首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 46 毫秒
1.
Populations inhabiting metal-impacted freshwater systems located nearby industrial and urban areas may be under intense selection. The present study aims to address two fundamental microevolutionary aspects of metal contamination in the midge Chironomus riparius (Meigen): Are populations inhabiting historically metal contaminated sites genetically adapted to metals? And, are populations from these sites genetically eroded? To answer these questions, C. riparius populations were sampled from three sites with well-known histories of metal contamination and three nearby-located references. Genetic adaptation to metals was investigated through acute and chronic exposures to cadmium (Cd), after rearing all populations for at least six generations under laboratory clean conditions. Genetic diversity was estimated based on the allelic variation of seven microsatellite markers. Results showed higher acute tolerance to Cd in populations originating from metal contaminated sites compared to their respective references and significant differences in two out of three pairwise comparisons. However, there was a mismatch between acute and chronic tolerance to Cd with results of the partial life-cycle tests suggesting fitness costs under control clean conditions in two metal-adapted populations. Despite no evidences of genetic erosion in populations sampled from metal contaminated sites, our results suggest genetically inherited tolerance to Cd in populations inhabiting historically contaminated sites. These findings lend support to the use of C. riparius as a model organism in evolutionary toxicology and highlight the importance of coupling measures of neutral genetic diversity with assessments of chemical tolerance of populations for a better understanding of contaminant-induced adaptation and evolutionary processes.  相似文献   

2.
Cytochrome P450 (CYP) 2D6 is present in less than about 2% of all CYP enzymes in the liver, but it is involved in the metabolism of about 25% of currently used drugs. CYP2D6 is the most polymorphic among the CYP enzymes. We determined alleles and genotypes of CYP2D6 in 3417 Koreans, compared the frequencies of CYP2D6 alleles with other populations, and observed the differences in pharmacokinetics of metoprolol, a prototype CYP2D6 substrate, depending on CYP2D6 genotype. A total of 3417 unrelated healthy subjects were recruited for the genotyping of CYP2D6 gene. Among them, 42 subjects with different CYP2D6 genotypes were enrolled in the pharmacokinetic study of metoprolol. The functional allele *1 and *2 were present in frequencies of 34.6 and 11.8%, respectively. In decreased functional alleles, *10 was the most frequent with 46.2% and *41 allele was present in 1.4%. The nonfunctional alleles *5 and *14 were present at 4.5 and 0.5% frequency, respectively. The *X?×?N allele was present at a frequency of 1.0%. CYP2D6*1/*1, *1/*2 and *2/*2 genotypes with normal enzyme activity were present in 12.1%, 8.6% and 1.4% of the subjects, respectively. CYP2D6*5/*5, *5/*14, and *14/*14 genotypes classified as poor metabolizer were only present in 4, 2, and 1 subjects, respectively. Mutant genotypes with frequencies of more than 1% were CYP2D6*1/*10 (32.0%), *10/*10 (22.3%), *2/*10 (11.7%), *5/*10 (3.7%), *1/*5 (2.5%), and *10/*41 (1.2%). The relative clearance of metoprolol in CYP2D6*1/*10, *1/*5, *10/*10, *5/*10, and *5/*5 genotypes were 69%, 57%, 24%, 14% and 9% of CYP2D6*wt/*wt genotype, respectively. These results will be very useful in establishing a strategy for precision medicine related to the genetic polymorphism of CYP2D6.  相似文献   

