ABSTRACT
The root bark of Anisophyllea dichostyla R. Br. is traditionally used in the Democratic Republic Congo for the treatment of several conditions such as anorexia, fatigue and intestinal infections. We have identified and quantitated several polyphenol antioxidants in the methanol extract of the root bark (120g). The polyphenol content (3.32g/kg) was predominantly ellagitannins (25%) and polyhydroxyflavan-3-ols (catechins and procyanidins, 75%) with 3'-O-methyl-3,4-methylenedioxo ellagic acid 4'-O-beta-d-glucopyranoside and (-)-epicatechin as the major species in each class. These two compounds and the following species were identified unequivocally by NMR spectroscopy: (+)-catechin, (-)-epicatechin 3-O-gallate, 3-O-methyl ellagic acid, 3,3'-di-O-methyl ellagic acid, 3'-O-methyl-3,4-methylenedioxo ellagic acid, 3'-O-methyl-3,4-methylenedioxo ellagic acid 4'-O-beta-d-glucopyranoside, and 3'-O-methyl ellagic acid 4-O-beta-d-xylopyranoside. The following additional compounds were purified by semi-preparative HPLC and tentatively identified on the basis of UV spectra, HPLC-ESI-MS and nano-ESI-MS-MS: (+)-catechin-3-O-beta-d-glucopyranoside, epicatechin-(4beta-->8)-catechin (procyanidin B(1)), epicatechin-(4beta-->8)-epicatechin (procyanidin B(2)), an (epi)catechin trimer, 3-O-methyl ellagic acid 4-O-beta-d-glucopyranoside, (-)-epicatechin 3-O-vanillate, 3,4-methylenedioxo ellagic acid 4'-O- beta-d-glucopyranoside, and 3,3'-di-O-methyl ellagic acid 4-O-beta-d-xylopyranoside. Fractionation of the raw extract by column chromatography on silicic acid yielded 10 fractions. In the hypoxanthine/xanthine oxidase antioxidant assay system, CC-9 which contained a range of polyphenols dominated by (-)-epicatechin-O-gallate proved to be the most potent antioxidant fraction (IC(50)=52 micro g/mL) in terms of ROS scavenging. In terms of XO inhibition CC-8, dominated by (epi)catechin trimer and which also contained appreciable amounts of 3'-O-methyl ellagic acid 4'-O-beta-d-xylopyranoside, as well as the catechins (+)-catechin-3-O-beta-d-glucopyranoside, epicatechin-(4beta-->8)-catechin (procyanidin B(1)), and (-)-epicatechin 3-O-gallate, proved to be the most potent (IC(50)=36 micro g/mL).
Subject(s)
Catechin/chemistry , Cucurbitaceae , Ellagic Acid/chemistry , Phytotherapy , Proanthocyanidins/chemistry , Democratic Republic of the Congo , Humans , Medicine, African Traditional , Plant Extracts/chemistry , Plant RootsABSTRACT
Linseeds are a rich source of lignans, secondary plant substances which are suggested to possess chemopreventive effects inter alia with regard to breast cancer. In a randomised controlled trial 40 German women were informed about "5-a-day" and encouraged to increase their dietary intake of fruit and vegetables. Moreover 19 participants were randomly assigned to an intervention group supplemented with ground linseeds (20 g/d) over a 2-month period. Before and after intervention, urine and blood samples were collected after an overnight fast. Analysis was by intention-to-treat and the outcome parameters of interest were enterolignan concentrations. After linseed supplementation, enterolignan concentrations (mean) measured as their glucuronides by a newly developed high performance liquid chromatography electrospray mass spectrometry (HPLC-ESI-MS) in serum (122 nmol/l) as well as in urine (72 micromol/l) showed a significant increase (P<0.01) compared to pre-intervention values (47 nmol/l and 29 micromol/l). In the control group enterolignan levels were raised slightly but did not reach significance. Serum and urinary enterolignans of the whole collective showed a good pairwise correlation.
