bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of in vitro biotransformation of propranolol with HPLC, MS/MS, and two bioassays
Authors: Nałęcz‐Jawecki Grzegorz , Wójcik Tomasz , Sawicki Józef 
Published: January 2008

AbstractThe majority of human drugs enter aquatic systems after ingestion and subsequent excretion in the form of parent compounds and metabolites. Environmental exposure to drug metabolites has not been reported so far. The goal of the present study was to apply the in vitro method of biotransformation of compounds with S9 fraction to the ecotoxicological analysis. β‐adrenoceptor antagonist propranolol was metabolized with S9 rat liver fraction. The parent compound was quantified with HPLC, and the metabolites were identified with QToF MS. Propranolol was metabolized rapidly, during the first hour its level decreased by 80 and 50% of the initial 20 and 100 mg L−1, respectively. Ten peaks were observed on the HPLC‐RF chromatogram. Four peaks were identified with QToF MS/MS propranolol (m/z = 260), N‐desisopropylpropranolol (m/z = 218), hydroxypropranolol (m/z = 276), and hydroxy N‐desisopropranolol glycol (m/z = 235). Then the ecotoxicity of the reaction mixture was studied with two bioassays Spirotox with the protozoan Spirostomum ambiguum and Thamnotoxkit F™ with the anostracean crustacean Thamnocephalus platyurus. Propranolol is twofolds more toxic to Spirotox than to Thamnotoxkit F with 24 h‐EC50 = 1.77 mg L−1 and 24 h‐LC50 = 3.86 mg L−1, respectively. No statistically significant differences were found between the toxicity of the reaction mixtures after S9 biotransformation and the propranolol solution. These results indicate that the biological activity of the metabolites is similar to that of the parent drug. The presented method of in vitro biotransformation of drugs with S9 fraction followed by HPLC and ecotoxicity tests, may be used as screening method for evaluation of the toxicity of drug metabolites. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.
An examination of the antibiotic effects of cylindrospermopsin on common gram‐positive and gram‐negative bacteria and the protozoan Naegleria lovaniensis
Authors: Rasmussen J. Paul , Cursaro Michael , Froscio Suzanne M. , Saint Christopher P. 
Published: January 2008

AbstractThe importance of the toxin cylindrospermopsin to the function and fitness of the cyanobacteria that produce it remains a matter of conjecture. Given that the structure of cylindrospermopsin has commonalities with other antibacterial protein synthesis inhibitors, such as streptomycin, authors tested the possibility that the toxin might act as an antibacterial compound that can kill competing microbes. Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa were tested by the minimal inhibitory concentration method and significant antibacterial activity was only observed at a cylindrospermopsin concentration of 300 μg mL−1 after exposure for 5 days. No effect on log phase growth of E. coli was observed for this same toxin concentration. Protein synthesis was inhibited by cylindrospermopsin in E. coli 70S extracts, reduced by 25% compared with controls when treated with 41.5 μg mL−1 of the toxin; however, a much greater reduction of 97% was observed for chloramphenicol in the same experiment. Naegleria lovaniensis, a phagotrophic protozoan, was more susceptible to cylindrospermopsin, with a decrease in the number of N. lovaniensis plaques after 24‐h treatment with 5–50 μg mL−1 of toxin and an LC50 of ∼60 μg mL−1. Given these results, cylindrospermopsin is clearly not antibacterial at concentrations found in environmental waters, nor will it adversely affect N. lovaniensis at these concentrations. For organisms that are able to ingest cylindrospermopsin‐producing cells, the response of N. lovaniensis to the toxin suggests that only a few ingested cells would be enough to kill predatory organisms with similar susceptibility. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.
Cell‐cycle protein modifications in the kidney of Mus spretus from Doñana National Park
Authors: Leoni Silvia , Torrice Alessia , Chiuchiarelli Giorgia , Bruscalupi Giovannella , Cristaldi Mauro 
Published: January 2008

