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1.
Hepatic and extrahepatic microsomal electron transport components and mixed-function oxygenases in the marine fish Stenotomus versicolor. 总被引:1,自引:0,他引:1
NADPH-cytochrome c reductase, benzo[a]pyrene hydroxylase and aminopyrine demethylase activities in hepatic microsomes from the marine fish scup (Stenotomus versicolor) were characterized according to dependence of Ph, temperature, ionic strength and Mg2+. The kinetic properties of benzo[a] pyrene hydroxylase were variable, depending on protein and substrate concentration, with measured Km values for benzo[a]pyrene between 4 × 10?7 M and 4 × 10?5 M. The Km for aminopyrine was 7 × 10?4 M, and NADPH-cytochrome c reductase had Km values of 2.1 × 10?5 M and 1.3 × 10?5 M for cytochrome c and NADPH. respectively. NADH supported benzo[a]pyrene hydroxylation at 10 per cent of the rate seen with NADPH, and no synergism was observed. Aminopyrine demethylation proceeded at least as well with NADH as with NADPH, and there was synergism when combined. NADPH- and NADH-cytochrome c reductases were detected in “microsomes” from fourteen extrahepatic tissues, including kidney, testis, foregut, gill, heart, red muscle, hindgut, buccal epidermis, pyloric caecum, spleen, brain, lens, ovary and white muscle. Benzo[a]pyrene hydroxylase was detected in all but white muscle, while cytochrome P-450 and aminopyrine demethylase were detectable in fewer tissues. Reduced, CO-ligated absorption maxima in the Soret region were 450 nm for all those but liver (occasionally 449 nm) and heart (about 447 nm). The estimated turnover numbers for benzo[a]pyrene hydroxylase and aminopyrine demethylase, and the influence of 7,8-benzoflavone in vitro on benzo[a]pyrene hydroxylase indicate that the cytochromes P-450 in different fish tissues are not catalytically equivalent. 相似文献
2.
Studies were performed on the oxidative biotransformation of benzo[a]pyrene in fortified preparations of human placental microsomes by analysis with high-pressure liquid chromatography. These investigations revealed that the utilization of substrate concentrations (1–2 × 10?4m) sufficiently high to assure zero-order reaction kinetics (in terms of the generation of phenolic metabolites) produced a marked inhibitory effect on the formation of dihydrodiols in the same reaction mixtures. Relative quantities of dihydrodiols generated increased with decreasing substrate concentrations between 200 and 2.7 μm. Additions of manganese or ferric ions to reaction mixtures altered the ratios of generated phenols to dihydrodiols but did not provide an explanation for the differences observed in the literature. Identical results were obtained with either 14C- or 3H-labeled benzo[a]pyrene as substrates. The data suggested the possibility that considerable quantities of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene, a proximate mutagen/carcinogen, may be generated in vivo by placental tissues of women who smoke. 相似文献
3.
《Drug and chemical toxicology》2013,36(4):313-327
ABSTRACTBenzo(a)pyrene metabolism in human placental microsomes from smokers was studied. Benzo(a)pyrene metabolites were separated using high pressure liquid chromatographic technique. Reaction of benzo(a)pyrene with a microsomal fraction of placenta from individuals who smoke cigarettes during pregnency yields 7,8 dihydroxy benzo(a)pyrene as a major metabolite, while 3′-hydroxy benzo(a)pyrene, 4,5 dihydroxy benzo(a)pyrene and quinones constitute minor metabolites. The activities of arylhydrocarbon hydroxylase and 7-ethoxycoumarine deethylase exhibited much higher activities in smokers than in nonsmokers. Examination of specific binding of monoclonal antibodies to cytochrome P-450 isozymes in placental microsomes revealed that cigaratte smoking specifically enhanced the level of cytochrome P-450 c and d isozymes in human placental microsomes. Coincubation of 3H-benzo(a)pyrene and calf thymus DNA with placental microsomes yielded acid insoluble 3H-B(a)P from smokers, suggesting that cigarette smoking may induce placental enzymes which convert benzo(a)pyrene into ultimate metabolites to form carcinogen-DNA adducts. 相似文献
4.
