Iron metal-organic framework nanofiber membrane for the integration of electro-Fenton and effective continuous treatment of pharmaceuticals in water.

In this study, an iron metal-organic framework (Fe-MOF) was synthesized and immobilized by electrospinning technique with the objective of obtaining a membrane composed of nanofibers of this material (Fe-MOF nanofiber membrane). The characterization performed by XRD, TEM, SEM, EDS mapping and FTIR confirmed the correct synthesis of Fe-MOF as well as its correct retention in the elaborated membranes. The usefulness and effectiveness of the Fe-MOF nanofiber membrane as a catalyst for the electro-Fenton process was evaluated by performing sulfamethoxazole degradation tests. Different parameters such as the effect of intensity (25 and 100 mA), the effect of the drug initial concentration (10-50 mg/L) and the reusability of membranes were studied. Then, the degradation of a drug mixture formed by sulfamethoxazole and antipyrine was evaluated, reaching a degradation of 92.10 % and 87.43 % respectively for each drug in 4 h at 25 mA. In addition, the identification of reactive oxygen species was ascertained by scavenger assays. The study of degradation products was also carried out and their toxicity was predicted by ECOSAR program, concluding that the environmental toxicity would disappear with mineralization. Finally, given the good results obtained in batch tests, the behavior of the process was studied in a system that works continuously, achieving a stable degradation of 83.10 % in the case of treatment with a mixture of drugs. This confirmed the stability of the Fe-MOF nanofiber membrane, as well as, its catalytic activity, making it suitable for long-term treatments.

Degradation of antipyrine in water with activated persulfate aided with biochar of olive pomace.

The degradation of antipyrine (AP) in water has been studied using persulfate activated with biochar obtained from gasification of olive pomace (BC) combined with ferric salts in the presence of UV-A radiation. Firstly, the adsorption of AP on biochar was evaluated. The data were adjusted using various kinetic models verifying that AP adsorption on BC occurs in three stages and follows pseudo-second order kinetics. Degradation tests show that the presence of iron or persulfate (PS) in binary systems with BC produces increases AP degradation when no radiation is used, reaching 75.7 % due to the ability of BC to donate electrons. On the other hand, addition of PS showed an increase in efficiency in the presence of BC (up to 79%). For ternary systems the best result was found when UVA/PS/Fe was used (100% of AP degradation in 30 min). The addition of UV-A radiation to the BC/PS system improves the degradation of the contaminant by only 6.7%, while the presence of iron in the studied conditions does not cause any improvement. A Central Composite Factorial Design of experiments was used to optimize the UVA/BC/PS/Fe system, leading to an 89.3% AP degradation rate in 90 min (k = 0.0134 min-1) under optimal conditions ([Fe(III)] = 10 mg/L, [PS] = 379 mg/L, [BC] = 500 mg/L). Although the best results were obtained for the UVA/PS/Fe process without BC, systems based on BC/PS can be considered as an alternative in cloudy days or when simple processes are selected due to economical/technical reasons.

Design, Synthesis and Antibacterial Assessment of Active (4-Arylazo-3-Methyl-2-Thienyl) 4-Antipyrine Ketones.

The chemicals formed from antipyrines are flexible organic building blocks that are employed in the development of pharmaceuticals. By diazotizing (4-arylazo-3-hydroxy-2-thienyl) 4-antipyrine ketones 1a, 1b and 1c and (4-arylazo-3-methyl-2-thienyl) 4-antipyrine ketones (2a, 2b and 2c) further replaced with six other coupling components, a broad spectrum of hybrid molecules have been created. Mass spectra, NMR, FTIR, and elemental analyses have all been used to confirm the structures of the synthesised compounds. The antimicrobial screening was investigated by agar well diffusion and diluting the broth technique against both Gram-negative and positive-tested bacterial strains. (3-methyl-5-(phenylamino)-4-(4-tolylazo)-2-thienyl) 4-antipyrine ketone (2a) was found to be superior to Ciprofloxacin against test strains: Acinetobacter sp (34.33±1.15 mm), Listeria monocytogenes (29.33±1.15 mm) and Streptococcus sp. (19.33±1.15 mm). Also, good to moderate activities were expressed as minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) which were recorded at 9±1 to 59.67±4.51 µg/mL and 16±4 to >512 µg/mL, respectively, using compounds 2a, 2b, and 2c. MBC/MIC ratio showed, that only, 2a and 2b have a bactericidal effect but other antipyrines with bacteriostatic strength. To conclude, it was suggested that the use of these novel synthesized (4-arylazo-3-methyl-2-thienyl) 4-antipyrine ketone derivatives molecules as a new chemical class of antimicrobial agents to perform new drug discovery in pharmaceutical preparations and medicinal research.