AbstractOn April 1998 a tailing dam of the Aznalcollar pyrite mine partially collapsed and released to the Guadiamar river acidic water and mud containing toxic metals threatening the Doñana National Park, a Spanish wildlife reserve located near the estuary of Guadalquivir river. To assess the possible biological effects on terrestrial ecosystems, biochemical markers were assayed in the kidneys of Algerian mice (Mus spretus) collected in several areas of Doñana and Guadiamar river. Biomarkers assayed are proteins involved in cell cycle regulation, in particular cyclins and their associated kinases, and some cell cycle inhibitors. Moreover Mitogen Activated Protein Kinases (MAPK), a signal transduction system involved in cell division, p53, a protein involved in growth arrest after DNA damage, and HSP70, an early stress‐induced protein, were assayed. The kidneys of animals collected one year after the ecological disaster had increased levels of PCNA (proliferating cell nuclear antigen), indicating an increased number of cells in the S phase of cell cycle. This shift of cells from G0 to S phase is due to increased levels of cyclins D1, E, and A, to decreased levels of p21 and p27 cdk inhibitors, and to activation of MAPK cascade. On the other hand, p53 and HSP70 levels are not changed. These data demonstrate that the presence of toxic metals after ecological disaster provoked the induction of kidney cell proliferation interpretable as a compensatory cell growth after tissue damage and apoptosis, and that could lead to the genomic instability characteristic of cancer cell. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.
Geostatistical conditional simulation for the assessment of contaminated land by abandoned heavy metal mining
Authors: Ersoy Adem , Yunsel Tayfun Yusuf , Atici Ümit 
Published: January 2008

AbstractAbandoned mine workings can undoubtedly cause varying degrees of contamination of soil with heavy metals such as lead and zinc has occurred on a global scale. Exposure to these elements may cause to harm human health and environment. In the study, a total of 269 soil samples were collected at 1, 5, and 10 m regular grid intervals of 100 × 100 m area of Carsington Pasture in the UK. Cell declustering technique was applied to the data set due to no statistical representativity. Directional experimental semivariograms of the elements for the transformed data showed that both geometric and zonal anisotropy exists in the data. The most evident spatial dependence structure of the continuity for the directional experimental semivariogram, characterized by spherical and exponential models of Pb and Zn were obtained. This study reports the spatial distribution and uncertainty of Pb and Zn concentrations in soil at the study site using a probabilistic approach. The approach was based on geostatistical sequential Gaussian simulation (SGS), which is used to yield a series of conditional images characterized by equally probable spatial distributions of the heavy elements concentrations across the area. Postprocessing of many simulations allowed the mapping of contaminated and uncontaminated areas, and provided a model for the uncertainty in the spatial distribution of element concentrations. Maps of the simulated Pb and Zn concentrations revealed the extent and severity of contamination. SGS was validated by statistics, histogram, variogram reproduction, and simulation errors. The maps of the elements might be used in the remediation studies, help decision‐makers and others involved in the abandoned heavy metal mining site in the world. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.
Effects of the statin antihyperlipidemic agent simvastatin on grass shrimp, Palaemonetes pugio
Authors: Key Peter B. , Hoguet Jennifer , Reed Lou Ann , Chung Katy W. , Fulton Michael H. 
Published: January 2008

AbstractThis study investigated lethal effects (i.e., survival) and sublethal effects (glutathione, GSH; lipid peroxidation, LPx; cholesterol, CHL; and acetylcholinesterase, AChE) of the antihyperlipidemic drug simvastatin on larval and adult grass shrimp (Palaemonetes pugio). The 96‐h LC50 test for larvae resulted in an estimated LC50 of 1.18 mg/L (95% confidence interval 0.98–1.42 mg/L). The adult 96‐h LC50 was >10.0 mg/L. GSH and AChE levels for both the larvae and the adults were not significantly affected by simvastatin exposure. LPx levels in the larvae were significantly higher than controls in the lowest and the highest simvastatin exposures. In adult grass shrimp, LPx levels were highest in the three lowest simvastatin exposures. CHL levels were significantly reduced in larvae at the highest simvastatin exposure level of 1 mg/L while adult CHL was not affected. Both lethal and sublethal effects associated with simvastatin exposure were only observed at concentrations well above those reported in the environment. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.
Ym1 and Ym2 expression in a mouse model exposed to diesel exhaust particles
Authors: Song Hyun‐Mi , Jang An‐Soo , Ahn Mi‐Hyun , Takizawa Hajime , Lee Shin‐Hwa , Kwon Ji‐Hee , Lee Young‐Mok , Rhim TaiYoun , Park Choon‐Sik 
Published: January 2008

