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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-6-13
pubmed:abstractText
Clenbuterol (CLB) is an antiasthmatic drug used also illegally as a lean muscle mass enhancer in both humans and animals. CLB and amine-related drugs in general are nitrosatable, thus raising concerns regarding possible genotoxic/carcinogenic activity. Oral administration of CLB raises the issue of its possible transformation by salivary nitrite at the acidic pH of gastric juice. In acidic human saliva CLB was rapidly transformed to the CLB arenediazonium ion. This suggests a reaction of CLB with salivary nitrite, as confirmed in aerobic HNO(2) solution by a drastic decrease in nitric oxide, nitrite, and nitrate. In human saliva, both glutathione and ascorbic acid were able to inhibit CLB arenediazonium formation and to react with preformed CLB arenediazonium. The effect of ascorbic acid is particularly pertinent because this vitamin is actively concentrated within the gastric juice. EPR spin trapping experiments showed that preformed CLB arenediazonium ion was reduced to the aryl radical by ascorbic acid, glutathione, and serum albumin, the major protein of saliva. As demonstrated by anti-CLB antibodies and MS, the CLB-albumin interaction leads to the formation of a covalent drug-protein adduct, with a preference for Tyr-rich regions. This study highlights the possible hazards associated with the use/abuse of this drug.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0891-5849
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
124-35
pubmed:meshHeading
pubmed-meshheading:18440320-Adrenergic beta-Agonists, pubmed-meshheading:18440320-Amino Acid Sequence, pubmed-meshheading:18440320-Animals, pubmed-meshheading:18440320-Blotting, Western, pubmed-meshheading:18440320-Chromatography, High Pressure Liquid, pubmed-meshheading:18440320-Clenbuterol, pubmed-meshheading:18440320-Electron Spin Resonance Spectroscopy, pubmed-meshheading:18440320-Gastric Juice, pubmed-meshheading:18440320-Humans, pubmed-meshheading:18440320-Hydrogen-Ion Concentration, pubmed-meshheading:18440320-Molecular Sequence Data, pubmed-meshheading:18440320-Nitro Compounds, pubmed-meshheading:18440320-Nitrosation, pubmed-meshheading:18440320-Saliva, pubmed-meshheading:18440320-Serum Albumin, Bovine, pubmed-meshheading:18440320-Spectrophotometry, pubmed-meshheading:18440320-Stomach
pubmed:year
2008
pubmed:articleTitle
Formation of an adduct by clenbuterol, a beta-adrenoceptor agonist drug, and serum albumin in human saliva at the acidic pH of the stomach: evidence for an aryl radical-based process.
pubmed:affiliation
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, 00161 Roma, Italy. pietraf@iss.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural