Induction of hepatic drug metabolizing enzymes in mammals by pesticides: A review

Abstract

The induction of drug metabolizing enzymes in mammals is summarized including both enzymes of the cytochrome P‐450‐dependent microsomal mixed function oxidase system and glutathione S‐transferases. Particular emphasis is placed on the role of pesticides as inducers, the early work being summarized while investigations carried out at North Carolina State University are considered in greater detail. Finally, the possible significance of induction is considered.     

Enclave development and ‘offshore corporate social responsibility’: Implications for oil-rich sub-Saharan Africa

This paper critically reflects on the challenges of engaging, proactively, in Corporate Social Responsibility (CSR) in oil-rich sub-Saharan Africa. Most of the region's oil production takes place in enclave-type environments offshore and in countries ruled by autocratic governments which generally exert minimal pressure on companies to embrace CSR. With companies having little sense of who to target in their local economic development policies and programs, there is always a possibility of ‘offshore CSR’ – recognized here as potentially-effective ideas for improving social welfare that linger within the enclave and never fully materialize – surfacing. The aim is to conceptualize and broaden understanding of the challenge of developing CSR programs in these settings, where there are no clear linkages to communities or local economies more generally.     

Interference with xenobiotic metabolic activity by the commonly used vehicle solvents dimethylsulfoxide and methanol in zebrafish (Danio rerio) larvae but not Daphnia magna

Organic solvents, such as dimethylsulfoxide (DMSO) and methanol are widely used as vehicles to solubilise lipophilic test compounds in toxicity testing. However, the effects of such solvents upon innate detoxification processes in aquatic organisms are poorly understood. This study assessed the effect of solvent exposure upon cytochrome P450 (CYP)-mediated xenobiotic metabolism in Daphnia magna and zebrafish larvae (4 d post fertilisation). Adult D. magna were demonstrated to have a low, but detectable, metabolism of ethoxyresorufin in vivo and this activity was not modulated by pre-exposure to DMSO or methanol (24 h, up to 0.1% and 0.05% v/v, respectively). In contrast, the metabolism of ethoxyresorufin in zebrafish larvae was significantly reduced by both solvents (0.1% and 0.05% v/v, respectively) after 24 h of exposure. In zebrafish, these observed decreases in activity towards ethoxyresorufin were accompanied by decreased expression of a variety of genes coding for drug metabolising enzymes (corresponding to CYP1, CYP2, CYP3 and UDP-glucuronyl transferase [UGT] family enzymes), measured by quantitative PCR. Reduction of gene expression and CYP1 enzyme activities by methanol (0.05% v/v) in zebrafish larvae was partially reversed by co-exposure with Aroclor 1254 (100 μg L⁻¹). Overall this study suggests that relatively low concentrations of organic solvents can impact upon the biotransformation of certain xenobiotics in zebrafish larvae, and that this warrants consideration when assessing compounds for metabolism and toxicity in this species.     

Diflubenzuron residue and persistence on an oak forest after aerial application

Abstract

A twenty hectare forest block in central Pennsylvania was aerially sprayed with diflubenzuron (Dimilin 25W®) at the dose of 33.23g A.I./ha in 9.4 litres/ha. Leaf samples were collected from the upper and lower canopies of 27 oaks and understory within this block on the day of spray, May 29, 1991. Canopy leaves were also collected on May 31, June 10, July 29 and September 26, 1991.

Recovery of diflubenzuron residues on fortified canopy‐leaf and litter‐leaf samples using analytical techniques employed in this study averaged 87.4% (SE = 7.5%) and 66.2% (SE = 8.2%), respectively.

On the day of spray, diflubenzuron residues on the upper canopy, lower canopy and understory averaged 81.18, 39.65 and 8.35 ng/cm², respectively. Diflubenzuron residues on canopy‐leaf samples collected 2, 12, 61 and 120 days post‐spray averaged 14.83 (SE = 10.19), 16.75 (SE = 9.95), 12.84 (SE = 8.25) and 11.20 (SE = 7.52) ng/cm², respectively. Diflubenzuron residues on litter‐leaf samples collected after leaf senescence ‐ 169 and 323 days post spray contained measurable amounts of diflubenzuron in 51 and 59% of the samples, respectively. Of the samples with measurable amounts of diflubenzuron, residues averaged 1.36 (SE = 2.44) and 0.65 ng/cm² (SE = 0.73) respectively.     

Effects of Soil Amendments at a Heavy Loading Rate Associated with Cover Crops as Green Manures on the Leaching of Nutrients and Heavy Metals from a Calcareous Soil

The potential risk of groundwater contamination by the excessive leaching of N, P and heavy metals from soils amended at heavy loading rates of biosolids, coal ash, N‐viro soil (1:1 mixture of coal ash and biosolids), yard waste compost and co‐compost (3:7 mixture of biosolids to yard wastes), and by soil incorporation of green manures of sunn hemp (Crotalaria juncea) and sorghum sudangrass (Sorghum bicolor × S. bicolor var. sudanense) was studied by collecting and analyzing leachates from pots of Krome very gravelly loam soil subjected to these treatments. The control consisted of Krome soil without any amendment. The loading rate was 205 g pot^? 1 for each amendment (equivalent to 50 t ha^? 1 of the dry weight), and the amounts of the cover crops incorporated into the soil in the pot were those that had been grown in it. A subtropical vegetable crop, okra (Abelmoschus esculentus L.), was grown after the soil amendments or cover crops had been incorporated into the soil. The results showed that the concentration of NO₃‐N in leachate from biosolids was significantly higher than in leachate from other treatments. The levels of heavy metals found in the leachates from all amended soils were so low, as to suggest these amendments may be used without risk of leaching dangerous amounts of these toxic elements. Nevertheless the level of heavy metals in leachate from coal ash amended soil was substantially greater than in leachates from the other treatments. The leguminous cover crop, sunn hemp, returned into the soil, increased the leachate NO₃‐N and inorganic P concentration significantly compared with the non‐legume, sorghum sudangrass. The results suggest that at heavy loading rates of soil amendments, leaching of NO₃ ^? could be a significant concern by application of biosolids. Leaching of inorganic P can be increased significantly by both co‐compost and biosolids, but decreased by coal ash and N‐viro soil by virtue of improved adsorption. The leguminous cover crop, sunn hemp, when incorporated into the soil, can cause the concentration of NO₃‐N to increase by about 7 fold, and that of inorganic P by about 23% over the non‐legume. Regarding the metals, biosolids, N‐viro soil and coal ash significantly increased Ca and Mg concentrations in leachates. Copper concentration in leachate was increased by application of biosolids, while Fe concentration in leachates was increased by biosolids, coal ash and co‐compost. The concentrations of Zn, Mo and Co in leachate were increased by application of coal ash. The concentrations of heavy metals in leachates were very low and unlikely to be harmful, although they were increased significantly by coal ash application.     

