Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:34834-67-8 (trans-3'-hydroxycotinine)
 135 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urinary excretion of nicotine and its five major metabolites (nicotine-N-glucuronide, cotinine, cotinine-N-glucuronide, trans-3'-hydroxycotinine, and trans-3'-hydroxycotinine-O-glucuronide), expressed as nicotine equivalents (NE), has been used as a biomarker of smoking-related nicotine exposure. In this open-label, single center study, we investigated the relationship between nicotine retention from smoking and urinary excretion of NE in adult smokers. After a 4-day washout period, 16 adult male smokers smoked 6 cigarettes per day for four consecutive days according to three predefined smoking patterns: no inhalation (Pattern A), normal inhalation (Pattern B), and deep inhalation (Pattern C). The amount of nicotine retained in the respiratory tract during smoking was estimated from the difference between the amounts of nicotine delivered and exhaled. The daily excretion of urinary NE was measured in 24h urine samples by LC-MS/MS. The mean (+/-S.D.) amount of nicotine retained was 0.126+/-0.167, 0.960+/-0.214, and 1.070+/-0.223mg/cig for Patterns A, B, and C, respectively. The mean (+/-S.D.) relative retention (the amount retained relative to the amount delivered) was 11.2+/-14.7%, 98.0+/-1.6%, and 99.6+/-0.3% for Patterns A, B, and C, respectively. On the fourth day of smoking, an average of 86+/-20% of the total daily amount of retained nicotine was recovered as NE in 24h urine. Nicotine equivalents was treated as a single component and the data was described by a first-order elimination pharmacokinetic model which assumed instantaneous input and distribution. Based on this model, the elimination half-life of NE was 19.4+/-2.6h, and the NE excretion had reached approximately 96% of the steady state levels by Day 4. Our results suggest that most of the nicotine inhaled from a cigarette is retained (> or =98%) in the lung, and at steady state, daily urine NE excretion reflects approximately 90% of the retained nicotine dose from cigarette smoking.
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PMID:Respiratory retention of nicotine and urinary excretion of nicotine and its five major metabolites in adult male smokers. 1771 38

This study describes the impact of exposure to secondhand smoke for subjects who spend time in a discotheque, by comparing within-subject baseline and postexposure urinary cotinine levels. A total of 100 nonsmoking volunteers from a central region of Mexico provided a urine sample before entering a discotheque and another sample an average of 6 hr after the end of exposure. Concentrations of cotinine and its metabolite, trans-3'-hydroxycotinine, were measured in the urine by liquid chromatography-mass spectrometry. In females the average preexposure level of urinary cotinine was 2.2 ng/ml, and the average postexposure level was significantly higher, at 15.7 ng/ml. In males the average preexposure level of cotinine was 3.7 ng/ml, compared with 49.1 ng/ml in the postexposure assessment. The highest postexposure values were found in men younger than 22 years old with a value of 469.5 ng/ml. Exposure to secondhand smoke is a serious health risk. Our findings are important given that many of our subjects were exposed to substantial amounts of secondhand smoke in discotheques, as evidenced by the high urinary cotinine and 3'-hydroxycotinine concentrations. These findings support the need to prohibit smoking in discotheques to protect nonsmokers' health.
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PMID:Secondhand smoke exposure in Mexican discotheques. 1785 65

There are no analytical methods that simultaneously quantify nicotine, cotinine, trans-3'-hydroxycotinine, nornicotine and norcotinine in human meconium. Such a method could improve identification of in utero tobacco exposure, determine if maternal dose-meconium concentration relationships exist, and whether nicotine meconium concentrations predict neonatal outcomes. The first liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry method for simultaneous quantification of these analytes in meconium was developed and validated. Specimen preparation included homogenization, enzyme hydrolysis and solid phase extraction. The linear range was 1.25 or 5-500ng/g. Method applicability was evaluated with meconium collected from an in utero tobacco exposed infant.
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PMID:Quantification of nicotine, cotinine, trans-3'-hydroxycotinine, nornicotine and norcotinine in human meconium by liquid chromatography/tandem mass spectrometry. 1824 21