Subject(s)
Lignans/blood , Lignans/urine , Linseed Oil/pharmacology , Adult , Butylene Glycols/analysis , Chromatography, High Pressure Liquid , Diet , Dietary Supplements , Female , Fruit , Germany , Glucosides/analysis , Humans , Linseed Oil/chemistry , Middle Aged , Spectrometry, Mass, Electrospray Ionization , VegetablesABSTRACT
In this study the content of anacardic acids, cardanols and cardols in cashew apple, nut (raw and roasted) and cashew nut shell liquid (CNSL) were analysed. The higher amounts (353.6 g/kg) of the major alkyl phenols, anacardic acids were detected in CNSL followed by cashew fibre 6.1 g/kg) while the lowest (0.65 g/kg) amounts were detected in roasted cashew nut. Cashew apple and fibre contained anacardic acids exclusively, whereas CNSL also contained an abundance of cardanols and cardols. Cashew nut (raw and roasted) also contained low amounts of hydroxy alkyl phenols. Cashew nut shell liquid was used for a basic fractionation of the alkyl phenol classes and the individual anacardic acids, major cardanols and cardols were purified to homogeneity from these fractions by semi-preparative HPLC and definitively identified by nano-ESI-MS-MS, GC-MS and NMR analyses. The hexane extracts (10 mg/ml) of all cashew products tested plus CNSL, displayed significant antioxidant capacity. Cashew nut shell liquid was the more efficient (inhibition=100%) followed by the hexane extract of cashew fibre (94%) and apple (53%). The antioxidant capacity correlated significantly (P<0.05) with the concentration of alkyl phenols in the extracts. A mixture of anacardic acids (10.0 mg/ml) showed the higher antioxidant capacity (IC50=0.60 mM) compared to cardols and cardanols (IC50>4.0 mM). The data shows that of these substances, anacardic-1 was by far the more potent antioxidant (IC50=0.27 mM) compared to cardol-1 (IC50=1.71 mM) and cardanol-1 (IC50>4.0 mM). The antioxidant capacity of anacardic acid-1 is more related to inhibition of superoxide generation (IC50=0.04 mM) and xanthine oxidase (IC50=0.30 mM) than to scavenging of hydroxyl radicals. At present a substantial amount of cashew fibre is mostly used in formulations of animal or poultry feeds. The data presented in this study, indicates that this waste product along with CNSL, both of which contain high contents of anacardic acids, could be better utilized in functional food formulations and may represent a cheap source of cancer chemopreventive agents.
Subject(s)
Anacardium/chemistry , Antioxidants/chemistry , Phenols/chemistry , Anacardic Acids/chemistry , Anacardic Acids/isolation & purification , Antioxidants/isolation & purification , Chromatography, High Pressure Liquid , Deoxyguanosine/chemistry , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Gas Chromatography-Mass Spectrometry , Indicators and Reagents , Magnetic Resonance Spectroscopy , Phenols/isolation & purification , Resorcinols/chemistry , Resorcinols/isolation & purification , Spectrometry, Mass, Electrospray Ionization , Superoxides/chemistry , Xanthine Oxidase/antagonists & inhibitorsABSTRACT
A method involving the coupling of high-performance liquid chromatography with electrospray ionisation mass spectrometry (HPLC-ESI-MS) for the quantitative determination of the mammalian lignans enterolactone and enterodiol in human blood and urine has been developed. In contrast to techniques previously published, the method allows direct measurement of free enterolignans as well as their monoglucuronide conjugates in human biofluids with minimal sample preparation. Thereby the method is suitable for large-scale intervention, case-control and epidemiologic studies. Comprehensive, high-precision (1)H and (13)C nuclear magnetic resonance data (CD3OD as solvent) obtained at 11.7 T in combination with polarimetric data show that the major form of lignan precursor in the linseeds used is (-)-secoisolariciresinol diglucoside ((2R,3R)-2,3-bis(4'-hydroxy-3'-methoxy-benzyl)-1,4-butanediyl-bis-beta-d-glucopyranoside) which is transformed by human intestinal bacteria into (+)-enterodiol and (+)-enterolactone. However, these metabolites are mono-glucuronidated after absorption and are detected as (-)-enterodiol 3'-beta-d-glucuronide=(2R,3R)-2-(3'-O-(beta-d-glucopyranosyluronic acid)benzyl)-3-(3''-hydroxybenzyl)-butane-1,4,diol and (-)-enterolactone 3'-beta-d-glucuronide=(2R,3R)-2-(3'-O-(beta-d-glucopyranosyluronic acid)benzyl)-3-(3''-hydroxybenzyl)-beta-butyrolactone in blood and urine.
