Gemfibrozil Research Articles

Theoretical studies into the degradation mechanisms and kinetics of gemfibrozil mediated by hydroxyl and sulfate radicals in the aqueous phase and ecotoxicity evaluation

Gemfibrozil (GEM), an acidic pharmaceutical used to reduce plasma triglycerides and total cholesterol levels, persists in conventional wastewater treatment processes. However, understanding its degradation mechanism and kinetics through advanced oxidation processes (AOPs) remains unexplored. Therefore, this study employed density functional theory (DFT) at the M06-2X/6-311++G(3df,2p) //M06-2X/6-311G(d,p) level to theoretically investigate the oxidation of GEM by hydroxyl and sulfate radicals in aqueous environments. Mechanistic pathways, reaction kinetics, and ecotoxicological assessments were conducted. Two distinct mechanisms involving addition and hydrogen abstraction were delineated. The overall rate constants, accounting for diffusion-limited effects, were determined as 1.84 × 109 M−1 s−1 and 7.73 × 109 M−1 s−1 at 298 K for •OH and SO4•−-initiated reactions, respectively. Analysis revealed that hydrogen abstraction at the carboxyl group predominated, while favorable addition occurred at the carbon atom positioned at the 3rd position of the benzene ring. The calculated half-life of GEM initiated by •OH and SO4•− was approximately 377 and 90 s with their concentration of 10−12 mol/L at 298 K. Ecotoxicity assessment via quantitative structure-activity relationship (QSAR) indicated a certain degree of danger posed by GEM and its degradation by-products to aquatic organisms, albeit exhibiting lower toxicity compared to GEM itself.

Rapid Electrochemical Investigation of Gemfibrozil Using NiONPs/Multiwalled Carbon Nanotube Modified Carbon Paste Electrode: Analysis of Human Urine Sample and Antimicrobial Activity

AbstractIn this study, nickel oxide nanoparticles (NiONPs) were produced by the co‐precipitation method and characterized by scanning electron microscopy, X‐ray diffraction (XRD), Fourier transform‐infrared and Ultraviolet‐visible spectroscopy. XRD analysis showed an average crystal size of 6 nm, while SEM analysis exemplified the oblong form with a particle size of 12 nm. As‐prepared NiONPs were combined with multiwalled carbon nanotubes (MWCNTs) and graphite powder to prepare NiONPs‐MWCNTs modified carbon paste electrode (MCPE). The fabricated NiONPs‐MWCNTsMCPE sensor was used to analyze Gemfibrozil (GEM) in pharmaceutical formulations. Electrochemical methods such as cyclic voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy employed in sensor characterization and electroanalysis of GEM. The sensor exhibited excellent electrochemical behavior towards GEM. It showed a lower limit of detection (LOD, 2.7×10−8 M), the limit of quantification (LOQ, 9.07×10−8 M), higher sensitivity, higher linear range, and long‐term stability compared to the reported methods. The NiONPs‐MWCNTsMCPE sensor was evaluated for practical application by performing spiking tests in pharmaceutical formulations and human urine samples, demonstrating significant recovery, high effectiveness, and accuracy. Further, nanoparticles manifested promising antibacterial action against Staphylococcus aureus, E. coli, Klebsiella aerogenes, Pseudomonas aeruginosa, and Klebsiella aerogenes.

Lipid-Lowering Drug Gemfibrozil Protects Mice from Tay-Sachs Disease via Peroxisome Proliferator-Activated Receptor α.