Cytochrome P450 2A6 (CYP2A6) is a human enzyme best known for metabolizing tobacco-related compounds, such as nicotine, cotinine (COT), and nitrosamine procarcinogens. CYP2A6 genetic variants have been associated with smoking status, cigarette consumption, and tobacco-related cancers. Our objective was to functionally characterize four nonsynonymous CYP2A6 sequence variants with respect to their haplotype, allele frequency, and association with in vivo CYP2A6 activity. In vivo, nicotine was administered orally to 281 volunteers of Black African descent. Blood samples were collected for kinetic phenotyping and CYP2A6 genotyping. In vitro, nicotine C-oxidation catalytic efficiencies of heterologously expressed variant enzymes were assessed. The four uncharacterized sequence variants were found in seven novel alleles CYP2A6(*)24A&B ; (*)25, (*)26, (*)27, and *28A&B, most were associated with impaired in vivo CYP2A6 activity. Nicotine metabolism groupings, based on the in vivo data of variant alleles, were created. Mean trans-3'-hydroxycotinine/cotinine (3HC/COT) differed (P<0.001) between normal (100%), intermediate (64%), and slow (40%) groups. Systemic exposure to nicotine following oral administration also differed (P<0.001) between normal (100%), intermediate (139%), and slow (162%) metabolism groups. In addition, alleles of individuals with unusual phenotype-genotype relationships were sequenced, resulting in the discovery of five novel uncharacterized alleles and at least one novel duplication allele. A total of 7% of this population of Black African descent had at least one of the eight novel characterized alleles and 29% had at least one previously established allele. These findings are important for increasing the accuracy of association studies between CYP2A6 genotype and behavioral, disease, or pharmacological phenotypes.
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PMID:Novel and established CYP2A6 alleles impair in vivo nicotine metabolism in a population of Black African descent. 1836 Sep 15

To assess the exposure to tobacco smoke constituents, the biomarkers are used. In most studies conducted among active smokers, the cotinine is usually utilised as such a biomarker. The aim of this study was to estimate an application of determining two nicotine metabolites, cotinine and trans-3'-hydroxycotinine (3-HC) in order to assess cigarette smoking among pregnant women. There were 25 patients (15 smokers, 10 non-smokers) admitted to Delivery Ward in Gynecology and Obstetrics Clinical Hospital of the University of Medical Sciences in Poznan. The free and total form of cotinine and trans-3'-hydroxycotinine in urine were determined by the means of high performance liquid chromatography with spectrometry detection. The results of this studies indicated that in urine both cotinine and trans-3'-hydroxycotinine are conjugated with glucoronide acid in the high degree. The linear correlation between free and conjugated form of cotinine and whole cotinine concentration indicates the possibility of application of all three of them as biomarkers of tobacco smoke exposure. The high conjugation of trans-3'-hydroxycotinine with glucuronic acid (over 80 %), and high correlation between glucuronide and total trans-3'-hydroxycotinine concentration proves necessity of having the urine samples hydrolysed or determining the 3'-hydroxycotinine glucoronide, when application of 3-HC as a biomarker of tobacco smoke exposure is concerned. Our studies confirm other authors' observations that division of 3'-hydroxycotinine and cotinine concentrations might be used as a predictor of differences in cotinine metabolite ratio (polimorphism). The studies shown that using analytical equipment, nowadays available in the most laboratories (HPLC), it is possible to determined two biomarkers which are very useful and give various information, no matter whether they are conjugated with glucuronic acid, or not.
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PMID:[Concentration of cotinine and trans-3'-hydroxycotinine and its glucuronides in urine of smoking pregnant women]. 1840 99