Clinical observations have suggested that elevated levels of theophylline may occur during the use of macrolide antibiotics. In the present study, the plasma clearance of theophylline was studied in rabbits treated with troleandomycin or erythromycin (400 mg · kg?1 · day?1) over a 10-day period. The elimination of theophylline was impaired significantly after 10 days of antibiotic treatment. No change in theophylline elimination occurred when the antibiotics were given for shorter periods of time. Protein, cytochrome P-450 and cytochrome b5 levels, and aminopyrine N-demethylase and benzo[α]pyrene hydroxylase activities were unchanged in hepatic microsomes prepared from rabbits treated with antibiotics for 10 days. Pretreatment of rabbits for 10 days with troleandomycin completely abolished production of 1-methyluric acid from theophylline in isolated hepatic microsomes, but production of 1,3-dimethyluric acid was unaffected. Troleandomycin, when added in vitro to microsomes, had no direct effect on theophylline metabolism. It is concluded that long-term treatment with troleandomycin selectively blocks or destroys one pathway of theophylline metabolism. This mechanism may explain the clinically observed interaction between theophylline and the macrolide antibiotics. 相似文献
5.
The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hepatic microsomal mixed function oxidase (MFO) enzyme systems were examined in female rats. Although TCDD had little effect on NADPH-cytochrome c reductase activity and cytochrome P-450 content, the activities of the cytochrome P-448-mediated enzymes benzo[α]pyrene hydroxylase, ethoxyresorufin O-deethylase, and biphenyl 2-hydroxylase were greatly increased. Three months after a single oral dose of 2 μg/kg TCDD, the cytochrome P-450 content and benzo[α]pyrene hydroxylase and ethoxyresorufin O-deethylase activities were still significantly increased. In addition, the microsomal metabolism of the novel substrate 4,4′-dimethylbiphenyl was greatly increased by TCDD pretreatment. Low dose studies revealed that the ED50 of TCDD induction of benzo[α]pyrene hydroxylase was 0.63 μg/kg and the lowest dose of TCDD which caused a significant increase in enzyme activity was 0.002 μg/kg. Studies in which [1,6-3H]TCDD was used to determine the extent of hepatic uptake of orally administered TCDD at the lowest effective dose of 0.002 μg/kg lead to the estimate that only 65 molecules of TCDD per hepatocyte were required to produce a measurable increase in benzo[α]pyrene hydroxylation. These results attest to the specificity and persistence of TCDD in the induction of cytochrome P-448-mediated enzyme activities in rat liver. The small number of molecules required to induce benzo[α]pyrene hydroxylase suggests that TCDD is among the most potent MFO-inducing agents yet demonstrated in mammalian liver. 相似文献
6.
Hepatic microsomes obtained from control rainbow trout showed relatively low monooxygenase activities toward benzo[a]pyrene, ethoxycoumarin, ethoxyresorufin, and ethylmorphine as substrates. However, benzo[a]pyrene hydroxylation, ethoxycoumarin-O-deethylation, and ethoxyresorufin-O-deethylation were greatly induced by pretreatment of trout with β-naphthoflavone and Aroclor 1242. No increase in ethylmorphine-N-demethylation, liver/body ratio, or yield of microsomal protein were observed. Phenobarbital pretreatment of trout failed to affect any of the parameters studied. The λmax of carboxyferrocytochrome P-450 was at 449 nm in control microsomes, and although a small (40%) increase in total hemoprotein(s) P-450 was seen after β-naphthoflavone pretreatment no hypsochromic shift of the λmax was observed. No significant changes in the ratio of the EtNC ligand spectra were noted after induction. Type I and Type II binding spectra were observed in all microsomal preparations examined. The use of specific inhibitors of monooxygenation (α-naphthoflavone and metyrapone) indicated that control and induced trout hepatic hemoprotein(s) P-450 were similar to rat cytochrome P1-450. Furthermore, sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated the presence of a novel hemoprotein in hepatic microsomes after pretreatment of trout with β-naphthoflavone or Aroclor 1242. This induced protein had a molecular weight of approximately 57,000. 相似文献
7.