Tay-Sachs disease (TSD) is a progressive heritable neurodegenerative disorder characterized by the deficiency of the lysosomal β-hexosaminidase enzyme (Hex-/-) and the storage of GM2 ganglioside, as well as other related glycoconjugates. Along with motor difficulties, TSD patients also manifest a gradual loss of skills and behavioral problems, followed by early death. Unfortunately, there is no cure for TSD; however, research on treatments and therapeutic approaches is ongoing. This study underlines the importance of gemfibrozil (GFB), an FDA-approved lipid-lowering drug, in inhibiting the disease process in a transgenic mouse model of Tay-Sachs. Oral administration of GFB significantly suppressed glial activation and inflammation, while also reducing the accumulation of GM2 gangliosides/glycoconjugates in the motor cortex of Tay-Sachs mice. Furthermore, oral GFB improved behavioral performance and increased the life expectancy of Tay-Sachs mice. While investigating the mechanism, we found that oral administration of GFB increased the level of peroxisome proliferator-activated receptor α (PPARα) in the brain of Tay-Sachs mice, and that GFB remained unable to reduce glycoconjugates and improve behavior and survival in Tay-Sachs mice lacking PPARα. Our results indicate a beneficial function of GFB that employs a PPARα-dependent mechanism to halt the progression of TSD and increase longevity in Tay-Sachs mice.

Detection of synthetic lipid‐lowering adulterants in herbal products using high‐performance thin‐layer chromatography

AbstractAdulterating herbal medicine with undeclared synthetic drugs is a worldwide problem that seriously threatens human health. To detect such illicit and not labeled synthetic hypolipidemic substances in herbal medicines, an analytical method to simultaneously identify and quantify atorvastatin (ATV) calcium, simvastatin (SIM), gemfibrozil (GEM), fenofibrate (FEN) belonging to two different classes of drugs (statins and fibrates) was developed based on high‐performance thin‐layer chromatography. The method consisted of Silica Gel G60 F254 precoated aluminum plate as stationary phase and toluene: ethyl acetate: formic acid (7:3:0.3, v/v/v) as optimized mobile phase. The densitometric evaluation wavelength was optimized at 254 nm. The Rf values of ATV, SIM, GEM, and FEN were 0.157, 0.268, 0.691, and 0.852, respectively. The linearity range is between 100–1500 ng/band for ATV and FEN and 200–3000 ng/band for SIM and GEM, respectively. The accuracy was found to be in the range of 97%–105%. The relative standard deviation of precision and robustness was found to be < 5%. However, the five screened market samples did not show the presence of adulteration of the above drugs. This method for the simultaneous determination of four drugs may be successfully employed to screen synthetic hypolipidemics as adulterants in herbal products and dietary supplements.

Effects of a chronic exposure to gemfibrozil in Carassius auratus

Lipid regulators, such as fibrates, are pharmaceuticals manufactured to treat dyslipidaemias in humans. Their constant use and discard combined to their environmental persistence and poor removal rates from wastewater makes of these emergent contaminants ubiquitous in aquatic systems, with gemfibrozil (GEM) being the most commonly detected fibrate in water. The present study aimed to describe the effects of a 28day waterborne exposure to both an environmentally relevant concentration (1.5 µg/L) and a spiked concentration (15 mg/L) of GEM, in adult individuals of the model organism Carassius auratus (goldfish). To this end, bioaccumulation of this compound in liver and muscle, as well as variations on haematological parameters, plasma biochemistry endpoints, and the expression of relevant target genes in the liver were investigated. The results indicated that, following exposure to the highest concentration of GEM, this compound accumulated in both liver and muscle. Similarly, significant increases were observed in haemoglobin levels, and mean corpuscular haemoglobin concentrations in individuals exposed to 15 mg/L of GEM. The biochemical profiling of plasma revealed significant decreases of cortisol and glucose levels, as well as a significant increase in the total antioxidant capacity (TAC) together with significant upregulations of gene transcripts related to antioxidant defences (gpx, gst) and lipid metabolism (apoa1). However, no changes were observed between treatments in the relative expression of key pro-inflammatory markers (il1β, il6 and il8) nor genetic markers of lipid metabolism (pparα pparβ and pparγ) or plasma levels of cholesterol and triglycerides. Overall, the results suggest that bioaccumulation of GEM in C. auratus triggers mild antioxidant responses at high doses but not at environmentally relevant ones.