Evaluation of acetanilide and antipyrine adsorption on lignin-derived activated carbons.

In this study, the removal of two emerging pollutants (EPs), antipyrine and acetanilide, through adsorption on activated carbons (ACs) prepared by chemical activation of Organosolv lignin with H3PO4 were evaluated. ACs with different pore size distribution were obtained at different impregnation ratios (H3PO4/lignin, 0.5-3.0 w/w) and activating temperatures (500-900 °C). The porosity and surface chemistry of the ACs were determined, and a bimodal size distribution of micropores and narrow mesopores was observed for the different ACs. These ACs were tested for antipyrine and acetanilide adsorption in aqueous solutions in a batch system at 20 °C and low concentration levels (0.5-10 ppm). In general, the ACs exhibited higher adsorption affinity to acetanilide than to antipyrine due to its smaller molecular size. Langmuir adsorption isotherm was able to describe the adsorption equilibrium data. A new Linear Driving Force (2-LDF) kinetic model, based on the bimodal size distribution of micropores and narrow mesopores observed for the ACs has been developed. The new model provided a more accurate description of the batch adsorption rates than that obtained from conventional kinetic models, and also enabled to relate the pore size distribution of the adsorbent with the adsorption kinetics. The validity of this model was checked in small-scale column fixed bed adsorption for the AC showing the highest affinity for both EP. The kinetic model and equilibrium adsorption isotherm obtained from the batch experiments were successfully used to provide an accurate description of the bed service time and the full breakthrough profile of acetanilide and antipyrine.

Heterogeneous electro-Fenton system using Fe-MOF as catalyst and electrocatalyst for degradation of pharmaceuticals.

In recent years, heterogeneous electro-Fenton processes have gained considerable attention as an alternative to homogeneous processes. In this context, the aim of this study is the use of a commercial iron metal-organic framework (Fe-MOF), Basolite® F-300, as a base material for the design of a heterogeneous electro-Fenton treatment system for the removal of antipyrine. Initially, the catalyst was applied as powder in aqueous solution and three key parameters of the electro-Fenton process (pH, Fe-MOF concentration and current density) were evaluated and optimized by a Central Composite Design Face Centred (CCD-FC) using antipyrine removal and energy consumption as response functions. Near complete antipyrine removal (94%) was achieved under optimal conditions: pH 3, Fe-MOF 157.78 mg/L and current density 6.67 mA/cm2, obtaining an energy consumption of 0.29 W·h per mg of antipyrine removed. Later, two electrocatalysts (Fe-MOF functionalized cathodes), prepared by different Fe-MOF immobilisation approaches (composite of carbon black/polytetrafluoroethylene or by electrospinning on Ni foam), were synthesized. Their characterisation showed notable Fe-MOF incorporation into the material and favourable properties as electrocatalysts. Both Fe-MOF functionalized cathodes were evaluated in the removal of antipyrine at different pH (acidic and natural) and current density (27.78 and 55.56 mA/cm2), achieving in the best conditions removal levels around 80% in 1 h without any operational problems. In addition, several intermediates generated during the treatment were identified and their toxicity estimated. According to the obtained results, the degradation compounds have less toxicity than the parent compounds, confirming the effectiveness of the treatment.

Molecular docking and simulation studies of some pyrazolone-based bioactive ligands targeting the NF-κB signaling pathways.

