Toxicity of silver nanoparticles and ionic silver: Comparison of adverse effects and potential toxicity mechanisms in the freshwater clam Sphaerium corneum

Abstract

A range of studies has addressed possible environmental impacts of nanosilver, but most focused on acute effects in few species. Moreover, it remains unclear if toxic effects are particle-specific or mediated by released silver ions. We investigated chronic effects of nanosilver and soluble silver (AgNO₃) on the freshwater bivalve Sphaerium corneum. Animals were exposed to nanosilver (0–500?μg?Ag?L^?1) and AgNO₃ (0–318?μg?Ag?L^?1) over 28 days, and effects on reproduction and behavioral changes were assessed. To explore toxic mechanisms, we evaluated the effects on intracellular levels of reactive oxygen species (ROS) and the activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase). We further explored the activity of the sodium–potassium adenosine triphosphatase (Na⁺/K⁺-ATPase). Chronic exposure to nanosilver and AgNO₃ resulted in negative effects on reproduction at concentrations of 5 and 3.18?µg?Ag?L^?1 (LOEC), respectively. ROS levels significantly increased after exposure to nanosilver at 10?µg?Ag?L^?1 and AgNO₃ at 63.5?µg?Ag?L^?1. Both forms of silver altered the activities of antioxidant enzymes. Nanosilver (500?μg?Ag?L^?1) and AgNO₃ (318?μg?Ag?L^?1) inhibited Na⁺/K⁺-ATPase activity by 82.6 and 78.9%, respectively. Nanoparticulate and soluble silver produced similar effects in S. corneum suggesting that toxicity of nanosilver is mainly mediated by dissolution of nanoparticles in the test media or after uptake by the test organisms.     

Protective effects of Scutellaria lindbergii root extract against oxidative-induced cell and DNA damage in mouse fibroblast-like cells

Context: Scutellaria lindbergii Rech. f. (Lamiaceae) is an Iranian species of Scutellaria which has been shown to exert antimicrobial, antioxidant and cytotoxic effects. Objective: The protective properties of total methanol extract (TME) of S. lindbergii and its fractions (defatted and CH₂Cl₂) were investigated against cytotoxic and genotoxic effects of H₂O₂ in NIH 3T3 cell line as non-malignant cells. Materials and methods: The cells were incubated with different concentrations of S. lindbergii root extracts [TME (15–250?μg ml^?1), defatted fraction (15–500?μg ml^?1) and CH₂Cl₂ fraction (5–40?μg ml^?1)] and toxic concentration of H₂O₂ (200?µM) at 37?°C for 2?h concurrently and Cell viability was quantitated by MTT assay. The antigenotoxic effect of extracts was investigated using comet assay. The cells were incubated with extracts [TME (25–250?μg ml^?1), defatted fraction (25–500?μg ml^?1) and CH₂Cl₂ fraction (5–40?μg ml^?1)] and H₂O₂ (25?µM) at 4?°C for 20?min, then the comet assay was performed. DNA damage was expressed as percentage tail DNA. Results: Total methanol extract of S. lindbergii and its fractions had a significant inhibitory effect on DNA damage. The IC₅₀ values of TME, defatted fraction and CH₂Cl₂ fraction against DNA damage were determined as 48, 138 and 8?μg ml^?1, respectively. Conclusion: S. lindbergii extracts can prevent oxidative DNA damage, which is likely due to its flavonoids and phenolic compounds as antioxidant constituents.     