Biodegradation of emerging organic pollutant gemfibrozil: Mechanism, kinetics and pathway modelling

The increasing population has raised the demand for pharmaceutical and personal care products to maintain a good health. Gemfibrozil (GEM), is extensively used as a lipid regulator and is frequently detected in wastewater treatment systems and poses deleterious health and ecological effects. Hence, the current study employing Bacillus sp. N2 reports the degradation of gemfibrozil via co-metabolism in 15 days. The study reported 86 % degradation with GEM (20 mgL-1) using sucrose (150 mgL-1) as a co-substrate; as compared to 42 % without a co-substrate. Further, time-profiling studies of metabolites revealed significant demethylation and decarboxylation reactions during degradation that leads to formation of six (M1, M2, M3, M4, M5, M6) metabolites as by-products. Based on the LC-MS analysis a potential degradation pathway for GEM by Bacillus sp. N2 was proposed. The degradation of GEM has not been reported so far and the study envisages eco-friendly approach to tackle pharmaceutical- active- compounds.

Gemfibrozil palliates adriamycin-induced testicular injury in male rats via modulating oxidative, endocrine and inflammatory changes in rats

Adriamycin (ADR), an antineoplastic drug, is widely used to treat different types of cancers. Yet, the usage is limited because of its severe side effects on testis. On the other hand, gemfibrozil (GEM), as an anti-hyperlipidemic drug, has other pharmacological effects independent of lipid- lowering activity including anti-inflammatory and antioxidant properties. The present experiment was designed to investigate the effect of GEM on ADR-induced testicular injury in male rats. A total of 28 male Wistar rats were divided into 4 equal groups: Control; ADR; ADR + GEM; GEM. Serum level of testosterone, luteinizing hormone and follicle stimulating hormone were assessed. Also, testicular tissue oxidant/antioxidant markers (malondialdehyde, total antioxidant capacity, nitric oxide, superoxide dismutase, catalase, glutathione peroxidase and glutathione) and proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) were measured. Histopathological studies were conducted on testes. GEM improved hormonal profile and antioxidant defenses in comparison with ADR-treated animals. GEM, significantly reduced the production of proinflammatory cytokines compared with ADR-treated animals. Hormonal and biochemical results were further supported by testicular histopathological findings. Thus, GEM might represent a promising therapeutic modality for the attenuation of testicular injury induced by ADR in clinic.

Prediction of pharmaceuticals removal in activated sludge system under different operational parameters using an extended ASM-PhACs model

Removal of pharmaceuticals is essential in wastewater treatment systems due to their release and accumulation in the environment, which are raising issues for the environment and human health. A mathematical model could be used to predict pharmaceuticals removal under various operational parameters and assess the contributions of different removal pathways to pharmaceuticals removal. Here an ASM-PhACs model was established to describe pharmaceuticals removal including diclofenac (DCF), erythromycin (ERY), gemfibrozil (GEM) and carbamazepine (CBZ) removal in activated sludge system. The pharmaceuticals removal processes linked to co-metabolic biodegradation through the growth of ammonia oxidizing bacteria (AOB), metabolic biodegradation through AOB, metabolic biodegradation through heterotrophic bacteria (HB) and sludge adsorption were incorporated into activated sludge model (ASM1) framework. The kinetic equations were established for each pharmaceuticals removal process. To provide the experimental data for model calibration and validation, two sets of batch tests were designed and conducted in the laboratory scale using SBR technology. According to the batch test data and results of sensitivity analysis, the newly added parameters and some original default parameters affecting pharmaceuticals removal processes were screened and calibrated. The model could accurately simulate all the dynamics of chemical oxygen demand, nitrogen and pharmaceuticals under various conditions. To explore the effect of operational parameters on pharmaceuticals removal efficiency, the wide range of operational parameters was analyzed during model simulation. According to the simulation results, both influent NH4+-N concentration and DO were found to be the significant parameters that impact the removal of DCF, ERY and GEM. AOB biodegradation played an important role in DCF, ERY and GEM removal. The developed model framework helps to investigate the removal mechanisms and key influencing factors of pharmaceuticals removal, thus providing guidelines for reactor design, operation and optimization aiming at pharmaceuticals removal.

Gemfibrozil, a lipid-lowering drug, improves hepatorenal damages in a mouse model of aging.