The objectives of this research were to improve and standardize a relatively easy, highly sensitive and highly accurate method of measuring nicotine, cotinine and trans-3'-hydroxycotinine in the urine of non-smokers exposed to environmental tobacco smoke (ETS) and to clarify the reliability of this method. Blinded studies using this analytical method were conducted in two universities. Standard solutions of nicotine, cotinine and trans-3'-hydroxycotinine were prepared at one university, divided in two parts and sent to another two universities for analyses by gas chromatography-mass spectrometry (GC/MS) without revealing the concentrations. It was found that the assay lower limit was at a level that could be used in passive smoking surveys and good results were obtained in crosschecks of samples of unknown concentration between the two universities. Since this method was considered to be useful for analyzing these urinary substances, ETS exposure experiments were performed in three universities using urinary nicotine, cotinine and trans-3'-hydroxycotinine as specific biomarkers of the urine. Non-smokers were exposed to ETS in an exposure room in each university. It was found that the nicotine concentrations in the urine of the subjects exposed to ETS reached a peak at about 2 hours after the end of exposure, which was somewhat later than that in active smokers. Because cotinine and trans-3'-hydroxycotinine in the urine are metabolites of nicotine, it was evident that the quantities were lower and the increasing rates were also less than that of nicotine. When the deceases in nicotine/ creatinine, cotinine/creatinine and trans-3'-hydroxycotinine/creatinine ratios in the urine were calculated using theoretical curves, the half-life times were calculated to be 13.9, 20.0 and 63.0 hours, respectively.
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PMID:Studies on a simultaneous analytical method of urinary nicotine and its metabolites, and their half-lives in urine. 1878 7

Nicotine has been shown to induce endothelial dysfunction, which is an early marker of atherosclerosis. Nicotine undergoes extensive metabolism in the liver, forming a number of major and minor metabolites. There are very limited data on the effect of nicotine metabolites on the cardiovascular system. This study investigates the effects of nicotine and the nicotine metabolites, cotinine, cotinine-N-oxide, nicotine-1'-N-oxide, norcotinine, trans-3'-hydroxycotinine, on angiotensin-converting enzyme (ACE) in human endothelial cells. Cultured endothelial cells obtained from human umbilical cord vein (HUVECs) were stimulated with nicotine or nicotine metabolites in concentrations similar to those observed in plasma during smoking. ACE activity and expression were analyzed using commercial kits. The results showed that nicotine and nicotine metabolites can increase both activity and expression of ACE. However, a marked individual variation in the response to the drugs was observed. This variation was not associated with the ACE insertion/deletion polymorphism. Tobacco contains numerous chemical compounds, and the underlying cause for development of atherosclerosis in smokers is probably multifactorial. The results from this study could explain one cellular mechanism by which smoking exerts negative effect on the vascular system.
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PMID:Effect of nicotine and nicotine metabolites on angiotensin-converting enzyme in human endothelial cells. 1906 15

There has been speculation that the addition of menthol to cigarettes may affect the manner in which cigarettes are smoked, potentially influencing smokers' exposures to smoke constituents that have been associated with smoking-related diseases. One hundred twelve male and female smokers participated in a parallel-arm study to determine whether the ad libitum smoking of menthol cigarettes results in differences in smoke constituent exposure biomarkers in blood and urine relative to those smoking nonmenthol cigarettes having similar machine-measured (Federal Trade Commission) yields of approximately 9 to 10 mg "tar." The study subjects were provided cigarettes of their preferred menthol or nonmenthol types prior to two 24-hour study intervals spaced one week apart. Carboxyhemoglobin levels were measured in blood samples drawn at midafternoon following the two 24-hour urine collection periods. Six urinary nicotine metabolites (nicotine, cotinine, trans-3'-hydroxycotinine and respective glucuronides) were determined as measures of nicotine intake, and urinary 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide were determined to assess exposure to the tobacco-specific nitrosamine 4-(N-nitrosomethylamino)-1-(3-pyridinyl)-1-butanone. Subjects' median blood carboxyhemoglobin values did not differ significantly between the cigarette types. Neither total urinary NNAL nor urinary nicotine equivalents exhibited statistically significant differences between the menthol and nonmenthol cigarette smokers. The present findings indicate that moderately heavy smokers of menthol and nonmenthol cigarettes of similar machine-generated smoke yield exhibit essentially identical levels of biomarkers of smoke constituent exposure. These results are consistent with the substantial majority of epidemiology studies to date that suggest the risks attending the smoking of menthol and nonmenthol cigarettes are similar.
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PMID:Smokers of menthol and nonmenthol cigarettes exhibit similar levels of biomarkers of smoke exposure. 1919 Jan 53