Simultaneous determination of sparfloxacin and commonly used H2 receptor antagonists by RP-HPLC: application to in vitro drug interactions

Innovative, simple, economical, and rapid reverse phase HPLC method has been developed and validated for simultaneous determination of sparfloxacin (SPFX) and cimetidine, ranitidine, and famotidine (H₂ receptor antagonists) in bulk material, pharmaceutical formulations, and human serum. Chromatographic system was consisting of schemed HPLC system having UV detector set at 232?nm for cimetidine and, 250?nm for famotidine and ranitidine. Purospher STAR C₁₈ (250?×?4.6?mm, 5?μm) column was used, and the mobile phase (methanol, water and ACN 54:41:5 v/v/v pH 2.7 adjusted by phosphoric acid) was delivered at a flow rate of 1.0?ml?min^?1. The proposed method is specific, accurate (98.02–102.136%), precise (intra-day and inter-day variation 0.501–2.179%) and linear (R ²?>?0.999) with in the desired range 0.3125–25?μg?ml^?1 concentration. The detection limit and quantification limit were 0.009–0.084 and 0.030–0.255?μg?ml^?1, respectively. Paired t test was applied to verify the results. The anticipated method is applicable to routine analysis of SPFX and H₂ receptor antagonists in pharmaceutical formulations as well as in human serum samples. The proposed method is also applied to study interaction studies of SPFX with H₂ receptor antagonists.     

Quantitative biokinetics of titanium dioxide nanoparticles after oral application in rats: Part 2

The biokinetics of a size-selected fraction (70?nm median size) of commercially available and ⁴⁸V-radiolabeled [⁴⁸V]TiO₂ nanoparticles has been investigated in female Wistar-Kyoto rats at retention timepoints 1?h, 4?h, 24?h and 7 days after oral application of a single dose of an aqueous [⁴⁸V]TiO₂-nanoparticle suspension by intra-esophageal instillation. A completely balanced quantitative body clearance and biokinetics in all organs and tissues was obtained by applying typical [⁴⁸V]TiO₂-nanoparticle doses in the range of 30–80?μg?kg^?1 bodyweight, making use of the high sensitivity of the radiotracer technique. The [⁴⁸V]TiO₂-nanoparticle content was corrected for nanoparticles in the residual blood retained in organs and tissue after exsanguination and for ⁴⁸V-ions not bound to TiO₂-nanoparticles. Beyond predominant fecal excretion about 0.6% of the administered dose passed the gastro-intestinal-barrier after one hour and about 0.05% were still distributed in the body after 7 days, with quantifiable [⁴⁸V]TiO₂-nanoparticle organ concentrations present in liver (0.09?ng?g^?1), lungs (0.10?ng?g^?1), kidneys (0.29?ng?g^?1), brain (0.36?ng?g^?1), spleen (0.45?ng?g^?1), uterus (0.55?ng?g^?1) and skeleton (0.98?ng?g^?1). Since chronic, oral uptake of TiO₂ particles (including a nano-fraction) by consumers has continuously increased in the past decades, the possibility of chronic accumulation of such biopersistent nanoparticles in secondary organs and the skeleton raises questions about the responsiveness of their defense capacities, and whether these could be leading to adverse health effects in the population at large. After normalizing the fractions of retained [⁴⁸V]TiO₂-nanoparticles to the fraction that passed the gastro-intestinal-barrier and reached systemic circulation, the biokinetics was compared to the biokinetics determined after IV-injection (Part 1). Since the biokinetics patterns differ largely, IV-injection is not an adequate surrogate for assessing the biokinetics after oral exposure to TiO₂ nanoparticles.     

Assessing triclosan-induced ecological and trans-generational effects in natural phytoplankton communities: a trait-based field method

We exposed replicated phytoplankton communities confined in semi-permeable membrane-based mesocosms to 0, 0.1, 1 and 10 μg L^?1 triclosan (TCS) and placed them back in their original environment to investigate the occurrence of trans-generational responses at individual, population and community levels. TCS diffused out of mesocosms with a half-life of less than 8 h, so that only the parental generation was directly stressed. At the beginning of the experiment and after 7 days (approximately 2 generations) we analysed responses in the phytoplankton using scanning flow-cytometry. We acquired information on several individually expressed phenotypic traits, such as size, biovolume, pigment fluorescence and packaging, for thousands of individuals per replicated population and derived population and community aggregated traits. We found significant changes in community functioning (increased productivity in terms of biovolume and total fluorescence), with maximal effects at 1 μg L^?1 TCS. We detected significant and dose-dependent responses on population traits, such as changes in abundance for several populations, increased average size and fluorescence of cells, and strong changes in within-population trait mean and variance (suggesting micro-evolutionary effects). We applied the Price equation approach to partition community effects (changes in biovolume or fluorescence) in their physiological and ecological components, and quantified the residual component (including also evolutionary responses). Our results suggested that evolutionary or inheritable phenotypic plasticity responses may represent a significant component of the total observed change following exposure and over relatively small temporal scales.     