Subject(s)
Flax/chemistry , Lignans/analysis , Chromatography, High Pressure Liquid , Fermentation , Gas Chromatography-Mass Spectrometry , Glucuronides , Humans , Lignans/blood , Lignans/urine , Reference Standards , Seeds/chemistry , Spectrometry, Mass, Electrospray IonizationABSTRACT
Although it is already known that Tamarind (Tamarindus indica L.) seeds contain phenolic substances, the individual components of the seeds have not been fully identified and quantitated, and in the case of Tamarind pericarp not reported. Therefore, major polyphenolic compounds were extracted using organic solvents and the metabolites were isolated by semi-preparative high performance liquid chromatography. Their structures were elucidated by liquid chromatography-electrospray-ionisation-mass spectrometry (LC-ESI-MS), nano-electrospray-ionisation mass spectrometry (ESI-MS), and where possible by gas chromatography-mass spectrometry (GC-MS) and 1H and 13C NMR. Quantitative analysis of polyphenolic compounds in Tamarind seeds and pericarp was conducted by analytical high performance liquid chromatography (HPLC), calculated against standard curves of authentic compounds. The yields of total phenolic compounds after Soxhlet extraction with methanol were 6.54 and 2.82 g/kg (dry weight) in the seeds and pericarp respectively. The profile (%) of polyphenolics in Tamarind pericarp was dominated by proanthcyanidins (73.4) in various forms (+)-catechin (2.0), procyanidin B2 (8.2), (-)-epicatechin (9.4), procyanidin trimer (11.3), procyanidin tetramer (22.2), procyanidin pentamer (11.6), procyanidin hexamer (12.8) along with taxifolin (7.4), apigenin (2.0), eriodictyol (6.9), luteolin (5.0) and naringenin (1.4) of total phenols, respectively. The content of Tamarind seeds comprised only procyanidins, represented (%) mainly by oligomeric procyanidin tetramer (30.2), procyanidin hexamer (23.8), procyanidin trimer (18.1), procyanidin pentamer (17.6) with lower amounts of procyanidin B2 (5.5) and (-)-epicatechin (4.8). Extraction of Tamarind pericarp and seeds using acetone:methanol:acetic acid gave only procyanidin oligomers, but in much higher yield and variety. The antioxidant capacities of the Soxhlet methanolic extracts were determined, and indicates that Tamarind may be an important source of cancer chemopreventive natural products in tropical regions.