Gemfibrozil (GFZ) is a medication of the fibrate category with agonistic effects on peroxisome proliferator-activated receptor-α (PPAR-α) and is effective for hypertriglyceridemia and mixed dyslipidemia. This agent also has anti-inflammatory and antioxidant properties. The current study investigated the effects of GFZ on hepatorenal damages in a D-galactose (D-gal)-induced aging model. We used 28 male mice, which were equally and randomly divided into four groups as follows: normal, D-gal (150 mg/kg/day; intraperitoneal [i.p.], for 6weeks), GFZ (100 mg/kg/day GFZ, orally [p.o.]for 6 weeks), and the combined D-gal + GFZ. Liver and kidney function indices were measured as serum creatinine, blood urine nitrogen, alanine aminotransferase, and aspartate aminotransferase. Oxidative stress in hepatic and renal tissue was evaluated through malondialdehyde, superoxide dismutase, and glutathione peroxidase levels. Finally, the liver and kidney tissues were assessed for histopathological lesions. The results showed that D-gal-induced aging leads to abnormalities in liver and kidney function indices. D-gal also induced significant oxidative stress and histopathological lesions in these organs. GFZ improved function indices and oxidative stress compared to the D-gal-treated animals. Histological evaluations of the liver and kidney also confirmed these results. These data provide evidence for the potential therapeutic of GFZ in clinical practice for mitigating the hepatorenal damages of aging.

A Comprehensive Study of Gemfibrozil Complexation with β-Cyclodextrins in Aqueous Solution Using Different Analytical Techniques

Gemfibrozil (GEM) is a hypolipidemic agent, which is effective in reducing serum cholesterol and triglyceride levels. Complexation of GEM with native β-cyclodextrin (β-CD) and with the derivatives hydroxypropyl-β- and randomly methylated β-CD (HPβ-CD and Meβ-CD) was studied in aqueous solution of pH 2.8 and 7.0. The stability constants were determined by spectrofluorimetry, 1H-NMR spectroscopy and solubility assays. Considering the well-known difficulties to obtain similar stability constants by different techniques, the agreement of the values obtained supports the reliability of the results presented. The advantages and drawbacks of each analytical technique for the study of inclusion complexation were discussed as well. In addition, the thermodynamic parameters of complexation, enthalpy (ΔH) and entropy (ΔS), were determined and related to the type of molecular interactions that take place between GEM and the different cyclodextrins. Finally, solid dispersions were prepared by co-evaporation, kneading, vacuum desiccation, and coprecipitation, and complexation was evaluated by X-ray diffraction.

Contamination Characteristics and Ecological Risk Assessment of Pharmaceuticals and Personal Care Products (PPCPs) in the Third Drain of Ningxia

To investigate the contamination characteristics and potential ecological risks of pharmaceuticals and personal care products (PPCPs) in the Third Drain of Ningxia, 14 PPCPs were detected and analyzed using solid-phase extraction coupled with ultra-high performance liquid chromatography-tandem mass spectrometry. The results showed that these 14 PPCPs were detected in the Third Drain and its confluent streams, with total concentrations of 117.74-1947.64 ng·L-1 and 63.94-4509.39 ng·L-1, respectively. Detection ratios of gemfibrozil (GEM), caffeine (CAF), avobenzone (BM-DBM), benzophenone-3 (BP-3), 3-(4-methylbenzylidene)-camphor (4-MBC), and diethyltoluamide (DEET) were 100% in the drain. The highest-concentration pharmaceutical was GEM (7.78-721.84 ng·L-1), followed by CAF (41.74-246.86 ng·L-1), and the highest-concentration personal care product was DEET (3.17-219.91 ng·L-1), followed by BP-3 (56.92-150.14 ng·L-1). Concentrations of PPCPs at different sampling points exhibited spatial differences. The total PPCPs concentration increased dramatically and reached a maximum value after flowing through Pingluo County, then showed a decreasing trend downstream. Correlation analysis showed that 4-MBC was significantly positively correlated with COD (P<0.01). IBU, XMTD, TCC, and TCS were significantly correlated with NH4+-N (P<0.05). DIC, BF, CBZ, and DEET were significantly correlated with TN (P<0.05). The results indicated that concentrations of PPCPs were closely related to water quality indexes. Risk assessment showed that DIC, IBU, GEM, CBZ, CAF, and BP-3 had high risks, whereas BM-DBM, TCC, and TCS had moderate risks.