A clinical study, conducted in Germany, compared two methods of estimating exposure to cigarette smoke. Estimates of mouth level exposure (MLE) to nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), pyrene and acrolein were obtained by chemical analysis of spent cigarette filters for nicotine content. Estimates of smoke constituent uptake were achieved by analysis of corresponding urinary biomarkers: for nicotine; total nicotine equivalents (nicotine, cotinine, trans-3'-hydroxycotinine plus their glucuronide conjugates), for NNK; (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) plus glucuronide, for pyrene; 1-hydroxy pyrene (1-OHP) plus glucuronide and for acrolein; 3-hydroxylpropyl-mercapturic acid (3-HPMA) plus the nicotine metabolite cotinine in plasma and saliva. Two hundred healthy volunteer subjects were recruited; 50 smokers of each of 1-2 mg, 4-6 mg and 9-10 mg ISO tar yield cigarettes and 50 non-smokers (NS). Smokers underwent two periods of home smoking, each followed by residence in a clinic. Smoking was permitted ad libitum, and spent cigarette filters, cigarette consumption data, 24h urine, as well as plasma and saliva samples were collected. Significant correlations (p<0.001) were found between MLE and the relevant biomarker for each smoke constituent. The Pearson correlation coefficients (r) were 0.83 (nicotine), 0.76 (NNK), 0.82 (acrolein) and 0.63 (pyrene). Mean MLE estimates for nicotine, NNK and pyrene showed a dose response in line with ISO tar yield smoked, with 10 mg > 4 mg >1 mg, and for acrolein 10 mg> 4 mg > *1mg (where * indicates not significant at 95% confidence level). The mean exposure estimates from biomarkers for nicotine, NNK and acrolein also showed a dose response in line with ISO tar yield with 10 mg > 4 mg > 1 mg > NS, and for pyrene 10 mg > *4 mg> 1 mg> NS. This study shows that estimates of exposure obtained by filter analysis and biomarkers of exposure correlate significantly over a wide range of smoke exposures and that filter analysis may provide a simple and effective alternative to biomarkers for estimating smokers' exposure.
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PMID:A study to estimate and correlate cigarette smoke exposure in smokers in Germany as determined by filter analysis and biomarkers of exposure. 1953 4

Native Hawaiian smokers are at higher risk and Japanese-American smokers at lower risk of lung cancer (LC), compared with white smokers, even after accounting for smoking history. Because variation in carcinogen exposure/metabolism may occur separately of smoking amount, we compared urinary biomarkers of uptake and detoxification of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-a potent lung carcinogen-among 578 smokers in these ethnic/racial groups in Hawaii. We measured the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc) and examined total NNAL (NNAL + NNAL-Gluc) and the NNAL detoxification ratio (NNAL-Gluc:NNAL). Native Hawaiians and Japanese-Americans had lower age- and sex-adjusted mean total NNAL, compared with whites. When further adjusting for urinary nicotine equivalents (the sum of nicotine, cotinine, trans-3'-hydroxycotinine and their respective glucuronides), only the difference between Japanese-Americans and whites was eliminated. Therefore, consistent with their lower LC risk, a lower cigarette smoke exposure explains the lower NNK dose of Japanese-Americans, but it does not explain that of Native Hawaiians. The mean detoxification ratio was also lower in Native Hawaiians and Japanese-Americans, compared with whites, even after adjusting for nicotine equivalents (p < 0.0001). Lower NNAL glucuronidation in Native Hawaiians might contribute to their increased LC risk; however, this is inconsistent with the low glucuronidation ratio similarly observed in the low-risk Japanese-American group and because Native Hawaiians had lower total NNAL levels. Thus, exposure and detoxification of NNK are unlikely to explain, by themselves, the differences in LC risk among the 3 populations studied.
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PMID:Exposure to the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in smokers from 3 populations with different risks of lung cancer. 1959 61


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