NF-κB has become a predominant regulator responsible for multiple physiological and pathological processes. NF-κB signaling pathway has canonical and non-canonical components which strategize the cancer-related metabolic processes. Non-canonical NF-κB pathways are known to contribute towards the chemoresistance of cancer cells. Consequently, NF-κB can be utilized as a potential therapeutic target for modifying the behaviour of tumor cells. In view of this, we herein report a series of pyrazolone-based bioactive ligands that potentially target NF- κB and, thereby, unveil their anticancer properties. The pharmacological screening of the synthesized compounds were carried out using various virtual screening techniques. The anticancer studies of synthesized pyrazolones showed that APAU exhibited the most potent effect against the MCF-7 cells with an IC50 value of 30 µg/ml. Molecular docking studies revealed that the pyrazolones inhibited cell proliferation by targeting the NFκB signaling pathway. The molecular dynamics simulation studies predicted the stability and flexibility of pyrazolone-based bioactive ligands.

Activity and stability of bifunctional perovskite/carbon-based electrodes for the removal of antipyrine by electro-Fenton process.

Bifunctional perovskite/carbon-black(CB)/polytetrafluoroethylene(PTFE) electrodes for electro-generation and catalytic decomposition of hydrogen peroxide to oxidizing hydroxyl radicals have been fabricated. These electrodes were tested for electroFenton (EF) removal of antipyrine (ANT) as a model antipyretic and analgesic drug. The influence of the binder loading (20 and 40 wt % PTFE) and type of solvent (1,3-dipropanediol and water) was studied for the preparation of CB/PTFE electrodes. The electrode prepared with 20 wt % PTFE and water exhibited a low impedance and remarkable H2O2 electro-generation (about 1 g/L after 240 min, a production rate of ca. 6.5 mg/h·cm2). The incorporation of perovskite on CB/PTFE electrodes was also studied following two different methods: i) direct deposition on the CB/PTFE electrode surface and ii) addition in the own CB/PTFE/water paste used for the fabrication. Physicochemical and electrochemical characterization techniques were used for the electrode's characterization. The dispersion of perovskite particles in the own electrode matrix (method ii) exhibited a higher EF performance than the immobilisation onto the electrode surface (method i). EF experiments at 40 mA/cm2 and pH 7 (non-acidified conditions) showed ANT and TOC removals of 30% and 17%, respectively. The increase of current intensity up to 120 mA/cm2 achieved the complete removal of ANT and 92% of TOC mineralisation in 240 min. The bifunctional electrode also proved high stability and durability after 15 h of operation.

Glucose determination in human serum by applying inner filter effect quenching mechanism of upconversion nanoparticles.

Accurate blood glucose determination is essential to the clinical diagnosis and management of diabetes. This work establishes an inner filter effect (IFE) strategy between upconversion nanoparticles (UCNPs) and quinone-imine complex for glucose monitoring in human serum simply and efficiently. In this system, the enzyme glucose oxidase (GOx) catalyzes the reaction of glucose into hydrogen peroxide (H2O2) and gluconic acid when compulsion by oxygen. In the presence of horseradish peroxidase (HRP), the produced H2O2 can catalytically oxidize phenol and 4-amino antipyrine (4-AAP) to generate quinone-imine products. The purple-colored quinone-imine complex effectively absorbed the fluorescence of NaYF4:Yb3+, Er3+ UCNPs, leading to the strong fluorescence quenching of UCNPs through IFE. Thus, a new approach was established for glucose monitoring by determining the fluorescence intensity. Under the optimal condition, this approach shows better linearity to glucose from 2-240 µmol/L with a low detection limit at 1.0 µmol/L. Owing to the excellent fluorescence property and background-free interference of the UCNPs, the biosensor was applied for glucose measurements in human serum and got a satisfactory result. Furthermore, this sensitive and selective biosensor revealed great potential for the quantitative analysis of blood glucose or different kinds of H2O2-involved biomolecules for the application of clinical diagnosis.