Effects of the fungicide metiram in outdoor freshwater microcosms: responses of invertebrates, primary producers and microbes

The ecological impact of the dithiocarbamate fungicide metiram was studied in outdoor freshwater microcosms, consisting of 14 enclosures placed in an experimental ditch. The microcosms were treated three times (interval 7 days) with the formulated product BAS 222 28F (Polyram^®). Intended metiram concentrations in the overlying water were 0, 4, 12, 36, 108 and 324 μg a.i./L. Responses of zooplankton, macroinvertebrates, phytoplankton, macrophytes, microbes and community metabolism endpoints were investigated. Dissipation half-life (DT₅₀) of metiram was approximately 1–6 h in the water column of the microcosm test system and the metabolites formed were not persistent. Multivariate analysis indicated treatment-related effects on the zooplankton (NOEC_community = 36 μg a.i./L). Consistent treatment-related effects on the phytoplankton and macroinvertebrate communities and on the sediment microbial community could not be demonstrated or were minor. There was no evidence that metiram affected the biomass, abundance or functioning of aquatic hyphomycetes on decomposing alder leaves. The most sensitive populations in the microcosms comprised representatives of Rotifera with a NOEC of 12 μg a.i./L on isolated sampling days and a NOEC of 36 μg a.i./L on consecutive samplings. At the highest treatment-level populations of Copepoda (zooplankton) and the blue-green alga Anabaena (phytoplankton) also showed a short-term decline on consecutive sampling days (NOEC = 108 μg a.i./L). Indirect effects in the form of short-term increases in the abundance of a few macroinvertebrate and several phytoplankton taxa were also observed. The overall community and population level no-observed-effect concentration (NOEC_microcosm) was 12–36 μg a.i./L. At higher treatment levels, including the test systems that received the highest dose, ecological recovery of affected measurement endpoints was fast (effect period < 8 weeks).     

New evidences of Roundup® (glyphosate formulation) impact on the periphyton community and the water quality of freshwater ecosystems

Argentina is the second largest world producer of soybeans (after the USA) and along with the increase in planted surface and production in the country, glyphosate consumption has grown in the same way. We investigated the effects of Roundup^® (glyphosate formulation) on the periphyton colonization. The experiment was carried out over 42 days in ten outdoor mesocosms of different typology: “clear” waters with aquatic macrophytes and/or metaphyton and “turbid” waters with great occurrence of phytoplankton or suspended inorganic matter. The herbicide was added at 8 mg L^?1 of the active ingredient (glyphosate) in five mesocosms while five were left as controls (without Roundup^® addition). The estimate of the dissipation rate (k) of glyphosate showed a half-life value of 4.2 days. Total phosphorus significantly increased in treated mesocosms due to Roundup^® degradation what favored eutrophication process. Roundup^® produced a clear delay in periphytic colonization in treated mesocosms and values of the periphytic mass variables (dry weight, ash-free dry weight and chlorophyll a) were always higher in control mesocosms. Despite the mortality of algae, mainly diatoms, cyanobacteria was favored in treated mesocosms. It was observed that glyphosate produced a long term shift in the typology of mesocosms, “clear” turning to “turbid”, which is consistent with the regional trend in shallow lakes in the Pampa plain of Argentina. Based on our findings it is clear that agricultural practices that involve the use of herbicides such as Roundup^® affect non-target organisms and the water quality, modifying the structure and functionality of freshwater ecosystems.     