Subject(s)
Antioxidants/chemistry , Phenols/chemistry , Tamarindus/chemistry , Antioxidants/isolation & purification , Biflavonoids/chemistry , Biflavonoids/isolation & purification , Catechin/chemistry , Catechin/isolation & purification , Chromatography, High Pressure Liquid , Deoxyguanosine/chemistry , Fruit/chemistry , Gas Chromatography-Mass Spectrometry , Magnetic Resonance Spectroscopy , Phenols/isolation & purification , Plant Extracts/chemistry , Proanthocyanidins/chemistry , Proanthocyanidins/isolation & purification , Seeds/chemistry , Spectrometry, Mass, Electrospray Ionization , Tannins/chemistry , Tannins/isolation & purification , Xanthine Oxidase/chemistryABSTRACT
14C-D,L-verapamil was administered intravenously (10 mg) and orally (80 mg) to five volunteer patients. Plasma concentrations of verapamil, which were determined by mass fragmentography, declined bi-exponentially with half-lives of the chi-phase ranging from 18 to 35 min and of the beta-phase from 170 to 440 min. The apparent volume of distribution ranged from 270 to 460 litre and plasma clearance from 730 to 1980 ml/min. Following oral administration absorption was almost complete as judged from the area under the curve (AUC) of 14C-activity and cumulative urinary excretion of 14C. After intravenous infusion of verapamil about 80% of the radioactivity administered could be recovered in urine and faeces within 5 d. Despite its almost complete absorption after oral administration verapamil was shown to undergo extensive first pass metabolism as the bioavailability was only 10 to 22%. Rapid biotransformation had occurred as only a small percentage of AUC of 14C was seen to correspond to unchanged verapamil after both intravenous and oral administration.
Subject(s)
Verapamil/metabolism , Administration, Oral , Aged , Biological Availability , Feces/analysis , Half-Life , Humans , Injections, Intravenous , Male , Middle Aged , Protein Binding , Verapamil/administration & dosage , Verapamil/bloodABSTRACT
The highly polymorphic N-acetyltransferases (NAT1 and NAT2) are involved in both activation and inactivation reactions of numerous carcinogens, such as tobacco derived aromatic amines. The potential effect of the NAT genotypes in individual susceptibility to lung cancer was examined in a hospital based case-control study consisting of 392 Caucasian lung cancer patients [152 adenocarcinomas, 173 squamous cell carcinomas (SCC) and 67 other primary lung tumours] and 351 controls. In addition to the wild-type allele NAT1*4, seven variant NAT1 alleles (NAT1*3, *10, *11, *14, *15, *17 and *22) were analysed. A new method based on the LightCycler (Roche Diagnostics Inc.) technology was applied for the detection of the polymorphic NAT1 sites at nt 1088 and nt 1095. The NAT2 polymorphic sites at nt 481, 590, 803 and 857 were detected by polymerase chain reaction-restriction fragment length polymorphism or LightCycler. Multivariate logistic regression analyses were performed taking into account levels of smoking, age, gender and occupational exposure. An increased risk for adenocarcinoma among the NAT1 putative fast acetylators [odds ratio (OR) 1.92 (1.16-3.16)] was found but could not be detected for SCC or the total case group. NAT2 genotypes alone appeared not to modify individual lung cancer risk, however, individuals with combined NAT1 fast and NAT2 slow genotype had significantly elevated adenocarcinoma risk [OR 2.22 (1.03-4.81)] compared to persons with other genotype combinations. These data clearly show the importance of separating different histological lung tumour subtypes in studies on genetic susceptibility factors and implicate the NAT1*10 allele as a risk factor for adenocarcinoma.