Design, synthesis, and biological investigation of oxadiazolyl, thiadiazolyl, and pyrimidinyl linked antipyrine derivatives as potential non-acidic anti-inflammatory agents.

A novel series of 12 antipyrine derivatives containing 1,3,4-oxadiazoles (4a-d), 1,3,4-thiadiazoles (6a-d), and pyrimidines (8a-d), was preparedand assessed for its potential in vitro COX-2 inhibitors. Compared to Celecoxib, compounds 4b-d and 8d were the most potent derivatives c with a half-maximal inhibitory concentration range of 53-69 nM. Considering COX-2 selectivity index, compounds 4 b and 4c were chosen among these most potent derivatives for further investigation. The in vivo ability of compounds 4 b and 4c to counteract carrageenan-induced paw edoema has been assessed and their potential underlying mechanisms have been elucidated and the results have been further validated using molecular docking simulations.

Highly Sensitive and Selective Detection of Melatonin in Biofluids by Antipyrine Based Fluorophore.

A simple fluorescent based organic fluorophore was synthesized and it shows significant fluorescent intensity with melatonin (MLN). Hence, it was applicable to the detection of MLN by colorimetric and fluorimetric techniques at neutral pH. Under optimized experimental condition, the synthesized organic fluorophore detects MLN selectively in the presence of other interfering biomolecules through ICT mechanism. The melatonin sensing mechanism is supported by DFT and 1H-NMR titration. Based on the findings, this method can be applied to design a simple clinical diagnostic tool for MLN.

Self-Assembled Structure of α-Isostearyl Glyceryl Ether Affects Skin Permeability-a Lamellar with 70-nm Spaces and L3 Phase Enhanced the Transdermal Delivery of a Hydrophilic Model Drug.

Self-assembled surfactant structures, such as liquid crystals, have the potential to enhance transdermal drug delivery. In the present study, the pseudo-ternary system of GET (composed of α-Isostearyl glyceryl ether (GEIS) and polysorbate 60)/1,3 butanediol (BG)/water) was shown to exhibit a complex phase diagram. Small- and wide-angle X-ray scattering (SWAXS) and freeze-fracture transmission electron microscopy (FF-TEM) revealed that GET6BG60 (6%GET/60%BG/34%Water) formed a lamellar phase with a repeated distance of approximately 72 nm. Such a long-repeated distance of the lamellar phase was unique in the surfactant system. Moreover, the various structures, such as multilamellar vesicles and branched-like layers, were observed, which suggested that they might be deformable. On the other hand, only core-shell particles were observed in GET6BG20, the core of which was an L3 phase. GET6BG20 and GET6BG60 significantly enhanced the skin permeation of the hydrophilic model drug, antipyrine (ANP) (log Ko/w, - 1.51). However, their permeation profiles were distinct. Liquid chromatography-tandem mass spectrometry revealed that epidermal accumulation of GEIS was significantly higher with GET6BG60 than GET6BG20 after 1.5 h of permeation, which might be attributed to differences in their deformable properties. Furthermore, GEIS was reported to affect intercellular lipids. Accumulated GEIS in the epidermis may have interacted with intercellular lipids and enhanced the transdermal delivery of ANP. The difference in the permeation profiles of ANP may be attributed to the penetration process of GEIS in the epidermis. This study suggests that GET6BG20 and GET6BG60 are unique carriers to enhance the permeation of hydrophilic drugs, such as ANP.

Peroxymonosulphate Activation by Basolite® F-300 for Escherichia coli Disinfection and Antipyrine Degradation.

In this study, the removal of persistent emerging and dangerous pollutants (pharmaceuticals and pathogens) in synthetic wastewater was evaluated by the application of heterogeneous Advanced Oxidation Processes. To do that, a Metal-Organic Framework (MOF), Basolite® F-300 was selected as a catalyst and combined with peroxymonosulfate (PMS) as oxidants in order to generate sulphate radicals. Several key parameters such as the PMS and Basolite® F-300 concentration were evaluated and optimized using a Central Composite Experimental Design for response surface methodology for the inactivation of Escherichia coli. The assessment of the degradation of an analgesic and antipyretic pharmaceutical, antipyrine, revealed that is necessary to increase the concentration of PMS and amount of Basolite® F-300, in order to diminish the treatment time. Finally, the PMS-Basolite® F-300 system can be used for at least four cycles without a reduction in its ability to disinfect and degrade persistent emerging and dangerous pollutants such as pharmaceuticals and pathogens.