The in vitro DNA binding of benzo[a]pyrene metabolites generated by mouse liver microsomes can be resolved into at least nine distinct peaks by elution of a Sephadex LH20 column with a water-methanol gradient. These peaks, representing metabolite-nucleoside complexes, are named A (most polar) through I (least polar). 3-Methylcholanthrene, 2,3,7,8-tetrachlorodibenzo-p-dioxin, phenobarbital, Aroclor 1254, pregnenolone-16α-carbonitrile, or ethanol was administered in vivo to genetically “responsive” C57BL/6N or “nonresponsive” DBA/2N mice, in an attempt to understand and identify increases or decreases in reactive BP intermediates that bind to DNA. Rises or falls in these peaks are also noted when liver microsomes from control or 3-methylcholanthrene-treated C57BL/6N or DBA/2N mice were incubated in vitro with [3H]benzo[a]pyrene and microsomal enzyme inhibitors such as α-naphthoflavone, metyrapone or cyclohexene oxide. All of our interpretations concerning the binding of metabolites to DNA are consistent with non-K-region oxygenation of benzo[a]pyrene being mediated predominantly by cytochrome(s) P1-450 and K-region oxygenation of benzo[a]pyrene being catalysed predominantly by form(s) of P-450 other than P1-450. All of the biological perturbations are consistent with the following assignments. The major reactive intermediate of benzo[a]pyrene contributing to each peak is suggested to be: peaks A and C, an unknown dihydrodiol oxide; peaks B, D, F and I, quinones oxygenated further (or quinone-derived free radicals); peak E, both cis- and tans-7,8-diol-9,10-epoxides; peak F′, the 7.8-oxide; peak G, the 4.5-oxide; and peak H, an unknown phenol oxide. The DNA nucleosides are not identified in this study. Of the ten peaks listed here, it is of interest that the major metabolite(s) contributing to eight of the peaks (all except peaks F' and G) involve(s) more than a single mono-oxygenation by forms of cytochrome P-450. All peaks, with the exception of peak G, appear to be predominantly associated with benzo[a]pyrene metabolism mediated by P1-450 and, therefore, controlled by the Ah locus. The use of these microsomal enzyme inducers or inhibitors—combined with the underlying genetic predisposition of the individual, tissue, or cell culture system under study—demonstrates that the balance between P-450 and epoxide hydrase, and the ratio of each form of P-450 to the other forms of P-450, can influence markedly the quantity and quality of reactive intermediates of benzo[a]pyrene that bind to DNA. 相似文献
8.
The in vitro effects of polycyclic aromatic hydrocarbons (PAHs) on two plasmatic immune parameters, lysozyme concentration and haemolytic alternative complement activity, of the European sea bass, Dicentrarchus labrax, were tested using field (10?7 and 10?9 mg mL?1) and high concentrations (10?3 and 10?5 mg mL?1) observed during oil spills. Peripheral blood from 105 fish was collected, centrifuged at 1200g, for 10 min, at 4 °C and three plasma pools, each of 35 fish, were constituted. Two oils (heavy fuel oil and light cycle oil) and 16 pure PAHs, selected on the basis of the American Environmental Protection Agency list (US EPA), were tested in vitro on the two humoral immune parameters. Only three pure PAHs (anthracene, chrysene and dibenz[a,h]anthracene) modulated lysozyme concentration. Acenaphthene, acenaphthylene, anthracene, benzo[a]anthracene, benzo[a]pyrene, benzo[b]fluoranthene, benzo[k]fluoranthene, pyrene and light cycle oil modified the haemolytic alternative complement activity after 4 h of incubation. This study investigates the direct effects of several PAHs on fish humoral immune functions and describes the haemolytic complement activity of fish as suitable biomarkers of oil pollution. 相似文献
9.