3.
The aim of this study was to determine the concentrations of heavy metals (Cd, Pb, Zn, Fe, and Mn) in soil, and their bioavailability and bioaccumulation in Vaccinium myrtillus L. and Vaccinium vitis-idaea L. organs. Analysis also concerned the physiological responses of these plants from three polluted sites (immediate vicinity of a zinc smelter in Miasteczko ?l?skie, ArcelorMittal Poland S.A. iron smelter in D?browa Górnicza-?osień, and Jaworzno III power plant in Jaworzno) and one pseudo-control site (Pazurek nature reserve in Jaroszowiec Olkuski). All of the sites are situated in the southern parts of Poland in the ?l?skie or Ma?opolskie provinces. The contents of proline, non-protein thiols, glutathione, ascorbic acid, and the activity of superoxide dismutase and guaiacol peroxidase in the leaves of Vaccinium myrtillus L. and Vaccinium vitis-idaea L. were measured. In soil, the highest levels of Cd, Pb, and Zn (HNO3 extracted and CaCl2 extracted) were detected at the Miasteczko ?l?skie site. At all sites a several times lower concentration of the examined metals was determined in the fraction of soil extracted with CaCl2. Much higher Cd, Pb, Zn and Fe concentrations were found in V. myrtillus and V. vitis-idaea grown at the most polluted site (located near the zinc smelter) in comparison with cleaner areas; definitely higher bioaccumulation of these metals was found in lingonberry organs. Additionally, we observed a large capability of bilberry to accumulate Mn. Antioxidant response to heavy metal stress also differed between V. myrtillus and V. vitis-idaea. In V. myrtillus we found a positive correlation between the level of non-protein thiols and Cd and Zn concentrations, and also between proline and these metals. In V. vitis-idaea leaves an upward trend in ascorbic acid content and superoxide dismutase activity accompanied an increase in Cd, Pb, and Zn concentrations. At the same time, the increased levels of all tested metals in the leaves of V. vitis-idaea were accompanied by a decreased activity of guaiacol peroxidase. In both species increased Mn accumulation caused a decrease in antioxidant response.  相似文献   

4.
Antioxidative enzymes (superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX)), as well as lipid peroxidation and proline were studied in moss Brachythecium piligerum Card. collected from different sites in Shanghai, China, to validate the physiological parameters as biomarkers of atmospheric heavy metal pollution. Results demonstrated that the responses of POD and CAT activities, as well as MDA and proline contents were in accordance with the heavy metal contents in mosses. That is, POD activity, MDA, and proline content were activated and CAT activity was inhibited in heavier polluted sites, indicating that POD and CAT activities, and MDA and proline contents could be used as biomarkers for biomonitoring atmospheric heavy metal pollution. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2010.  相似文献   

5.
Zolpidem is indicated for the short-term treatment of insomnia and it is predominantly metabolized by CYP3A4, and to a lesser extent by CYP2C19, CYP1A2, and CYP2C9. Therefore, we evaluated the effects of CYP2C19 genetic polymorphisms on the pharmacokinetics of zolpidem in healthy male subjects. Thirty-two male subjects were recruited and all subjects were classified into three groups according to their genotypes: CYP2C19EM (CYP2C19*1/*1, n?=?12), CYP2C19IM (CYP2C19*1/*2 or *1/*3, n?=?10), and CYP2C19PM (CYP2C19*2/*2, *2/*3 or *3/*3, n?=?10). The pharmacokinetic parameters of zolpidem were compared in three CYP2C19 genotype groups after zolpidem administration with or without a CYP3A4 inhibitor at steady-state concentration. Plasma concentrations of zolpidem were determined up to 12 h after drug administration by liquid chromatography-tandem mass spectrometry method. The maximum plasma concentration (Cmax) differed, but mean total area under the plasma concentration–time curve (AUCinf), half-life (t1/2), and apparent oral clearance (CL/F) of zolpidem administered alone did not significantly differ among the three different CYP2C19 genotype groups. Furthermore, when zolpidem was administered with a CYP3A4 inhibitor at steady-state concentration, there were no significant differences in any of the pharmacokinetic parameters of zolpidem in relation to CYP2C19 genotypes. In conclusion, we did not find any evidence for the impact of CYP2C19 genetic polymorphisms on the pharmacokinetic parameters of zolpidem.  相似文献   

6.

Purpose

To evaluate the effects of CYP2C19 and CYP2C9 genotypes on the pharmacokinetic variability of valproic acid (VPA) in epileptic patients using a population pharmacokinetic (PPK) approach.

Methods

VPA concentrations were measured in 287 epileptic patients, who were genotyped for CYP2C19*2/*3 and CYP2C9*3. Patients who were on monotherapy with VPA were divided into two groups, a PPK-model group (n?=?177) and a PPK-valid group (n?=?110). The PPK parameter values for VPA were calculated in the PPK-model group by using the NONMEM software. Ultimately, a biological model and a final model were established. Each model was then used to independently predict the concentrations of the PPK-valid group to validate the two models.