AbstractBackground: Chitinase may play a role in regulating allergic diseases. Objective: We studied the role of chitinase in a mouse model exposed to diesel exhaust particles (DEP). Mice were exposed to intranasal DEP (0.6 mg/mL) for 5 days and challenged with aerosolized DEP (6 mg/m3) on days 6–8. Enhanced pause (Penh), as an airway obstruction marker, was measured on day 9, and bronchoalveolar lavage (BAL) fluid and lung tissues were collected on day 10. The expression of Ym1 and Ym2 mRNA was assessed in lung tissue extracts by reverse transcription‐polymerase chain reaction. Results: DEP induced significant increases in methacholine‐induced Penh and IL‐4 levels in BAL fluid relative to the control group. Peribronchial and perivascular inflammatory cell infiltrates were prominent in the DEP group. DEP induced Ym1 and Ym2 mRNA expression in lung tissue extracts relative to the control group. Conclusion: These results demonstrate that DEP induced airway hyperresponsiveness and Ym mRNA expression via a Th2 cell‐biased response, suggesting that chitinase may play an important role in airway inflammation and responsiveness upon exposure to DEP in a mouse model, and may therefore be involved in regulating allergic diseases. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.
Combined repeated dose and reproductive/developmental toxicity screening test of the nitrophenolic herbicide dinoseb, 2‐sec‐butyl‐4,6‐dinitrophenol, in rats
Authors: Matsumoto Mariko , Furuhashi Tadakazu , Poncipe Carlo , Ema Makoto 
Published: January 2008

AbstractIn a combined repeated dose toxicity study with reproduction/developmental toxicity screening test, Crj:CD(SD)IGS rats were dosed with dinoseb, 2‐sec‐butyl‐4,6‐dinitrophenol, by gavage at 0 (vehicle), 0.78, 2.33, or 7.0 mg/kg bw/day. Six males per group were dosed for a total of 42 days beginning 14 days before mating. Twelve females per group were dosed for a total of 44–48 days beginning 14 days before mating to day 6 of lactation throughout the mating and gestation period. Recovery groups of six males per group and nonpregnant six females per group were dosed for 42 days followed by a 14‐day recovery period. No deaths were observed in males of any dose group or in females of the recovery groups. At 7.0 mg/kg bw/day, eight females died and two animals were moribund during late pregnancy, and a significant decrease in body weight gain was found in both sexes. Hematocrit was significantly higher at 0.78 mg/kg bw/day and above in the main group males at the end of administration period. Reduction in extramedullary hematopoiesis in the spleen was significant at 2.33 mg/kg bw/day in the main group females. Sperm analysis revealed a decrease in sperm motility and an increase in the rates of abnormal sperm, abnormal tail, and abnormal head at 7.0 mg/kg bw/day. A number of dams delivered their pups and of dams with live pups at delivery was significantly lowered in the 7.0 mg/kg bw/day group. Based on these findings, the LOAEL for males and NOAEL for females were 0.78 mg/kg bw/day, and the NOAEL for reproductive/developmental toxicity was considered to be 2.33 mg/kg bw/day. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.
Differences of Cu accumulation and Cu‐induced ATPase activity in roots of two populations of Elsholtzia haichowensis Sun
Authors: Ke Wenshan , Xiong Zhiting , Chen Shijian , Wang Zhenghe 
Published: January 2008

AbstractTwo populations of Elsholtzia haichowensis, which are from an uncontaminated site (Hong'an) and a Cu mine site (Tonglushan) in Hubei province, China, were studied for ATPase activities and Cu accumulation of roots under hydroponic conditions. The root tolerance indices were markedly higher in Tonglushan population than in Hong'an population under Cu stress conditions. The root Cu concentration in Tonglushan population was significantly lower than that in Hong'an population in all Cu treatments. The Cu‐stimulated ATPase activity increased significantly under 1 μM Cu, reached a peak at 5 μM Cu and then, began to decrease. However, no significant change of ATPase activity was observed in Hong'an population except for an obvious decrease in 80 μM Cu treatment. These results showed that Cu‐ATPase might exist in the root plasma membrane of Tonglushan population and play a possible role in resistance to copper. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.
Detoxification and antioxidant responses in diverse organs of Jenynsia multidentata experimentally exposed to 1,2‐ and 1,4‐dichlorobenzene
Authors: Monferran Magdalena V. , Pesce Silvia F. , Cazenave Jimena , Wunderlin Daniel A. 
Published: January 2008