The widely used muscarinic receptor ligand [3H]quinuclidinyl benzilate ([3H]QNB) was found to bind in a site-specific but artifactual manner to rat intestinal mucus, obscuring specific binding to muscarinic receptors on intestinal epithelial cells. Atropine inhibited [3H]QNB binding to mucus with an apparent IC50 of 2.1 × 10?7 M, compared to an IC50 of 1.4 × 10?8 M obtained with a homogenate of intestinal epithelial cells. Unlabeled QNB also inhibited binding of [3H]QNB to mucus but the apparent IC50(4 × 10?7 M) was about 300-fold greater than the IC50 determined with a control tissue, heart muscle (IC50, 1.2 × 10?9M). [3H]QNB binding was saturable over the concentration range of 1–7 nM in the heart, with an apparent kD of 0.76 nM. As expected from the high IC50 for QNB in the mucus binding experiments, binding to mucus was not saturable over the 1–15 nM concentration range. Based on pH profiles and temperature dependency of binding, it seems unlikely that mucin, the primary component of mucus, was responsible for [3H]QNB binding to the mucus. The findings have implications for studies which involve binding of [3H]QNB in particular and other ligands in general to mucus-secreting epithelial tissues. 相似文献
10.
Robert C. Smith Herbert Y. Meltzer Ramesh C. Arora John M. Davis 《Biochemical pharmacology》1977,26(15):1435-1439
Phencyclidine inhibited uptake in vitro of [3H]norepinephrine (ic50 0.52 μM), [3H]dopamine (ic50 0.73 μM) and [3H]serotonin (ic50 0.80 μM) in crude synaptosomal preparations from rat brain through a competitive mechanism. Phencyclidine was fairly similar in potency to d-amphetamine and methylphenidate in inhibiting catecholamine uptake but was 8 times more potent than d-amphetamine and 34 times more potent than methylphenidate in inhibiting [3H]serotonin uptake. 相似文献
11.
Aortic aryl hydrocarbon hydroxylase (EC 1.14.14.2), a cytochrome P-450-dependent mono-oxygenase complex potentially important in the etiology of atherosclerosis, was detected previously in aortic homogenates of humans, monkeys and rabbits [M. R. Juchau, J. A. Bond and E. P. Benditt, Proc. natn. Acad. Sci. U.S.A.73, 3723 (1976)]. The present study more fully characterizes the mono-oxygenase activity in aortas of treated and untreated New Zealand White rabbits. A 2-fold activation was obtained with NADH (7 × 10?4 M) at saturating concentrations of NADPH. Addition of heme (9 μm) increased the enzymatic activity 2- to 4-fold during a 15-min incubation and over 25-fold during a 2-hr incubation. The results suggest the presence of relatively high concentrations of apoprotein in the aortic tissues. Kinetic studies in the presence of heme yielded an apparent Km of 1 × 10?4 M and Vmax of 15.24 pmoles/mg of protein/min with respect to NADPH. A sigmoidal curve was obtained with varying benzo[a]pyrene concentrations (0.5 to 80 μM), suggesting the possibility of allosterism. Aroclor 1254,3-methylcholanthrene and 5,6-benzoflavone acted to induce the cytochrome P-450-dependent mono-oxygenase, while pheno-barbital and pregnenolone 16α-carbonitrile demonstrated little, if any, induction capacity. Analyses of metabolites formed in induced aortas with high-pressure liquid chromatography revealed the formation (in each case) of primarily the phenolic metabolites of benzo[a]pyrene. 相似文献
12.
Pretreatment with either pyrogallol, tropolone or 8-hydroxyquinoline enhanced markedly the mean stereotyped behavior scores after apomorphine treatment in the rat. Experiments in vitro, using rat liver or brain catechol-O-methyltransferase (COMT) preparations and 14C-methyl-S-adenosyl-l-methionine, demonstrated that apomorphine was methylated by this enzyme system. The apparent Km values for dopamine and apomorphine were 2.6 × 10?4 M and 1.4 × 10?3 M, respectively, for liver COMT. Pyrogallol and tropolone inhibited the methylation of apomorphine in vitro competitively when the apomorphine concentration was varied. These results suggest that methylation by COMT may represent an important metabolic pathway for the deactivation of apomorphine in vivo. 相似文献
13.