Results

There was a significant effect of the CYP2C19 and CYP2C9 genotypes on the pharmacokinetic (PK) variability (P?<?0.01) in the final PPK model of CL/F. The interindividual CL was calculated according to the final model: CL/F?=?0.0951?×?(1?+?e0.0267?×?(3???genotype))?+?0.0071?×?age (L/h). The coefficient of variation (CV) (omega CL/F) of the final model was 29.3%, while that of the biological model was 31.7%. Based on the genotype, the individual PK parameters can be calculated more accurately than before.

Conclusion

The CYP2C19 and CYP2C9 genotypes significantly influenced the PK variability of VPA, as quantified by NONMEM software.
  相似文献   

7.
Toxic effects of copper on aquatic organisms in polluted water bodies have garnered particular attention in recent years. Microalgae play an important role in aquatic ecosystems, and they are sensitive to heavy metal pollution. Thus, it is important to clarify the mechanism of copper toxicity first for ecotoxicology studies. In this study, the physiological, biochemical and gene expression characteristics of a model green microalga, Chlamydomonas reinhardtii, with 0, 50, 150 and 250 μM copper treatments were investigated. The response of C. reinhardtii to copper stress was significantly shown at a dose dependent manner. Inhibition of cell growth and variation of total chlorophyll content were observed with copper treatments. The maximum photochemical efficiency of PSII, actual photochemical efficiency of PSII and photochemical quenching value decreased in the 250 μM copper treatment with minimum values equal to 28, 24 and 60 % of the control values respectively. The content of lipid peroxidation biomarker malondialdehyde with copper treatments increased with a maximum value sevenfold higher than the control value. Inhibition of cell growth and photosynthesis was ascribed to peroxidation of membrane lipids. The glutathione content and activities of antioxidant enzymes, glutathione S-transferase, glutathione peroxidase, superoxide dismutase and peroxidase were induced by copper. Interestingly, the expression of antioxidant genes and the photosynthetic gene decreased in most copper treatments. In conclusion, oxidative stress caused by production of excess reactive oxidative species might be the major mechanism of copper toxicity on C. reinhardtii.  相似文献   

8.
A biomonitoring study was conducted using some biotic (Pomadasys hasta and Lutjanus russellii fish) and abiotic (water and sediment) components of the Red Sea coast of Hodeida, Yemen Republic along two polluted sites (Al-Dawar beach and Urj village) in comparison to a reference site (Al-Nukhailah beach). The studied fish biomarkers included hepatosomatic index (HSI), condition factor (K), scaled mass index (SMI), catalase, glutathione-S-transferase (GST), malondialdehyde (MDA), total protein and albumin. In addition, metals (Fe, Cu, Zn, Pb and Cd) concentrations in water and sediment were measured and sediment pollution assessment was carried out using contamination factor (CF), geoaccumulation index (Igeo), pollution load index (PLI) and enrichment factor (EF). The studied metals concentration in water and sediment samples showed significant increase among the polluted sites in comparison to the reference site. Sediment pollution assessment generally confirmed that Urj village was the most contaminated site followed by Al-Dawar beach. Catalase, GST and MDA proved to be the most responsive biomarkers with increased values of GST and MDA at sites influenced by agricultural, urban and industrial activities while catalase, HSI, K, SMI, total protein and albumin showed the opposite trend. This study recommends monitoring of sediment Igeo and EF values as well as SMI, catalase, GST and MDA as sensitive indicators of different anthropogenic activities and their effects on aquatic ecosystems under complex and different gradients of metal pollution. In addition, P. hasta proved to be more sensitive towards the detected pollution condition.  相似文献   