Subject(s)
Arylamine N-Acetyltransferase/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Genetic Predisposition to Disease , Isoenzymes/genetics , Lung Neoplasms/genetics , Polymorphism, Genetic , Aged , Base Sequence , Case-Control Studies , DNA Primers , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Restriction Fragment LengthABSTRACT
Polymorphic glutathione-S-transferase (GST) genes causing variations in enzyme activity may influence individual susceptibility to lung cancer. In this case-control study (consisting of 389 Caucasian lung cancer patients, including 151 adenocarcinomas (ACs) and 172 squamous cell carcinomas (SCCs), and 353 hospital control subjects without malignant disease, genotype frequencies for GSTM1, GSTM3, GSTP1 and GSTT1 were determined by polymerase chain reaction (PCR)/ restriction fragment length polymorphism (RFLP)-based methods. While adjusted odds ratios (ORs) indicated no significantly increased risk for lung cancer overall due to any single GST genotype, the risk alleles for GSTM1, GSTM3 and GSTP1 conferring reduced enzyme activity were present at higher frequency in SCC than in AC patients. This is consistent with a reduced detoxification of carcinogenic polycyclic aromatic hydrocarbons (PAHs) from cigarette smoke that are more important for the development of SCC than for AC. An explorative data analysis also identified statistically significantly increased ORs for the combinations GSTT1 non-null and GSTP1 GG or AG for lung cancer overall (OR 2.23, CI 1.11-4.45), and for SCC (OR 2.69, CI 1.03-6.99). For lung cancer overall, and especially among SCC patients, the GSTT1 null genotype was underrepresented (SCC 11.2% v. control subjects 19%, P = 0.026, OR 0.57, CI 0.30-1.06). Additionally, in 28 patients with hamartomas, the GSTT1 null genotype was also protective (P = 0.013), while GSTP1 variant allele carriers were overrepresented (OR 2.48, CI 1.06-6.51). In conclusion, GST genotypes may act differently, either by detoxifying harmful tobacco carcinogens and/or by eliminating lung cancer chemopreventive agents. The latter role for GSTT1 would explain the observed lower risk of SCC and hamartoma associated with GSTT1 null. Further confirmatory studies are required.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Genetic Predisposition to Disease , Glutathione Transferase/genetics , Hamartoma/genetics , Lung Diseases/genetics , Lung Neoplasms/genetics , Adenocarcinoma/enzymology , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/enzymology , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/enzymology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Case-Control Studies , Female , Gene Frequency , Genotype , Glutathione S-Transferase pi , Hamartoma/enzymology , Hamartoma/pathology , Humans , Isoenzymes/genetics , Lung Diseases/enzymology , Lung Diseases/pathology , Lung Neoplasms/enzymology , Lung Neoplasms/pathology , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, GeneticABSTRACT
The half-life, peak concentration, peak accumulation and tissue availability of the DNA-crosslinking nitrosourea 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine (CNC-alanine) and its oestradiol-linked derivate (CNC-alanine-oestradiol-17-ester) were studied in liver, lung, spleen, uterus and mammary carcinomas in female Sprague-Dawley rats with chemically induced mammary carcinomas. Compared with CNC-alanine, the ester had a longer half-life, higher peak concentration, increased peak accumulation and enhanced tissue availability in all tissues. In oestradiol receptor positive mammary carcinomas, the oestradiol-linked drug showed a 2 times higher peak concentration, a 5 times longer half-life, a 10 times increased peak accumulation and a 20 times greater tissue availability compared with CNC-alanine. Oestradiol-linked nitrosoureas may offer new perspectives for site-directed chemotherapy of oestradiol receptor positive breast cancer.