Metabolic Activation of Gemfibrozil Mediated by Cytochrome P450 Enzymes and Sulfotransferases.

Gemfibrozil (GEM), a lipid regulator, is a fibric acid derivative widely used in the treatment of hyperlipidemia. It has been reported that GEM can induce acute liver injury in the course of therapy in clinical practice, so it is necessary to elucidate the mechanisms of toxic action. The present study focused on metabolic activation of GEM, possibly participating in GEM-mediated liver injury. A benzylic alcohol metabolite (M1), along with a phenol metabolite (M2), was detected in microsomal incubations, rat primary hepatocyte culturing, and rats given GEM. A GSH conjugate (M3) was detected in cultured rat hepatocytes after exposure to GEM. Formation of M1 was found to be NADPH dependent, and generation of M3 required M1 and 3'-phosphoadenosine-5'-phosphosulfate. It is most likely that GEM was biotransformed to M1, which was further metabolized to a sulfate. The resulting sulfate was reactive to bio-thiols. Cytochrome P450 and sulfotransferases participated in the phase I and phase II reactions, respectively. M1 and M3 were chemically synthesized, and their structures were characterized by mass spectrometry and NMR. The present study has particular value for elucidating the mechanism of liver injury caused by GEM.

Novel Graphene‐Based Foam Composite As a Highly Reactive Filter Medium for the Efficient Removal of Gemfibrozil from (Waste)Water

AbstractGraphene‐based materials have emerged as alternative adsorbents, but their success in removing pharmaceutical contaminants has been limited due to degradation caused by restacking and limited control over their sizes and porosities. Driven by this issue, in the current study, to counteract the restacking behavior, graphene sheets are supported on a thread/rod‐like matrix structure in a boron nitride foam material, and a novel porous composite foam‐supported graphene is synthesized. The as‐prepared novel composite offers extraordinary features, such as high absorption kinetics, large available surface area, high porosity (&gt;98%), ecofriendliness and cost‐effective synthesis, and excellent affinity to emerging pharmaceutical contaminants. When batch‐testing graphene‐based foam material and porous graphene nanosheets to remove gemfibrozil (GEM) from wastewater samples, rapid adsorption kinetics (&lt;5 min) are exhibited by the graphene‐based foam. Column filter studies are conducted for both materials to test their performance in removing GEM from distilled water, synthetic graywater, and actual wastewater. Overall, the foam composite‐based filter marginally outperforms the sand‐supported graphene filter and significantly outperforms the unsupported graphene filter. A numerical MATLAB model is developed to simulate the reactive solute transport of GEM influent through the foam filter. Also, a formal sensitivity analysis is conducted to identify the key parameters influencing the model results.

Enhanced degradation of micropollutants by UV/freshly formed colloidal MnO2: Reactive species, kinetics and pathways

This study reports that freshly formed manganese dioxide (MnO2) is an effective photocatalyst for the abatement of micropollutants, such as nalidixic acid (NDA) and gemfibrozil (GFRZ). The freshly formed MnO2 was flower-like β-MnO2 and showed better efficiency in micropollutant abatement owing to its better adsorption capability than commercial MnO2. Electron paramagnetic resonance (EPR) spectra confirmed that reactive oxygen species (ROS), including hydroxyl radicals (HO•), superoxide radicals (O2•−) and singlet oxygen (1O2), were formed in the UV/MnO2 system. Valence band X-ray photoelectron spectroscopy (VB-XPS) spectra and UV–vis adsorption curves verified the generation of ROS via the reaction between e− and oxygen as the sole pathway. Holes (h+) dominated the degradation of NDA, while both ROS and h+ were important for GFRZ abatement. Side chain cleavage, kentonization and hydroxylation took place in NDA and GFRZ degradation, while demethylation and decarboxylation also occurred during NDA degradation.