9.
In order to investigate the effects of heavy metal stress on woody plant defense against phytophagous insects, we studied development and reproduction traits of the gypsy moth, Lymantria dispar that were separately fed with leaves plucked from poplar seedlings (Populus alba berolinensis) grown in either non-contaminated soil (control), Cd-contaminated soil (1.5?mg/kg), Zn-contaminated soil (500?mg/kg) or Pb-contaminated soil (500?mg/kg). The results showed that feeding on Cd or Pb stressed poplar leaves significantly decreased L. dispar larval weights, body lengths and head capsule widths, pupal weights and female fecundity, and delayed the duration of larval development. Similar effects from the Zn stressed poplar leaves were also observed on all the above mentioned variables except male pupal weight and larval development duration that showed no differences from the control. Cd, Zn, or Pb stressed poplar leaves had no significant effects on L. dispar larval survival, pupation and emergence rates; in fact, both larval survival and pupation rates reached 100%. These results suggest that Cd, Zn or Pb stress in P. alba berolinensis might help the trees defend against the defoliator, however; L. dispar may in turn have an effective detoxification mechanism for lessening the effects of plant-mediated defenses and heavy metals in leaves on larval survival, pupation and eclosion.  相似文献   

10.
The bacterial community associated with apparently healthy and diseased Hydra magnipapillata was investigated by pyrosequencing analysis of bacterial 16S rRNA. Proteobacteria and Bacteroidetes were the main phyla associated with the apparently healthy specimens. In diseased Hydra, Chlorobi, Cyanobacteria, Planctomycetes and Actinobacteria were also present in addition to Proteobacteria and Bacteroidetes. The diseased specimens were associated with greater abundance of Proteobacteria, Betaproteobacteria, Burkholderiales and Comamonadaceae. The major taxa contained potentially pathogenic bacteria that may influence health of H. magnipapillata. Species diversity and community composition significantly differed between healthy and diseased H. magnipapillata.  相似文献   

11.
Heavy metals can lead to osmotic stress by disrupting the regulation of sodium ion in aquatic organisms. In this study, gene expression patterns and enzymatic activities of Na+/K+-ATPase in the monogonont rotifer, Brachionus koreanus were measured after exposure to different Cd (7.5, 15, and 30 mg/L), and Pb (0.1, 0.5, and 1.0 mg/L), respectively. As results, a significant increase in Bk Na+/K+-ATPase activity was observed after exposure to Cd and Pb in a concentration-dependent manner. Bk Na +/K +-ATPase mRNA level was significantly upregulated in the Cd-exposed group, whereas its level was reduced in the Pb-exposed group. These findings indicate that heavy metals could induce osmotic stress in B. koreanus, and Na+/K+-ATPase may be involved in cellular ho-meostasis in response to heavy metal exposure. This study is helpful for the understanding of the molecular mode of action of B. koreanus in response to heavy metals.  相似文献   

12.
Zafirlukast, a cysteinyl leukotriene receptor antagonist, is indicated for the treatment of patients with mild to moderate asthma. Zafirlukast is metabolized mainly by CYP3A4 and CYP2C9. We investigated the effects of the major CYP2C9 variant alleles in Asian populations, CYP2C9*3 and CYP2C9*13, on the pharmacokinetics of zafirlukast in healthy Korean subjects. A single 20-mg oral dose of zafirlukast was given to 23 Korean male subjects divided into two genotype groups according to CYP2C9 genotypes, CYP2C9EM (n = 11; CYP2C9*1/*1) and CYP2C9IM (n = 12; 9 and 3 carriers of CYP2C9*1/*3 and *1/*13, respectively). Zafirlukast concentrations were determined using a validated HPLC–MS/MS analytical method in plasma samples collected after the drug intake. Compared with the CYP2C9EM group, the Cmax and AUCinf of zafirlukast in the CYP2C9IM group were 1.44- and 1.70-fold higher, respectively (p < 0.01 and p < 0.0001). The CL/F of zafirlukast was 42.8 % lower in the CYP2C9IM group compared with the CYP2C9EM group (p < 0.001). Slightly higher Cmax and AUC, and lower CL/F of zafirlukast were observed in subjects with the CYP2C9*1/*13 genotype compared with the CYP2C9*1/*3 genotype subjects. CYP2C9*3 and CYP2C9*13 alleles significantly affected the plasma concentrations of zafirlukast.  相似文献   