Subject(s)
Antineoplastic Agents/pharmacokinetics , Estradiol/analogs & derivatives , Mammary Neoplasms, Experimental/drug therapy , Nitrogen Mustard Compounds/pharmacokinetics , Alanine/analogs & derivatives , Alanine/pharmacokinetics , Alanine/therapeutic use , Animals , Antineoplastic Agents/therapeutic use , Estradiol/pharmacokinetics , Estradiol/therapeutic use , Female , Nitrogen Mustard Compounds/therapeutic use , Rats , Rats, Inbred Strains , Tissue DistributionABSTRACT
In our ongoing studies on the chemoprevention of cancer we have a particular interest in the health benefits of the Mediterranean diet, of which olive oil is a major component. Recent studies have shown that extravirgin olive oil contains an abundance of phenolic antioxidants including simple phenols (hydroxytyrosol, tyrosol), aldehydic secoiridoids, flavonoids and lignans (acetoxypinoresinol, pinoresinol). All of these phenolic substances are potent inhibitors of reactive oxygen species attack on, e.g. salicylic acid, 2-deoxyguanosine. Currently there is growing evidence that reactive oxygen species are involved in the aetiology of fat-related neoplasms such as cancer of the breast and colorectum. A plausible mechanism is a high intake of omega-6 polyunsaturated fatty acids which are especially prone to lipid peroxidation initiated and propagated by reactive oxygen species, leading to the formation (via alpha,beta-unsaturated aldehydes such as trans-4-hydroxy-2-nonenal) of highly pro-mutagenic exocyclic DNA adducts. Previous studies have shown that the colonic mucosa of cancer patients and those suffering from predisposing inflammatory conditions such as ulcerative colitis and Crohn's disease generates appreciably higher quantities of reactive oxygen species compared with normal tissue. We have extended these studies by developing accurate high performance liquid chromatography (HPLC) methods for the quantitation of reactive oxygen species generated by the faecal matrix. The data shows that the faecal matrix supports the generation of reactive oxygen species in abundance. As yet, there is a dearth of evidence linking this capacity to actual components of the diet which may influence the colorectal milieu. However, using the newly developed methodology we can demonstrate that the antioxidant phenolic compounds present in olive oil are potent inhibitors of free radical generation by the faecal matrix. This indicates that the study of the inter-relation between reactive oxygen species and dietary antioxidants is an area of great promise for elucidating mechanisms of colorectal carcinogenesis and possible future chemopreventive strategies.
Subject(s)
Antioxidants/isolation & purification , Breast Neoplasms/prevention & control , Colorectal Neoplasms/prevention & control , Phenols/therapeutic use , Plant Oils/chemistry , Antioxidants/therapeutic use , Chromatography, High Pressure Liquid/methods , Diet , Female , Humans , Magnetic Resonance Spectroscopy/methods , Mass Spectrometry/methods , Olive Oil , Phenols/isolation & purification , Plant Oils/therapeutic use , Reactive Oxygen Species/metabolismABSTRACT
Twenty-seven tropical plants of medicinal importance were analysed for primary and secondary amines by chemiluminescence detection on a Thermal Energy Analyzer (TEA) modified for use on 'nitrogen mode' following derivatization with benzene sulphonyl chloride (BSC) and gas chromatographic (GC) separation of their sulphonamides. Nitrite was determined by colorimetry at 540 nm after diazotization with sulphanilamide and coupling with N-(1-naphthyl)ethylenediamine to form an azo dye. Nitrate was determined as nitrite following on-line reduction by granulated cadmium. Dimethylamine in the range of 0.5 ppm to 18.2 ppm was detected in 96% of samples, while pyrrolidine ranged between 0.7 ppm and 12.78 ppm in 14 samples. Isobutylamine, methylamine and ethylamine were the most ubiquitous primary amines. Largest number of secondary amines (four) was found in Azadirachta indica (Neem) while largest number of primary amines (six) was detected in Azadirachta indica and Tamarindus indica (Tsamiya) which also contained the highest amount of total primary amines (148.8 ppm). Nitrate and nitrite were seldom found in plant extracts whose pH were generally below 7.0. These findings suggests that early exposures to precursors of N-nitroso compounds via medicinal plants might contribute to total risk posed by environmental carcinogens in Nigeria.
Subject(s)
Amines/analysis , Nitroso Compounds , Plants, Medicinal/chemistry , Amines/isolation & purification , Methylamines/analysis , Methylamines/isolation & purification , Morphine/analysis , Morphine/isolation & purification , Nigeria , Pyrrolidines/analysis , Pyrrolidines/isolation & purificationABSTRACT
The in vitro nitrosation of sun-dried red chillies (Capsicum annuum) and of its constituents capsaicin and dihydrocapsaicin was studied. The nitrophenols 4-nitroguaiacol, 4,6-dinitroguaiacol, nitrocapsaicin and nitrodihydrocapsaicin were detected as final products, whereas no formation of nitrosamides was observed though this is expected from the amide precursors capsaicin and dihydrocapsaicin. The nitrosation occurs readily with remarkable yields of nitrophenols even at physiological pH and at nitrite concentrations which are within the range of those found in the human stomach. Due to their toxicity, nitrophenols need to be included in total risk assessment through potential endogenous nitrosation of foodstuffs.