Ecotoxicological effects of bisphenol A and nonylphenol on the freshwater cladocerans Ceriodaphnia silvestrii and Daphnia similis

Toxicities of bisphenol A (BPA) and nonylphenol (NP) to the neotropical freshwater cladocerans Ceriodaphnia silvestrii and Daphnia similis were studied under laboratory conditions. Acute exposures to BPA generated mean 48-h EC₅₀ values of 14.44 (6.02–22.85) mg L^?1 for C. silvestrii and 12.05 (1.73–22.37) mg L^?1 for D. similis. When the organisms were exposed to acute doses of NP, mean 48-h EC₅₀ values were 0.055 (0.047–0.064) mg L^?1 (C. silvestrii) and 0.133 (0.067–0.200) mg L^?1 (D. similis). Ceriodaphnia silvestrii was also tested in chronic bioassays, which resulted in mean 8-d IC₂₅ values of 2.43 (2.16–2.69) mg L^?1 BPA [no observed effect concentration (NOEC): 1.38?mg L^?1] and 0.020 (0.015–0.026) mg L^?1 NP (NOEC: 0.015?mg L^?1). These laboratory tests are valuable to broaden the understanding of the environmental threat posed by BPA and NP in aquatic ecosystems, and to increase the knowledge about the sensitivity of neotropical indigenous species to these contaminants. In addition to the laboratory bioassays, species sensitivity distributions were used to suggest protective concentrations of BPA and NP to prevent adverse effects on freshwater organisms. According to the obtained results, concentrations lower than 36.47?µg L^?1 BPA and 1.39?µg L^?1 NP are not expected to adversely impact aquatic organisms in natural ecosystems.     

Dietary (periphyton) and aqueous Zn bioaccumulation dynamics in the mayfly Centroptilum triangulifer

Diet is often the predominant route of trace metal exposure in aquatic insects. In freshwater ecosystems, periphyton serves as a primary source of food to many aquatic insects and is a major sink for trace metals. We investigated the bioconcentration of the essential metal Zn by periphyton using ⁶⁵Zn as a radiotracer. At relatively low dissolved concentrations (2–20?μg?L^?1), non steady state Zn bioconcentration by periphyton averaged 6,099?±?2,430-fold, with much of the variability determined by loading regime (number of renewals and duration of exposures). Labeled periphyton was used as a food source for dietary accumulation studies with the mayfly Centroptilum triangulifer. After 29?days, larvae concentrated Zn 19-, 16- and 17-fold relative to dietary Zn concentrations of 8.1, 43.2 and 82.3?μg?g^?1 (dry weight), respectively. Adults from that same cohort only concentrated Zn 8-, 3- and 3- fold relative to those same dietary concentrations, revealing that mayflies lose significant Zn prior to reaching adulthood. Anecdotal evidence suggests that this loss occurs prior to emergence to the subimago, as negligible Zn was found in the subimago to imago exuvium. Across a range of adult tissue concentrations, maternal transfer consistently averaged 26.7?%. Uptake (k_u, 0.26?L?g^?1?d^?1) and efflux rate constants (k_e, 0.001–0.007?d^?1) were measured and assimilation efficiencies from dietary Zn concentrations of 4.9 and 59.7?μg Zn?g^?1 were estimated to be 88?±?4?% and 64?±?15?%, respectively. Both life cycle and biodynamic modeling approaches point towards diet being the primary route of Zn bioaccumulation in this mayfly.     