Design of imprinting matrix for dual template sensing via electropolymerized polythiophene films.

This work presents the design of 3-thiophene acetic acid (3-TAA) polymer matrix based molecularly imprinted polymer (MIP)/reduced graphene oxide (RGO) composite for sensitive and selective detection of antipyrine (AnP) and ethionamide (ETH) simultaneously. Dual drug embedded molecularly imprinted polymer (MIP) based electrochemical sensor was developed via electropolymerization of 3-TAA. AnP and ETH were embedded inside a polymer matrix based on their 3-D orientation and interaction(s) with functional monomer(s). Their extraction from polymeric matrix generates cavities complimentary to shape and size of AnP and ETH. The extraction of templates was confirmed by differential pulse voltammetry (DPV) as well as high-performance liquid chromatography (HPLC). The designed sensor selectively captures and produces the electrochemical signal for imprinted drugs. The electrochemical behaviour of AnP and ETH was investigated by DPV technique. The sensitivity for both drug molecules was commendable on a single polymeric composite with RGO on GC electrode (LOD of 0.117 µM for AnP and 0.15 µM for ETH). Also, the sensor exhibited excellent selectivity towards AnP and ETH in the presence of other analogous interferent molecules. Thus, the designed sensor showed high sensitivity as well as high selectivity for imprinted dual drug molecules on a single platform.

Prolonged Delivery of Apomorphine Through the Buccal Mucosa, Towards a Noninvasive Sustained Administration Method in Parkinson's Disease: In Vivo Investigations in Pigs.

In the current work, prolonged systemic delivery of apomorphine via buccal mucosa was shown to be a promising treatment for Parkinson's disease as a substitute for clinically utilized subcutaneous infusions. Due to extensive 'first-pass' metabolism, apomorphine is administered parenterally to bypass liver metabolism. Drawbacks of parenteral administration cause low patient compliance and adherence to treatment. On the other hand, while also bypassing the liver, delivery through buccal mucosa has a superior safety profile, is less costly, lacks pain and discomfort, and possesses excellent accessibility, overall augmenting patient compliance. Current in vivo study in pigs showed: (1) steady plateau levels of apomorphine in plasma were obtained 30 min following administration and remained constant for 8 h until a delivery device was removed, (2) bioavailability of apomorphine was 55%-80% as opposed to <2% peroral and (3) simulation of the pharmacokinetic profile obtained in pigs predicted therapeutically relevant levels of apomorphine in human. Furthermore, antipyrine was incorporated as a permeation marker to enable mechanistic investigation of apomorphine release from the delivery device and its permeation through the buccal mucosa. In addition, limitations of an Ussing diffusion chamber as an ex vivo research tool were also discussed.

Removal of antipyrine through two-dimensional and three-dimensional electrolysis: comparison, modification, and improvement.

In this work, removal of antipyrine was studied through two-dimensional (2D) and three-dimensional (3D) electrolysis. 2D electrolysis was firstly studied with the Ti/SnO2-Ta2O5-IrO2 anode as working electrode. Operating parameters affecting antipyrine removal, such as current density, electrode distance, and initial concentration of antipyrine, were investigated and optimized. As the limited antipyrine removal efficiency of 48.0% was not satisfying, 3D electrolysis with γ-Al2O3 as particle electrodes was introduced in the purpose of improving the antipyrine removal. An obviously enhanced removal efficiency of 78.3% was obtained, which seemingly validated the effect of particle electrodes in improving antipyrine removal. Hence, an effort to further enhance the antipyrine removal efficiency was made through improving the electrochemical characteristics of γ-Al2O3 as particle electrodes. Modified Sn-Sb-Bi/γ-Al2O3 particles were thus prepared through impregnation method. And a desirable antipyrine removal efficiency of 94.4% and energy consumption of 0.18 kWh/g antipyrine were achieved in the 3D electrolysis with Sn-Sb-Bi/γ-Al2O3 as particle electrodes. Furthermore, possible mechanism and pathway of antipyrine degradation in 3D electrolysis were explored through detection of ·OH using terephthalic acid fluorescent probe method and detection of antipyrine degradation intermediates using LC-MS.