AbstractWe report changes in activities of detoxification and antioxidant enzymes as well as lipid peroxidation levels in liver, gills, and brain of Jenynsia multidentata exposed to 1,2‐ and 1,4‐dichlorobenzene (DCB). Fish were captured at an unpolluted area, transported to the laboratory, and acclimated previous to experiments. Exposures were carried out using 1,2‐DCB at 0.5, 1, 5, and 10 mg L−1 and 1,4‐DCB at 0.05, 0.1, 1, and 5 mg L−1. After 24‐h exposure, fish were sacrificed and dissected separating liver, gills, and brain of each fish. Organs were used for enzyme extractions, evaluating antioxidant system through the assay of glutathione reductase, guaiacol peroxidase, glutathione peroxidase, catalase as well as detoxification system by measuring glutathione‐S‐transferase (GST) activity. Additionally, thiobarbituric acid reactive substances (TBARS) method was used to evaluate the peroxidation of lipids. No changes in GST activity were found in liver of fish exposed to DCBs but in gills and brain of exposed fish. The detoxification system was activated at lower concentrations of 1,2‐DCB than 1,4‐DCB. Antioxidant response is activated in liver at low DCB concentrations, followed by a drop at highest levels. We also found activation of the antioxidant system in gills and brain of exposed fish. On the other hand, we did not observe changes in TBARS concentrations in liver or gills of exposed fish with respect to controls, but in brain of fish exposed to 1,2‐DCB (≥0.5 mg L−1) and 1,4‐DCB (5 mg L−1). Responses of both detoxification and antioxidant systems of J. multidentata suggest that 1,2‐DCB is more toxic than 1,4‐DCB to this specie. To the extent of our knowledge, this is the first report of oxidative stress induced by DCBs in fish. Our results evidence that the brain is the organ most severely affected by the oxidative stress caused by DCBs. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.
Multigeneration assessment of nonylphenol and endosulfan using a model Australian freshwater fish, Melanotaenia fluviatilis
Authors: Holdway Douglas A. , Hefferman Jenelle , Smith Anna 
Published: January 2008

AbstractChanges over two generations in offspring and reproductive ability were recorded in crimson‐spotted rainbowfish (Melanotaenia fluviatilis), a model Australasian freshwater fish, following a 24 h exposure to nominal nonylphenol concentrations of 50, 100, 500, 1000, 2250, and 5000 μg/L and following a 4 h exposure to nominal endosulfan concentrations of 1.0, 5.0, 10, 22, 33, and 50 μg/L. There were also four replicated control treatments: control 1 and 2 and solvent control 1 and 2, as well as “positive” female and male controls: 1 μg/L estradiol 1 and 2 and 1 μg/L testosterone 1 and 2. Results suggested that there may be some parental transfer of toxicants to embryos even over this short exposure period. Fertility of M. fluviatilis was reduced by a 24 h pulse exposure of adults to 100 μg/L nonylphenol and a 4 h exposure to 1.0 μg/L endosulfan. Hatch rates were significantly reduced after exposure to nonylphenol, endosulfan, and estradiol control but not in solvent controls and testosterone control. Significant correlations were found between reproductive and physiological parameters for nonylphenol and endosulfan exposed F0 adult rainbowfish. The major reproductive effects were on hatchability of the F1 generation and the gonadosomatic indices of male F1. The respective nominal NOEC and LOEC's for nonylphenol were 50 and 100 μg/L, and for endosulfan were <1.0 and 1 μg/L. These observed effects have the potential to significantly impact exposed rainbowfish populations through the observed ∼45% reduction of hatchability and thus larval production. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.
Bioaccumulation and oxidative stress in submerged macrophyte Ceratophyllum demersum L. upon exposure to pyrene
Authors: Yin Ying , Wang Xiaorong , Sun Yuanyuan , Guo Hongyan , Yin Daqiang 
Published: January 2008