Toxicity of TiO2 nanoparticles on soil nitrification at environmentally relevant concentrations: Lack of classical dose–response relationships

Titanium-dioxide nanoparticles (TiO₂-NPs) are increasingly released in agricultural soils through, e.g. biosolids, irrigation or nanoagrochemicals. Soils are submitted to a wide range of concentrations of TiO₂-NPs depending on the type of exposure. However, most studies have assessed the effects of unrealistically high concentrations, and the dose–response relationships are not well characterized for soil microbial communities. Here, using soil microcosms, we assessed the impact of TiO₂-NPs at concentrations ranging from 0.05 to 500?mg kg^?1?dry-soil, on the activity and abundance of ammonia-oxidizing archaea (AOA) and bacteria (AOB), and nitrite-oxidizing bacteria (Nitrobacter and Nitrospira). In addition, aggregation and oxidative potential of TiO₂-NPs were measured in the spiking suspensions, as they can be important drivers of TiO₂-NPs toxicity. After 90?days of exposure, non-classical dose–response relationships were observed for nitrifier abundance or activity, making threshold concentrations impossible to compute. Indeed, AOA abundance was reduced by 40% by TiO₂-NPs whatever the concentration, while Nitrospira was never affected. Moreover, AOB and Nitrobacter abundances were decreased mainly at intermediate concentrations nitrification was reduced by 25% at the lowest (0.05?mg?kg^?1) and the highest (100 and 500?mg?kg^?1) TiO₂-NPs concentrations. Path analyses indicated that TiO₂-NPs affected nitrification through an effect on the specific activity of nitrifiers, in addition to indirect effects on nitrifier abundances. Altogether these results point out the need to include very low concentrations of NPs in soil toxicological studies, and the lack of relevance of classical dose–response tests and ecotoxicological dose metrics (EC50, IC50…) for TiO₂-NPs impact on soil microorganisms.     

Cr and Hg toxicity assessed in situ using the structural and functional characteristics of algal communities

The toxicity of mercury and chromium on algal community structure have been assessed using in situ N₂ase activity, pigment diversity, autotrophic index, and ¹⁴C uptake of algae. The location was in the river Ganga and controlled ecosystem pollution experiment enclosures were used. Maximum inhibition of algal number was observed at 0.8 μg Hg mL^?1 followed by 8.0 μg Cr mL^?1. Unicellular forms, except for Anorthoneis excentrica, were very sensitive to test metals used. The decline in algal number was concentration dependent and metal specific at generic and species levels. Complete elimination of three and six species was observed respectively at 8.0 μg Cr mL^?1 and 0.8 μg Hg mL^?1 after 12 days' exposure. Likewise, a concentration-dependent and metal-specific increase in autotrophic index and pigment diversity of phytoplankton was recorded for Hg and Cr. Inhibition of ¹⁴C uptake of phytoplankton in Ganga water was almost equal (79%) at 0.8 μg Hg mL^?1 and 8.0 μg Cr mL^?1 (78%). Although complete inhibition of in situ N₂ase was observed at 0.8 μg Hg mL^?1, it was only 80% with 8.0 μg Cr mL^?1. Our study suggests that heavy metals inhibit both structural and functional variables of phytoplankton in field microcosms. Hence this technique seems to hold potential for the biomonitoring of heavy metal toxicity in the field.     

Antifungal efficiency of miconazole and econazole and the interaction with transport protein: A comparative study

Abstract

Context: Miconazole (MIZ) and econazole (ECZ) are clinically used as antifungal drugs.

Objective: The drug effect and binding property with transport protein human serum albumin of MIZ and ECZ were studied.

Materials and methods: The antifungal efficiency was investigated by microdiluting drug solutions from 0 to 48?μmol?L^?1 through microcalorimetry and voltammetry studies. Transmission electron microscopy was used for morphological observations of C. albicans. The interaction with HSA was studied by electrochemical methods, fluorescence spectrometry, electron microscopy, and molecular simulation.