13.
Clomiphene citrate, a selective estrogen receptor modulator, is metabolized into its 4-hydroxylated active metabolites, primarily by CYP2D6. In this study, we investigated the effects of the most common CYP2D6 variant allele in Asians, CYP2D6*10, on the pharmacokinetics of clomiphene and its two active metabolites (4-OH-CLO and 4-OH-DE-CLO) in healthy Korean subjects. A single 50-mg oral dose of clomiphene citrate was given to 22 Korean subjects divided into three genotype groups according to CYP2D6 genotypes, CYP2D6*wt/*wt (n = 8; *wt = *1 or *2), CYP2D6*wt/*10 (n = 8) and CYP2D6*10/*10 (n = 6). Concentrations of clomiphene and its metabolites were determined using a validated HPLC–MS/MS analytical method in plasma samples collected up to 168 h after the drug intake. There was a significant difference only in the Cmax of clomiphene between three CYP2D6 genotype groups (p < 0.05). Paradoxically, the elimination half-life (t1/2) and AUC of both active metabolites were all significantly increased in the CYP2D6*10 homozygous carriers, compared with other genotype groups (all p < 0.001). The AUCinf of corrected clomiphene active moiety in CYP2D6*10/*10 subjects was 2.95- and 2.05-fold higher than that of CYP2D6*wt/*wt and *wt/*10 genotype groups, respectively (both p < 0.001). Along with the partial impacts on the biotransformation of clomiphene and its metabolites by CYP2D6 genetic polymorphism, further studies on the effects of other CYP enzymes in a multiple-dosing condition can provide more definite evidence for the inter-individual variabilities in clomiphene pharmacokinetics and/or drug response.  相似文献   

14.
Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, is used for the treatment of rheumatoid arthritis and osteoarthritis. The predominant hepatic metabolism of celecoxib to celecoxib carboxylic acid (CCA) is mediated mainly by CYP2C9. We investigated the effects of the major CYP2C9 genetic variants in Asian populations, CYP2C9*3 and CYP2C9*13, on the pharmacokinetics of celecoxib and its carboxylic acid metabolite in healthy Korean subjects. A single 200-mg oral dose of celecoxib was given to 52 Korean subjects with different CYP2C9 genotypes: CYP2C9EM (n = 26; CYP2C9*1/*1), CYP2C9IM (n = 24; CYP2C9*1/*3 and *1/*13), and CYP2C9PM (n = 2; CYP2C9*3/*3). Celecoxib and CCA concentrations in plasma samples collected up to 48 or 96 h after drug intake were determined by HPLC–MS/MS. The mean area under the plasma concentration–time curve (AUC0–∞) of celecoxib was increased 1.63-fold (P < 0.001), and the apparent oral clearance (CL/F) of celecoxib was decreased by 39.6% in the CYP2C9IM genotype group compared with that of CYP2C9EM (P < 0.001). The overall pharmacokinetic parameters for celecoxib in CYP2C9*1/*13 subjects were similar to those in CYP2C9*1/*3 subjects. Two subjects with CYP2C9PM genotype both showed markedly higher AUC0–∞, prolonged half-life, and lower CL/F for celecoxib than did subjects with CYP2C9EM and IM genotypes. CYP2C9*3 and CYP2C9*13 variant alleles significantly affected the plasma concentration of celecoxib.  相似文献   

15.
The concentrations of Pb, Cd and Zn were investigated in the blood of pigeons (Columba livia) in order to assess the degree of pollution by heavy metal. For this, wild city pigeons were caught at four different locations in Mohammedia classified according to their industrial activity and road traffic density. Significant difference in heavy metal concentrations were observed between sites studied, the highest lead and cadmium levels were found in industrial area and center town, while the highest zinc level was found in the less contaminated area. These results indicate that the industrial activities and the road traffic are the most important source of pollution.  相似文献   

