nitroso compounds (NOC). The mutagenicity of reaction mixtures formed by sodium nitrite and selected sulfa-drugs (sulfathiazole, HST; phtalylsulfathiazole, PhST; complex Co(II)-sulfathiazole, Co(II)-ST) in acidic medium was evaluated using the Salmonella typhimurium reverse mutation assay (Ames test), with TA98 and TA100 strains. The reactions were carried out at room temperature, with a mole ratio [nitrite]/[sulfa-drug] ≥ 1. The three reaction mixtures showed mutagenic effects in the considered range.

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Exposure to Substances via Food Consumption

Abraham

Arcella

Blume

et al. 2019

The Practice of Consumer Exposure Assessment

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Formation of an adduct by clenbuterol, a β-adrenoceptor agonist drug, and serum albumin in human saliva at the acidic pH of the stomach: Evidence for an aryl radical-based process

Cited by 9 publications

References 52 publications

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Reaction mixtures formed by nitrite and selected sulfa-drugs showed mutagenicity in acidic medium

Exposure to Substances via Food Consumption

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