Results: IC₅₀ of MIZ and ECZ for C. albicans were obtained as 19.72 and 29.90?μmol?L^?1. Binding constants of MIZ and ECZ with HSA of 2.36?×?10⁴ L?mol^?1 and 3.73?×?10⁴ L?mol^?1 were obtained. After adding MIZ solution of 12 and 40?μmol?L^?1, the peak currents increased to 4.887 and 6.024?μA. The peak currents of C. albicans in the presence of 20 and 48?μmol?L^?1 ECZ were 4.701 and 5.544?μA. The docking scores for MIZ and ECZ of the best binding conformation in site I and site II were 5.60, 4.79, 5.63, and 5.85.

Discussion and conclusion: Strong inhibition to the metabolism of C. albicans and destructive effect was proved for both drugs. The lower IC₅₀, growth rate constant of C. albicans, and higher peak current, reveal stronger antifungal activity of MIZ. Both drugs show an efficient quenching effect to intrinsic fluorescence residues of protein. MIZ mainly binds on site I while ECZ on site II. Molecular modeling experiments give further insight of the binding mechanism.     

Application of in-situ bioassays with macrophytes in aquatic mesocosm studies

Aquatic mesocosm studies assess ecotoxicological effects of chemicals by using small artificial ponds as models of lentic ecosystems. In this study, methods of controlled insertion of macrophytes within an outdoor mesocosm study were explored. Although analytically confirmed concentrations of the model herbicide terbuthylazine were high enough to expect direct effects on phytoplankton, functional parameters and dominant taxa abundance indicated only minor and transient effects. In-situ assays with Lemna minor, Myriophyllum spicatum, Potamogeton lucens and Chara globularis revealed adverse effects at concentrations in accordance with literature data. Complex interactions such as nutrient limitation and competition were possible reasons for the observed growth promotion at the lower concentration of about 5 μg/l terbuthylazine. The approach of macrophyte in-situ bioassays within a mesocosm study proved to be applicable. Presumed advantages are simultaneous acquisition of toxicity data for several species of aquatic plants under more realistic conditions compared to laboratory tests and inclusion of macrophytes as important structural and functional components in mesocosms while limiting their domination of the model ecosystem.     

Simultaneous determination of glipizide and glimepride by Rp-Hplc in dosage formulations and in human serum

In this article, simple, liquid chromatographic method has been developed and validated for the determination of glipizide and glimepride in pharmaceutical formulations and in human serum. Chromatographic separation was carried out on a Nucleosil, C₁₈ (10?μm, 25?×?0.46?cm) column using the mobile phase 80:20 methanol:water with pH adjusted to 3.5 at a flow rate 1?ml?min^?1. Peak intensity of the drugs was recorded at 230?nm with UV detection. The linearity of the method was studied over the concentration range of 0.15–5?μg?ml^?1 (r?=?0.9979) and 0.5–7.5?μg?ml^?1 (r?=?0.9988) for glipizide and glimepride, respectively. Detection and quantitation limits were found to be 20 and 46?ng?ml^?1 and 70 and 141?ng?ml^?1 for glipizide and glimepride, respectively. There was no significant interference of extra pharmacopeial ingredients and serum observed in the assay of these two drugs.     

Industrial worker exposure to airborne particles during the packing of pigment and nanoscale titanium dioxide

Context: Titanium dioxide (TiO2) factory workers’ source specific exposure and dose to airborne particles was studied extensively for particles between 5?nm and 10 μm in size.

Objective: We defined TiO₂ industry workers’ quantitative inhalation exposure levels during the packing of pigment TiO₂ (pTiO₂) and nanoscale TiO₂ (nTiO₂) material from concentrations measured at work area.

Methods: Particle emissions from different work events were identified by linking work activity with the measured number size distributions and mass concentrations of particles. A lung deposit model was used to calculate regional inhalation dose rates in units of particles min^?1 and μg min^?1 without use of respirators.

Results: Workers’ average exposure varied from 225 to 700 μg m^?3 and from 1.15?×?10⁴ to 20.1?×?10⁴ cm^?4. Over 90% of the particles were smaller than 100?nm. These were mainly soot and particles formed from process chemicals. Mass concentration originated primarily from the packing of pTiO₂ and nTiO₂ agglomerates. The nTiO₂ exposure resulted in a calculated dose rate of 3.6?×?10⁶ min^?1 and 32 μg min^?1 where 70% of the particles and 85% of the mass was deposited in head airways.