Comparative analysis of the removal and transformation of 10 typical pharmaceutical and personal care products in secondary treatment of sewage: A case study of two biological treatment processes

To reduce the occurrence of PPCPs in the environment, its removal in wastewater treatment plants (WWTPs) has attracted much attention. This study reported the removal characteristics of 10 typical PPCPs in two biological treatment processes: blast aeration and UNITANK. The results demonstrated that caffeine (CAF), bezafibrate (BZB), gemfibrozil (GFB), metoprolol (MET), sulfamethoxazole (SMX), and sulfamerazine (SMZ) were mainly removed through biodegradation. Among them, the removal efficiency of CAF was the largest (>85%), and MET was the lowest (<30%). Sulfadiazine (SDZ), naproxen (NPX), sulpiride (SUL), and ofloxacin (OFX) were removed through the combined effect of biodegradation and sludge adsorption. During biotransformation of sulfonamides (SAs), MET, and SUL, some of the conjugates were decomposed into their parent forms again. The results revealed that the adsorption of drugs was correlated with octanol-water partition coefficient (Kow) and electrostatic interaction. The biodegradation efficiency was affected by oxygen supply conditions. The facultative environment, longer sludge retention time (SRT) and hydraulic retention time (HRT) were positively correlated with the removal of most drugs (CAF, SUL, GFB, MET, NPX, OFX, SDZ, SMX). This paper summarized the similarities and differences of drugs’ removal characteristics under different processes and wish to provide useful suggestion for the removal technology of PPCPs in WWTP.

Structural Analysis of Human Serum Albumin in Complex with the Fibrate Drug Gemfibrozil.

Gemfibrozil (GEM) is an orally administered lipid-regulating fibrate derivative drug sold under the brand name Lopid®, among others. Since its approval in the early 80s, GEM has been largely applied to treat hypertriglyceridemia and other disorders of lipid metabolism. Though generally well tolerated, GEM can alter the distribution and the free, active concentration of some co-administered drugs, leading to adverse effects. Most of them appear to be related to the ability of GEM to bind with high affinity human serum albumin (HSA), the major drug-carrier protein in blood plasma. Here, we report the crystal structure of HSA in complex with GEM. Two binding sites have been identified, namely Sudlow’s binding sites I (FA7) and II (FA3–FA4). A comparison of the crystal structure of HSA in complex with GEM with those of other previously described HSA–drug complexes enabled us to appreciate the analogies and differences in their respective binding modes. The elucidation of the molecular interaction between GEM and HSA might offer the basis for the development of novel GEM derivatives that can be safely and synergistically co-administered with other drugs, enabling augmented therapeutic efficacies.

Gemfibrozil, a lipid-lowering drug, reduces anxiety, enhances memory, and improves brain oxidative stress in d-galactose-induced aging mice.

Gemfibrozil (GFZ) is a lipid-lowering drug with several other effects, such as antioxidant and anti-inflammatory activities. In the current study, chronic d-galactose treatment (d-gal, 150 mg/kg/day; i.p., 6 weeks) induced a model of accelerated aging in male mice and was used to study the behavioral, anti-oxidative, and neuroprotective effects of GFZ (100 mg/kg/day; p.o.). Anxiety-like behaviors were assessed using the elevated plus-maze while working memory was measured by spontaneous alternation in a Y-maze. Brain oxidative stress was determined by measuring malondialdehyde (MDA) levels, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Neuropathological evaluation of the brain with hematoxylin-eosin and Masson's trichrome staining was also performed. The results demonstrated that the anxious-like phenotype and the cognitive impairments observed in d-gal-treated mice could be prevented in those animals coadministered with GFZ. Besides, the decrease in SOD and GPx antioxidant enzymatic activities and increase of MDA levels were also prevented in the brains of d-gal plus GFZ treated mice. Preliminary hematoxylin-eosin staining also suggested neuroprotective effects of GFZ. The results of Masson's trichrome staining showed no evidence of fibrosis in brain sections of different experimental groups. The current data provide novel insights into GFZ in the d-galactose-induced aging mouse model that open promising future research lines to determine inflammatory mediators and cell signaling underlying these effects.