Human placental microsomes prepared by conventional methods were compared with analogous preparations from adult, male rat livers with respect to biochemical components and systems which could affect rates of mixed-function oxidation and reduction of drugs and steroids in vitro. Each of the electron transport components required for the mixed-function oxidation of drugs in hepatic systems was present in lower concentrations in placental than hepatic microsomes. In contrast to hepatic microsomes, placental microsomes which exhibited unusually high aryl hydrocarbon hydroxylase activities did not contain increased concentrations of the electron transport components. Evidence was provided to indicate that rapid degradation of initial electron donors (reduced pyridine nucleotides) was not responsible for the observance of low or negligible drug metabolic activities observed in incubations with placental micro-somes. Cytochromes P-450 and b5 and their corresponding reductases were shown to be present in human placental preparations. NADPH and NADH-dependent cytochrome c reductase activities in placental microsomes were somewhat lower but comparable to those determined in hepatic preparations. However, cytochromes b5 and P-450 and contaminating hemoglobin and methemoglobin accounted for less than 56 per cent of the total heme present in placental microsomes. Rapid degradation of placental cytochrome P-450 was observed at 37° in the presence of sodium hydrosulfite, but conversion to cytochrome P-420 was minimal after incubation for 1 hr in the presence of NADPH at the same temperature. It was con- sidered probable that the low rates of drug biotransformation observed would be explicable in terms of high substrate specificities of the placental enzymic components. 相似文献
14.
Giorgio Belvedere Haruko Miller Kostas P. Vatsis Minor J. Coon Harry V. Gelboin 《Biochemical pharmacology》1980,29(12):1693-1702
The catalytic activities of hepatic microsornes from untreated, phenobarbital-treated and 3-methylcholanthrene-treated adult rabbits with respect to benzo[a]pyrene hydroxylation and the activation of (?)(rflw-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene[(?)trans-7,8-diol] to DNA-binding metabolites were determined in the absence and presence of mixed-function oxidase inhibitors and compared to the corresponding activities of the individual enzyme systems. Treatment of rabbits with phnobarbital led to induction of P-450LM2 and a concomitant 3-fold enhancement in microsomal benzo[a]pyrene hydroxylase activity, whereas the conversion of (?)trans-7,8-diol to DNA-binding products was unaffected. Homogeneous phenobarbital-inducible P-450LM2 exhibited the highest activity and specificity toward benzo[a]pyrene and the lowest activity toward (?)trans-7,8-diol. Conversely, P-450LM4 was the major form of cytochrome P-450 induced in rabbit liver by 3-methylcholanthrene or β-naphthoflavone, and this was associated in microsomes with an increase in the metabolism of (?)trans-7, 8-diol but not of benzo[a]pyrene. Homogeneous P-450LM4 preferentially Catalyzed the oxygénation of (?)trans-7,8-diol, but was largely ineffective with benzo[a]pyrene. Partially purified P-450LM7 lacked substrate specificity, for it metabolized both benzo[a]pyrene and (?)trans-7, S-diol at comparable rates. Additionally, 7,8-benzoflavone strongly inhibited benzo[a]pyrene hydroxylation by P-450LM4 and phenobarbital-induced microsomes, as well as (?)trans-7,8-diol metabolism by P-450LM4 and 3-methyl-cholanthrene-induced microsomes; in contrast, the activity of control microsomes with either substrate, and the activities of P-450LM4 and LM2 with benzo[a]pyrene and (?)trans-7 ,8-diol, respectively, were only partially or slightly decreased by 7,8-benzoflavone. Unlike 7,8-benzoflavone, butylated hydroxytoluene inhibited benzo[a]pyrene hydroxylation only. Thus, different forms of rabbit liver microsomal cytochrome P-450 were involved in the metabolism of benzo[a]pyrene and its 7,8-dihydrodiol. The results also demonstrate that the changes in substrate specificity and inhibitor sensitivity seen in phenobarbital- and 3-methylcholanthrene-induced microsomes relative to control rabbit liver microsomes can be accounted for by the catalytic properties of a specific form of cytochrome P-450 that prevails in these preparations, P-450LM2 and LM4, respectively. 相似文献
15.