16.
The seven-spot ladybird beetle, Coccinella septempunctata, is a major natural enemy of aphids in the field and in greenhouses in China and is part of integrated pest management (IPM). Imidacloprid, a highly efficient insecticide that not only kills aphids at lethal concentrations, but also can cause various sublethal effects in nontarget organisms. To strengthen IPM and its sustainability, it is important assessing possible side effects on natural enemies. When the effects of sublethal concentrations (LC5 and 10%LC5) of imidacloprid on C. septempunctata were evaluated, the adult longevity was shortened by 23.97 and 28.68?%, and the fecundity reduced by 52.81 and 56.09?% compared to control population. In the F1 generation (i.e., the progeny of the exposed individuals), the juvenile development was slower by 1.44 days and 0.66 days, and the oviposition period was shortened by 10 and 13 days, respectively. The fecundity of the F1 generation decreased by 17.88, 44.03 and 51.69?% when exposed to 1%LC5, 10%LC5, and LC5, respectively. The results of demographical growth estimates showed that the intrinsic rate of increase (r m ) and net reproductive rate (R 0 ) were lower in C. septempunctata populations that had been exposed to sublethal concentrations of imidacloprid. The results emphasize the importance of assessing side effects of low imidacloprid concentrations on such predator species, even at the transgenerational level.  相似文献   

17.
Aging is a key risk factor for many diseases, understanding the mechanism of which is becoming more important for drug development given the fast-growing aging population. In the course of our continued efforts to discover anti-aging natural products, the active constituent 6-shogaol was isolated from Zingiber officinale Roscoe. The chemical structure of 6-shogaol was identified by comparison of its NMR data with literature values. The lifespan-extending effect of 6-shogaol was observed in a dose-dependent manner in Caenorhabditis elegans that has been widely used as a model organism for human aging studies. Mechanism of such action was investigated using C. elegans models, suggesting that 6-shogaol is capable of increasing stress tolerances via enzyme induction. The proposed mechanism was further supported by observation of the increase in SOD and HSP expressions upon treatment with 6-shogaol in transgenic strains of C. elegans which contain GFP-based reporters. In addition, the mechanism was elaborated by confirming that the effect observed for 6-shogaol is independent from other aging-related factors that are known to affect the aging process of C. elegans.  相似文献   

18.
Bradysia odoriphaga Yang et Zhang is a destructive insect pest of Chinese chives. To understand the current status of insecticide resistance of B. odoriphaga in China, the sensitivity variation of eight field populations to six commonly used insecticides, including chlorpyrifos, phoxim, imidacloprid, thiamethoxam, clothianidin and beta-cypermethrin were evaluated. The results showed that almost all the tested B. odoriphaga populations had developed moderate to high resistance to chlorpyrifos and phoxim. There were different resistance levels found in the eight field populations among the three neonicotinoids, imidacloprid, thiamethoxam and clothianidin. Imidacloprid was very effective against B. odoriphaga in most tested populations except those from Yangzhou (10.35-fold) and Tangshan (14.56-fold). While four populations kept susceptible to thiamethoxam, the other four populations showed decreased susceptibility or low resistance. To clothianidin, five populations displayed moderate resistance, two populations displayed low resistance, and one population exhibited susceptibility, respectively. All the tested populations were resistance to beta-cypermethrin, the highest resistance was found in the Tangshan population with a resistance ratio of 172.56-fold. The results of this study provided valuable information for choosing insecticides for control and integrated resistance management of B. odoriphaga.  相似文献   

19.
20.
This study examines the spatial difference in genetic variation for tolerance to a pesticide, fenitrothion, in Daphnia galeata at field sites in Lake Kasumigaura, Japan. We estimated genetic values of isofemale lines established from dormant eggs of D. galeata collected from field sampling sites with the toxicant threshold model applied using acute toxicity. We compared genetic values and variances and broad-sense heritability across different sites in the lake. Results showed that the mean tolerance values to fenitrothion did not differ spatially. The variance in genetic value and heritability of fenitrothion tolerance significantly differed between sampling sites, revealing that long-term ecological risk of fenitrothion may differ between local populations in the lake. These results have implications for aquatic toxicology research, suggesting that differences in genetic variation of tolerance to a chemical among local populations must be considered for understanding the long-term ecological risks of the chemical over a large geographic area.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号