Conclusions: The recommended TiO₂ exposure limits in mass by NIOSH and in particle number by IFA were not exceeded. We recommend source-specific exposure assessment in order to evaluate the workers’ risks. In nTiO₂ packing, mass concentration best describes the workers’ exposure to nTiO₂ agglomerates. Minute dose rates enable the simulation of workers’ risks in different exposure scenarios.     

Effect of piperine on CYP2E1 enzyme activity of chlorzoxazone in healthy volunteers

1.?The purpose of the present study was to investigate the effect of piperine (PIP) on CYP2E1 enzyme activity and pharmacokinetics of chlorzoxazone (CHZ) in healthy volunteers.

2.?An open-label, two period, sequential study was conducted in 12 healthy volunteers. A single dose of PIP 20?mg was administered daily for 10 days during treatment phase. A single dose of CHZ 250?mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected at predetermined time intervals after CHZ dosing and analyzed by HPLC.

3.?Treatment with PIP significantly enhanced maximum plasma concentration (C_max) (3.14–4.96?μg/mL)_, area under the curve (AUC) (10.46–17.78?μg h/mL), half life (T_1/2) (1.26–1.82?h) and significantly decreased elimination rate constant (K_el) (0.57–0.41?h?^??¹), apparent oral clearance (CL/F) (24.76–13.65?L/h) of CHZ when compared to control. In addition, treatment with PIP significantly decreased C_max (0.22–0.15?μg/mL), AUC (0.94–0.68?μg h/mL), T_1/2 (2.54–1.68?h) and significantly increased K_el (0.32–0.43?h?^??¹) of 6-hydroxychlorzoxazone (6-OHCHZ) as compared to control. Furthermore, treatment with PIP significantly decreased metabolite to parent (6-OHCHZ/CHZ) ratios of C_max, AUC, T_1/2 and significantly increased K_el ratio of 6-OHCHZ/CHZ, which indicate the decreased formation of CHZ to 6-OHCHZ.

4.?The results suggest that altered pharmacokinetics of CHZ might be attributed to PIP mediated inhibition of CYP2E1 enzyme, which indicate significant pharmacokinetic interaction present between PIP and CHZ. The inhibition of CYP2E1 by PIP may represent a novel therapeutic benefit for minimizing ethanol induced CYP2E1 enzyme activity and results in reduced hepatotoxicity of ethanol.     

Optimization and validation of RP-HPLC method for simultaneous estimation of palbociclib and letrozole

A simple, rapid, and robust RP-HPLC method have been developed and validated to measure palbociclib (PB) and letrozole (LT) at single wavelength (254?nm). A isocratic elution of samples performed on Intersil C₈ (4.6?mm?×?250?mm particle size 5?μm) column with mobile phase consisting 0.02 M sodium dihydrogen phosphate buffer (pH 5.5): acetonitrile: methanol (80:10:10 v/v/v) delivered at flow rate 1.0?mL?min^?1. A good linear response was achieved over the range of 5–50?μg?mL^?1. The LODs for PB and LT were found to be 0.098 and 0.0821 µg?mL^?1, while the LOQs for PB and LT were 0.381–0.315 µg?mL^?1, respectively. The method was quantitatively evaluated in terms of system suitability test, linearity, precision, accuracy (recovery) and robustness as per standard guidelines. The method is simple, convenient and suitable for the analysis of PB and LT in bulk drug.     