The metabolism of caffeine was investigated in liver slices of young and adult rats. Liver slices from adult male rats metabolized caffeine at an initial rate of 48.31 ± 3.71 nmoles · (g liver)?1 · hr?1 to four main metabolite fractions. By a combination of thin-layer radiochromatography and high performance liquid chromatography, theophylline, paraxanthine and 1, 3, 7-trimethyldihydrouric acid were identified as caffeine metabolites. Apparent Vmax of the overall reaction was 83.30 nmoles caffeine metabolites formed · (g liver)?1 · hr?1. Theophylline competitively inhibited caffeine metabolism [the apparent Km was 19.20, μM in the absence of theophylline, the apparent ki was 36.50 μM in the presence of theophylline (100 μM)]. SKF 525-A inhibited caffeine metabolism; the formation of all of the metabolite fractions was inhibited to a similar extent. Allopurinol (100 μM) had no effect. The specific activity of the enzyme system was extremely low when liver slices of 2-day-old-rats were used [1.46 ± 0.08 nmoles caffeine metabolites formed · (g liver)?1 · hr?1]; the reaction velocity increased gradually with increasing age and reached a peak [52.26 ± 1.41 nmoles caffeine metabolites formed · (g liver)?1 · hr?1]at 30 days of age. Changes in the formation of the four metabolite fractions with age followed the pattern of the overall caffeine metabolism. These results demonstrate that the liver of the newborn rat has an extremely limited capacity to metabolize caffeine in vitro and are consistent with the proposed involvement of the liver microsomal cytochromes P-450 monooxygenase system in the metabolism of caffeine. N-Demethylation is the main pathway of in vitro caffeine metabolism in the rat liver at all ages. 相似文献
16.
The antitumor agent, ellipticine (5,11-dimethyl-6H-pyrido[4-3,b]carbazole) is mainly hydroxylated in position 9 by liver microsomes of differently pretreated rats, this result being in agreement with that obtained previously in vivo. A quick and reliable fluorometric assay, based on the differential fluorescent properties of ellipticine and 9-hydroxyellipticine, is described for the measurement of the 9-hydroxylase activity of different microsomes. This activity exhibits the usual features of the cytochrome-P450-dependent monooxygenases. Control rat liver microsomes exhibit a good affinity for ellipticine (Km = 3 × 10?5 M) but a low specific activity (0.1 nmole min?1 mg protein ?1), perhaps related with an excess substrate inhibition. Pretreatment of rats with benzo[a]pyrene or ellipticine enhances the rate of 9-hydroxylation: pretreatment with phenobarbital does not. Metyrapone and 7,8 benzofiavone are poor inhibitors of ellipticine hydroxylation particularly in microsomes from benzo[a]pyreneor ellipticine-pretreated rats. 相似文献
17.
The in vitro effect of cordydepin was tested using various protein kinase preparations. These included cyclic AMP-dependent protein kinase (A-PK) from bovine heart, cyclic GMP-dependent protein kinase (G-PK) from fetal guinea pig lung, and two cyclic nucleotide-independent nuclear protein kinases (PK-I and PK-II) prepared from rat hepatoma 3924A and rat liver. The 50 per cent inhibitory concentrations (id50) of cordycepin for A-PK and G-PK ranged from 1.5–5.0 × 10?4M and 2.5–8.0 × 10?4 M, respectively, depending on the presence or absence of cyclic AMP and cyclic GMP in the assay. The id50 of cordycepin with either hepatoma 3924A or rat liver PK-I and PK-II was 4.5 × 10?5 M and 1.0 × 10?3 M. respectively. The inhibitory effect of cordycepin was competitive with respect to ATP in all cases. The K{m} for ATP was increased 3-fold and 5-fold by 5 × 10?4 M cordycepin for G-PK and A-PK, respectively, while the Km for ATP was increased 10-fold and 4-fold by 1 × 10?3 M cordycepin for PK-I and PK-II, respectively. 相似文献
18.