AbstractLaboratory experiments were carried out to investigate pyrene bioaccumulation and its consequent biological responses in submerged macrophyte Ceratophyllum demersum. Plants were exposed to different levels (0.01, 0.02, 0.05, 0.07, 0.1 mg/L) of pyrene for 10 days, and the pyrene content, and total free radicals in plant were analyzed. The pyrene concentration in plant was highly correlated to exposure concentration (R2 = 0.990). Electron paramagnetic resonance (EPR) analysis revealed that pyrene exposure significantly increased total free radicals in the plants. A strong positive correlation (R2 = 0.956) between O generation and pyrene contents implied that pyrene exposure induced reactive oxygen species (ROS) and led to oxidative stress in C. demersum. The activities of antioxidant enzymes and the contents of glutathione were determined. Change in the contents of malondialdehyde (MDA) was also studied. Results indicated that the bioaccumulation of pyrene resulted in the changes of the antioxidant defense system and the production of ROS with the oxidative stress, ultimately induced damnification in C. demersum. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.
Effect of irrigation with lake water containing microcystins on microcystin content and growth of ryegrass, clover, rape, and lettuce
Authors: Crush J. R. , Briggs L. R. , Sprosen J. M. , Nichols S. N. 
Published: January 2008

AbstractThe effect of irrigation with lake water containing a variety of microcystins on accumulation of toxins, or toxin metabolites, and plant growth in ryegrass, clover, rape, and lettuce, was investigated in a glasshouse experiment. The plants were grown in sand culture and received either three or six applications of lake water, which was applied either directly to the sand surface or to the plant shoots. As determined by LC–MS, each plant received 170 μg of a mixture of 10 different microcystins per application. Microcystins in plant samples were extracted with 70% methanol and analyzed by Adda‐specific ELISA. For the shoot application treatment, microcystins were not present at measurable levels in shoots of ryegrass or rape, but were present in lettuce [0.79 mg/kg dry weight (DW)] and clover (0.20 mg/kg DW). Total microcystin concentration in roots did not vary greatly depending on whether treatment water was applied directly to the sand, or reached the roots via run‐off from the shoots. Microcystins in roots were highest in clover (1.45 mg/kg DW), intermediate in lettuce (0.68 mg/kg DW) and low in ryegrass (0.20 mg/kg DW), and rape (0.12 mg/kg DW). There was no evidence for root‐to‐shoot translocation of microcystins. Three applications of microcystins reduced shoot DW of ryegrass, rape and lettuce, and increased root DW of ryegrass and lettuce. Clover DW was not changed by treatment with microcystins. The results show that irrigation with water containing microcystins has the potential to move microcystins into farm animal and human food chains at concentrations that can exceed recommended tolerable limits. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.
Toxic effects of carbendazim and n‐butyl isocyanate, metabolites of the fungicide benomyl, on early development in the African clawed frog, Xenopus laevis
Authors: Yoon Chun‐Sik , Jin Jung‐Hyo , Park Joo‐Hung , Yeo Chang‐Yeol , Kim Song‐Ja , Hwang Yong‐Gi , Hong Sung‐Jin , Cheong Seon‐Woo 
Published: January 2008

AbstractWe investigated the toxic effects of carbendazim and n‐butyl isocyanate (BIC), metabolites of the fungicide benomyl, on development in the African clawed frog, Xenopus laevis. To test the toxic effects, frog embryo teratogenesis assays using Xenopus were performed. Embryos were exposed to various concentrations of carbendazim (0–7 μM) and BIC (0–0.2 μM). LC100 for carbendazim and BIC were 7 and 0.2 μM, respectively, and the corresponding LC50, determined by probit analysis, were 5.606 and 0.135 μM. Exposure to carbendazim concentrations ≥3 μM and BIC concentrations ≥0.1 μM resulted in 10 different types of severe external malformation. Histological examinations revealed dysplasia of the brain, eyes, intestine, and somatic muscle, and swelling of the pronephric ducts. These phenomena were common in both test groups. The tissue‐specific toxic effects were investigated with an animal cap assay. Neural tissues are normally induced at a high frequency by activin A, however, the induction of neural tissues was strongly inhibited by the addition of carbendazim. Conversely, the addition of BIC resulted in weak inhibition of neural tissues. Electron micrographs of animal cap explants revealed degeneration of cell junctions in the carbendazim‐treated group, but not in the BIC‐treated group. Numerous residual yolk platelets and mitochondrial degeneration were commonly observed in both test groups. The gene expression of cultivated animal cap explants was investigated by reverse transcriptase‐polymerase chain reaction and revealed that expression of the neural‐specific marker neural cell adhesion molecule was more strongly inhibited in the carbendazim‐treated group than in the BIC‐treated group. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.