Nonparametric functional data estimation applied to ozone data: prediction and extreme value analysis

The study of extreme values and prediction of ozone data is an important topic of research when dealing with environmental problems. Classical extreme value theory is usually used in air-pollution studies. It consists in fitting a parametric generalised extreme value (GEV) distribution to a data set of extreme values, and using the estimated distribution to compute return levels and other quantities of interest. Here, we propose to estimate these values using nonparametric functional data methods. Functional data analysis is a relatively new statistical methodology that generally deals with data consisting of curves or multi-dimensional variables. In this paper, we use this technique, jointly with nonparametric curve estimation, to provide alternatives to the usual parametric statistical tools. The nonparametric estimators are applied to real samples of maximum ozone values obtained from several monitoring stations belonging to the Automatic Urban and Rural Network (AURN) in the UK. The results show that nonparametric estimators work satisfactorily, outperforming the behaviour of classical parametric estimators. Functional data analysis is also used to predict stratospheric ozone concentrations. We show an application, using the data set of mean monthly ozone concentrations in Arosa, Switzerland, and the results are compared with those obtained by classical time series (ARIMA) analysis.     

不同氮磷比对多年生水生植物生长特性影响的研究

从氮、磷等植物生长的环境因子出发,研究了高低氮磷营养水平下,不同氮／磷比例的富营养化水体对聚草（Myriophyllum spicatum）、黄花水龙（Jussiaea stipulacea Ohwi）、喜旱莲子草（Alternanthera philoxeroides）生长特性的影响。结果表明,聚草在氮磷比2：1时生物量最大,且生物量在高浓度水平处理明显大于低浓度水平处理（P〈0．01）;黄花水龙在氮磷比10：1～20：1时生物量最大,高低浓度水平处理问生物量无显著性差异;喜旱莲子草在较高氮磷比20：l～40：1时生物量最大,高浓度水平处理时生物量显著性高于低浓度水平处理（P〈0．05）。在低浓度水平处理时,氮为黄花水龙和喜旱莲子草生长的主要限制因子,磷为聚草生长的主要限制因子,且喜早莲子草叶绿素增长期较其他处理提前,而黄花水龙的叶绿素变化在高低营养水平下差异不显著。营养盐水平对聚草茎长和生物量的影响较对黄花水龙和喜旱莲子草的影响明显。     

Effects of deltamethrin on hepatic microsomal cytochrome p450‐dependent monooxygenases in carp

Abstract The in vivo effects of sublethal concentrations of deltamethrin (DM), a pyrethroid insecticide, on the hepatic microsomal cytochrome P450 (Cyt P450) content and the Cyt P450‐dependent monooxygenase activities (para‐nitrophenetole‐O‐deethylase, pNPOD; aminopyrene‐N‐demethylase, APND; ethylmorphine‐N‐demethylase, EMND; 7‐ethoxycoumarin‐O‐deethylase, ECOD; and ethoxyresorufin‐O‐deethylase, EROD) were examined in adult carp (Cyprinus carpió L.).

0.2 μg/1 DM treatment resulted in significant increases in APND, EMND and ECOD activities, whereas 2 μg/1 DM resulted in significant inhibitions of all studied isoenzyme activities with the exceptions of pNPOD and APND after 72 h. EROD was the only enzyme for which a slight increase in activity was observed. On repeated treatment, Cyt P450 could not be detected after 48 h, but the Cyt P420 level increased. All tested isoenzyme activities were inhibited, with the exception ofthat of EROD, which was enhanced.

All these changes in enzyme activities and Cyt P450 content demonstrate the effects of DM on fish. DM treatment at low concentration is presumed to cause induction of the Cyt P450‐dependent monooxygenases which may lead to faster metabolization of the insecticide. In contrast, DM at higher concentration strongly inhibited the activities of the studied enzymes. This finding may be due to the damaging effect of DM on the xenobiotic metabolizing enzyme systems offish.     

Genotoxicity of chromium in vitro on yeast: Interaction with DNA†

The genotoxicity of chromium chloride was investigated in cells of D₇ strain of Saccharomyces cerevisiae harvested either from logarithmic or stationary growth phase.

A weak induction of mifotic gene conversion and point reverse mutation was obtained when the incubations were performed using phosphate buffer. No genetic effect was observed when the incubations were performed using Tris‐HCl buffer.

The experiments with ⁵¹Cr radiotracer demonstrated that Cr³⁺ ion enters the yeast cells and binds to DNA even if the incubation mixture was performed with Tris HCl buffer. This behaviour could be due to the highest concentration of CrCl₃ that cause some damages to cytoplasmatic membrane.