Gladen BC Zadorozhnaja TD Chislovska N Hryhorczuk DO Kennicutt MC Little RE 《Human & experimental toxicology》2000,19(11):597-603
Concentrations of chrysene, benz [a] anthracene, benzo [a]-pyrene, benzo [b] fluoranthene, indeno [1,2,3-c,d] pyrene, dibenz [a,h] anthracene, and benzo [g,h,i] perylene were measured in placentas from 200 women from two cities in Ukraine, Kyiv and Dniprodzerzhinsk. The participants had no special exposures and were chosen from among subjects in an ongoing study of reproductive health. All seven of the polycyclic aromatic hydrocarbons (PAHs) were found in all placentas, with the sole exception of benzo [a] pyrene in one placenta. Chrysene was present at the highest concentrations, with median 1.38 ng/g dry weight. Dibenz [a,h] anthracene and benzo [g,h,i] perylene had the lowest concentrations; each had median 0.73 ng/g dry weight. Concentrations in Kyiv were slightly higher than those in Dniprodzerzhinsk, but the difference was significant only for dibenz [a,h] anthracene. Dibenz [a,h] anthracene and benzo [g,h,i] perylene increased significantly with maternal body mass index, but other PAHs showed no such pattern. Placentas from deliveries in autumn or winter had slightly but not significantly higher concentrations. Concentrations were not related to maternal age. There were too few smokers in the sample for meaningful evaluation. No associations were seen between any of the placental PAH concentrations and birth weight of the infant. 相似文献
19.
《Xenobiotica; the fate of foreign compounds in biological systems》2013,43(12):893-902
1. Liver homogenates from rats injected with 3 -methylcholanthrene were employed for metabolism of benzo[a]pyrene (BP) and in assays of aryl hydrocarbon hydroxylase (AHH) activity in vitro.2. Sodium selenite inhibited AHH activity to a maximum of ~70%. It suppressed the overall metabolism of benzo[a]pyrene; a distinct reduction in the products was evident on h.p.l.c. analysis.3. Sodium thiosulphate also inhibited AHH activity by ~ 47%. Inclusion of S2O2-3 and SeO2-3, in combination, led to a cumulative inhibition of 87%.4. The mutagenicity of BP in the Salmonella auxotroph reversion system (Ames test) was enhanced by SeO2-3 at concentrations below 0.2 mM. Above this level a significant anti-mutagenic effect was observed. 相似文献
20.
Prem S. Chaudhry José Cabrera Hector R. Juliani Shambhu D. Varma 《Biochemical pharmacology》1983,32(13):1995-1998
The inhibition of human lens aldose reductase by flavonoids has been studied. Quercetin, the major pentahydroxyflavone, was observed to inhibit human lens aldose reductase by 50% at a concentration of 5 × 10?6 M. The inhibitory activity of its 3-O-glucoside was similar to that of the parent aglycon. Glycosidation with l-sugar (quercitrin and guaijaverin), however, inproved the inhibitory activity (the IC50 values being 1 × 10?6 M and 2.5 × 10?6 M respectively). The improvement in inhibitory activity with glycosidation with l-sugar was also apparent from the high inhibitory activity of myricitrin as compared to myricetin, although the improvement in this case of hexahydroxy flavone glycosidation was significantly less than in the case of penthahydroxy flavone glycosidation. The structure-activity relationship observed for human lens enzyme was similar to that reported previously for rat lens enzyme. Inhibitory activity on the whole however, was lower with human lens enzyme. Some known inhibitors of cyclo-oxygenase such as indomethacin, aspirin and sulindac also inhibited human lens aldose reductase. Thus, an inhibitor of one of the enzymes may actually inhibit both and. when administered, may exert mixed physiological effects. 相似文献