Degradation of gemfibrozil in aqueous solutions by gas–liquid dielectric barrier discharge plasma combined with CNTs/γFe2O3

AbstractThe degradation effects and mechanism on gemfibrozil (GEM) in aqueous solution by dielectric barrier discharge (DBD) plasma combined with the catalyst CNTs/γFe2O3 are investigated. The concentrations of plasma‐generated reactive species, including H2O2, O3, , and OH, are measured with spectrophotometric and fluorescent probes. The effects of the plasma treatment period, discharge power, initial GEM concentration, solution pH value, conductivity, and the catalytic property are studied on the degradation rate and energy efficiency. Compared with the sole plasma treatment, CNTs/γFe2O3 could maximally improve the GEM degradation rate and energy efficiency to 99.7% ± 0.2% and 76.5 ± 5.2 mg·kW−1·h−1, respectively. The solution's total organic carbon removal efficiency has been increased to 47.2% ± 2.7%. Meanwhile, the possible degradation pathways of the plasma‐treated GEM solution and overall biological toxicity of GEM degradation intermediates and residual catalyst in solution are investigated.

Transformation of gemfibrozil by the interaction of chloride with sulfate radicals: Radical chemistry, transient intermediates and pathways

The radical chemistry of SO4·– is strongly affected by its interaction with chloride in natural waters, during which SO4·– can be converted to HO· and reactive chlorine species (RCS). This study investigated the effects of chloride on gemfibrozil (GFRZ) transformation via the UV/peroxydisulfate (PDS) process, elucidating the kinetics, degradation pathways and solution toxicity. The pseudo-first-order rate constants (k′) of GFRZ by UV/PDS changed slightly from 1.0 × 10−3 s−1 to 9.3 × 10−4 s−1 as the chloride content increased from 0 to 10 mM because the increase in HO· and RCS levels compensated for the decrease in SO4·– concentration. However, the transformation pathways in the presence of chloride changed significantly. From the transient absorption spectra, we inferred that RCS and SO4·– attacked GFRZ mainly through hydrogen abstraction and/or electron transfer, while HO· interacted with the GFRZ aromatic ring by addition. Hydroxylation, carboxylation and cleavage products were enhanced in UV/PDS/Cl– compared to UV/PDS through the addition of HO· and the cleavage of CO bonds by RCS, and total organic chlorine (TOCl) was undetectable. Interestingly, the acute toxicity was lowest in UV/PDS/Cl–, with an inhibition percentage of 1% at 30 min. The higher inhibition percentages in UV/PDS (13%) and UV alone (53%) at 30 min likely resulted from the stronger capacity of HO· and RCS to oxidize aldehydes to carboxylic groups and cleave CO bonds, respectively, than that of SO4·–. This study provides a better understanding of contaminant transformation mechanisms under UV/PDS treatment at chloride levels present in natural waters.

Comparison of toxic effects of atorvastatin and gemfibrozil on Daphnia magna

Atorvastatin (ATV) and gemfibrozil (GEM) are two typical lipid-lowering pharmaceuticals with different action modes, which are frequently detected in various water bodies owning to their wide usage. However, there is limited information about their effects on Daphnia magna. The present study addressed and compared the toxic effects of ATV and GEM on D. magna through determining the responses of the stress related genes (including Nrf2, Keap1, HO-1, GCLC, p53 and PIG3) in D. magna for 24 h and 48 h acute exposure and the changes of life history traits and swimming behaviors in a 21 days chronic exposure under different concentrations of ATV and GEM exposure (5 μg L−1, 50 μg L−1, 500 μg L−1 and 5000 μg L−1). Results showed that the expression of Nrf2, Keap1, HO-1, GCLC, p53 and PIG3 were induced to various degrees under the ATV exposure. There were similar performances for GEM. ATV and GEM caused the delay of first brooding and hatching time and decrease of eggs production number, especially in GEM exposure, reproduction of Daphnia was significantly inhibited, decreasing 38.51% compared to the control. ATV and GEM increased the heart rate of D. magna, and changed swimming behaviors of D. magna. In summary, two lipid-lowering pharmaceuticals caused oxidative stress on D. magna, subsequently brought about alterations in physiological traits. Comparatively, ATV pose more higher risks to D. magna than GEM, but the detailed action mechanisms of ATV and GEM on D. magna needs more investigations in future.