Subject(s)
Capsaicin/analogs & derivatives , Capsaicin/chemistry , Nitrophenols/chemistry , Spices , Chromatography, High Pressure LiquidABSTRACT
The study describes the kinetics of demethylation of mononitrosocaffeidine (MNC), a new asymmetric N-nitrosamine derived from caffeine. The demethylation of its precursor compound caffeidine was also studied. The results presented here suggest (a) that liver microsomes from fasted rats preferentially demethylate the N-methylnitrosamine group in MNC indicating the demethylation by cytochrome P450IIE1, (b) demethylation of MNC shows two apparent Km values, one of 117-166 microM responsible for the demethylation at the N-methylnitrosamino group of MNC, and the other Km of 1.84-2.26 mM for the remaining N-demethylations, (c) in contrast, caffeidine is a low affinity substrate for microsomal demethylation as indicated by a high Km of 14.3-16.3 mM, and (d) the demethylation at amino-N amino-N, and N-1 in both these compounds are mainly catalysed by P450 enzymes induced by Aroclor 1245 in rats.
Subject(s)
Caffeine/analogs & derivatives , Caffeine/metabolism , Microsomes, Liver/metabolism , Mutagens/metabolism , Nitrosamines/metabolism , Nitroso Compounds/metabolism , Animals , Biotransformation , Cytochrome P-450 CYP2E1 , Cytochrome P-450 Enzyme System/metabolism , Fasting , Kinetics , Male , Oxidoreductases, N-Demethylating/metabolism , Rats , Rats, Inbred Strains , Substrate SpecificityABSTRACT
Ten popular brands of cigarettes on the Nigerian market were analyzed for tobacco-specific nitrosamines (TSNA) in tobacco and in mainstream smoke, as well as nitrate in tobacco. TSNA was analyzed using a gas chromatography/thermal energy analyzer (GC-TEA), while nitrate was determined spectrophotometrically as nitrite following on-line reduction with copper, diozatization with sulfanilamide and coupling with N-(1-naphthyl) ethylene diamine to form an azo dye. In mainstream smoke, the concentration of NNN, NAB/NAT and NNK were respectively, between 8 and 90 ng, 10 and 65 ng, and between 15 and 72 ng/cigarette. Preformed NNN ranged between 64 and 565 ng/cigarette, while preformed NAB/NAT and NNK ranged respectively from 109 to 476 ng/cigarette, and from 55 to 317 ng/cigarette. Nitrate levels ranged between 1.5 and 6.1 mg/g tobacco. In general, the results indicate that the TSNA content of Nigerian cigarettes are within the range found for European and American cigarettes.
Subject(s)
Nicotiana/chemistry , Nitrosamines/analysis , Plants, Toxic , Nicotine/analysis , Nigeria , Smoke/analysis , Tars/analysisABSTRACT
Urinary excretion of N-nitrosodimethylamine (NDMA) in Sprague--Dawley rats was investigated after oral administration and inhalation of NDMA and concomitant narcosis by Thalamonal and diethyl ether. While ether anesthesia induced a 4-fold increase in the excretion rate, there was a drastic reduction (about 20-fold) in the amount of NDMA excreted after narcosis by Thalamonal.