A comparison of the fate and effects of two pyrethroid insecticides (lambda-cyhalothrin and cypermethrin) in pond mesocosms

The fate and effects of two pyrethroid insecticides (lambda-cyhalothrin and cypermethrin) were investigated in replicated 25 m³ pond mesocosms. Three pesticide treatments which simulated spray drift deposition were examined: 0.7 g a.i. ha^-1 cypermethrin and 0.17 and 1.7 g a.i. ha^-1 lambda-cyhalothrin. Based on the use rate and pesticidal activity of the chemicals, the cypermethrin and lower lambda-cyhalothrin rates were approximately equivalent. After applications, pyrethroid residues in the water column declined rapidly. Treatment-related effects were observed on some macroinvertebrate taxa, most notably the Asellidae and Gammaridae. Surfacedwelling insects also suffered initial knock-down, particularly in the 1.7 g a.i. ha^-1 lambda-cyhalothrin treatment, but there was recovery after the spray period. No adverse effects occurred on algae, macrophytes or zooplankton, but there were occasional enhancements (e.g. algal biomass and abundances of copepod nauplii and Rotifera) which may have been indirect effects. An overall comparison of the treatments indicated that the higher lambda-cyhalothrin rate had the greatest effects, whilst the cypermethrin application had a somewhat greater impact than the lower lambda-cyhalothrin treatment rate (due to effects on peracarid crustaceans). The study indicated that should spray drift occur at the levels expected for either pyrethroid's normal use patterns, potential impacts on natural aquatic ecosystems would be minor and transient.     

The effects of endoplasmic reticulum stress inducer thapsigargin on the toxicity of ZnO or TiO2 nanoparticles to human endothelial cells

It was recently shown that ZnO nanoparticles (NPs) could induce endoplasmic reticulum (ER) stress in human umbilical vein endothelial cells (HUVECs). If ER stress is associated the toxicity of ZnO NPs, the presence of ER stress inducer thapsigargin (TG) should alter the response of HUVECs to ZnO NP exposure. In this study, we addressed this issue by assessing cytotoxicity, oxidative stress and inflammatory responses in ZnO NP exposed HUVECs with or without the presence of TG. Moreover, TiO₂ NPs were used to compare the effects. Exposure to 32?μg/mL ZnO NPs (p?2 NPs (p?>?0.05), significantly induced cytotoxicity as assessed by WST-1 and neutral red uptake assay, as well as intracellular ROS. ZnO NPs dose-dependently increased the accumulation of intracellular Zn ions, and ZnSO₄ induced similar cytotoxic effects as ZnO NPs, which indicated a role of Zn ions. The release of inflammatory proteins tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) or the adhesion of THP-1 monocytes to HUVECs was not significantly affected by ZnO or TiO₂ NP exposure (p?>?0.05). The presence of 250?nM TG significantly induced cytotoxicity, release of IL-6 and THP-1 monocyte adhesion (p?p?>?0.05). ANOVA analysis indicated no interaction between exposure to ZnO NPs and the presence of TG on almost all the endpoints (p?>?0.05) except neutral red uptake assay (p?相似文献   

Sensitivity of planktonic photosynthesis to various toxicants in the river rhine

Natural populations of phytoplankton from the lower River Rhine were exposed to selected pollutants in order to estimate their sensitivity to chemical pollution. The photosynthesis, measured as ¹⁴C incorporation, was inhibited by 50% when circa 100 μg · L^?1 copper or atrazine was added. Potassium dichromate (K₂Cr₂O₇) and an anionic detergent (tetrapropylbenzenesulphonate) affected the photosynthesis of Rhine phytoplankton only at concentrations of about 3 and 40 mg L^?1, respectively. A tenfold concentrate of the organic compounds from river water, harvested on XAD resin, inhibited the photosynthesis by 50%. Comparison of the results of this study with literature data indicate that the algal populations in the River Rhine are as sensitive and not more tolerant than several algae from less polluted habitats. These observations on the Rhine plankton also indicate that the pollution level in the River Rhine is likely to affect the photosynthesis of phytoplankton. This supports the request for a further reduction in toxicant input in the River Rhine. © 1993 John Wiley & Sons, Inc.