Subject(s)
Anesthetics/pharmacology , Dimethylnitrosamine/urine , Droperidol/pharmacology , Fentanyl/pharmacology , Animals , Drug Combinations/pharmacology , Drug Interactions , Female , Male , Rats , Rats, Inbred StrainsABSTRACT
N-Nitrosodiethanolamine (NDE1A) was administered by gavage to male rats in single doses of 1000, 500 and 100 mg/kg body wt. More than 70% of a given dose was excreted unchanged in the urine, essentially within the first 24 h after exposure. This high excretion rate might explain the relatively low carcinogenic potential of NDE1A, and also offers a possible method of monitoring exposure to this compound under occupational and/or environmental conditions.
Subject(s)
Diethylnitrosamine/urine , Nitrosamines/urine , Administration, Oral , Animals , Diethylnitrosamine/administration & dosage , Diethylnitrosamine/analogs & derivatives , Male , Rats , Time FactorsABSTRACT
Salivary nitrate and nitrite levels in a sample population of children and adults from a high risk area of esophageal and gastric cancer in Kashmir are reported. In different age groups mean levels of salivary nitrate/nitrite ranged between 21-36 ppm and 12-17 ppm, respectively.
Subject(s)
Esophageal Neoplasms/epidemiology , Nitrates/analysis , Nitrites/analysis , Saliva/chemistry , Stomach Neoplasms/epidemiology , Adolescent , Adult , Age Factors , Child , Child, Preschool , Diet , Esophageal Neoplasms/etiology , Humans , India , Middle Aged , Nitrates/administration & dosage , Nitrites/administration & dosage , Sampling Studies , Stomach Neoplasms/etiologyABSTRACT
Nitrosatability of dried Nigerian vegetables and spices was investigated under simulated gastric conditions. N-Nitroso-dimethylamine (NDMA) was the only volatile nitrosamine found above the preformed level except in ugwu where N-nitroso-piperidine (2.3 ppb) was also detected. The lowest NDMA value of 0.4 ppb was found in bitterleaf while onions had the highest level (14.7 ppb) of nitrosation. The results suggest that, under endogenous conditions, nitrosation of these foodstuffs could be an important contributory factor in cancer aetiology.
Subject(s)
Nitrosamines/metabolism , Vegetables/metabolism , Food Preservation/methods , Gastric Juice/metabolism , In Vitro Techniques , NigeriaABSTRACT
The effect of dietary nitrate on endogenous nitrosation of a therapeutic dose of piperazine has been described in five human volunteers who acted as their own controls. The urinary excretion of endogenously formed N-nitro-somonopiperazine (MNPz) ranged between 9.2 and 80.1 micrograms/24 h on a normal uncontrolled diet which increased from 25.7 to 163.7 micrograms/24 h when the diet was supplemented with 250 mg nitrate. The corresponding urinary nitrate was 63.0-122.7 mg/24 h and 119.2-322.0 mg/24 h, respectively. The dinitroso derivative of piperazine was detected only in trace amounts and no detectable increase in its excretion was observed during high nitrate exposure. The unchanged piperazine (range 294-784 mg/24 h) in urine showed a decrease under high nitrate regimen (range 185-399 mg/24 h).
Subject(s)
Carcinogens/analysis , Diet , Nitrates/metabolism , Nitrosamines/urine , Piperazines/metabolism , Humans , Nitrates/urine , Piperazine , Piperazines/urineABSTRACT
The in vitro metabolism of nitrosodimethylamine (NDMA) was studied in liver tissue obtained from male weanling kwashiorkor wistar rats. The elimination of this compound and that of nitrosomorpholine (NMOR) from the blood, after a single intravenous dose, was also investigated. N-demethylase activity in liver microsomes of the test animals was not significantly different from that of the controls although the activity of this enzyme per gram wet liver tissue was considerably reduced in the model animals. On the other hand, the glutathione (GSH) content in liver cytosol of the kwashiorkor animals was much higher than that of the controls. The elimination of NDMA and NMOR from the blood of the experimental animals over 8 hr following i.v. administration of the carcinogens, showed that the clearance rate of each nitrosamine was significantly lower in the kwashiorkor rats.