4-Methylamino antipyrine determination in human plasma by high-performance liquid chromatography tandem mass spectrometry.

In the present study, a simple and rapid method for metamizole metabolite 4-methylamino antipyrine (MAA) determination in human plasma was developed, validated and successfully applied to a clinical trial. Chromatographic separation was achieved in HILIC mode on a YMC-Pack SIL column (100 × 2.0 mm; S-5 µm, 30 nm), with a mobile phase consisting of acetonitrile, water and formic acid. Protein precipitation of a small plasma volume using acetonitrile was selected for sample preparation. The multiple reaction monitoring transitions in the positive ionization mode were m/z 218.2 → 56.2 for MAA and m/z 221.2 → 56.2 for MAA-d3 (IS, internal standard). Concentration levels of MAA calibration standards were in the range of 0.100-20 µg/ml. Metamizole conversion into MAA in both water and organic media was investigated, and the level of the conversion in commercially available injection solutions was estimated.

Removal of emerging pollutants in aqueous phase by heterogeneous Fenton and photo-Fenton with Fe2O3-TiO2-clay heterostructures.

Fe2O3-TiO2-clay heterostructures have been prepared using an organo-bentonite as support, which organophilic character favored the fixation of TiO2. Furthermore, Fe2O3 was successfully anchored by wet impregnation. The resulting materials are characterized by a disordered layered structure and a mesoporous texture. The heterostructures were employed as catalysts for the removal of two pharmaceuticals, acetaminophen (ACE) and antipyrine (ANT), by heterogeneous Fenton and photo-Fenton processes. ACE removal under different operation conditions was studied in detail to establish structure-performance relationships, being the TiO2 formation and the developed texture the main factors controlling the activity. ANT showed a higher refractory behavior in oxidation by Fenton. Among the technologies studied, heterogeneous photo-Fenton achieved the best catalytic performance and higher kinetic rate and mineralization degree. Iron leaching was very low, lower than 5% of the initial iron load in all cases. This work demonstrates the potential application of these heterostructures for the removal of emerging pollutants of different nature.

Solvothermal synthesis of multiwall carbon nanotubes/BiOI photocatalysts for the efficient degradation of antipyrine under visible light.

Antipyrine (ANT), as a widely used relieve headache, fever anti-inflammatory pharmaceutical in medical treatment, is difficult to be removed completely in water. The application of photocatalytic removal of ANT is restricted to UV light irradiation (<5% of solar energy), and the degradation pathways of ANT require more theoretical evidence. In this study, a series of three dimensions (3D) hierarchical structure multiwall carbon nanotubes/bismuth oxyiodide (MWCNTs/BiOI) photocatalysts were systematically designed and firstly applied to remove ANT through visible light (>43% of solar energy) induced photodegradation. Consequently, the as-prepared MWCNTs/BiOI photocatalysts presented superior photocatalytic activities on ANT degradation with respect to that of BiOI under 60 min visible light irradiation (100% vs 82.2%). Especially, the enhanced photocatalytic mechanism on ANT was analyzed by morphology, optical and photo-electrochemical properties. Results revealed that the designed 3D micro-mesoporous structure could promote the diffusion of photogenerated electron-hole pairs, and the utilization of photoelectrons could be efficiently improved by MWCNTs (1.5 times). Furthermore, based on radicals scavenging experiments, the photogenerated hole (h+) and superoxide radical (O2-) were demonstrated as the dominant active species in ANT photocatalytic oxidation process. The photodegradation pathways of ANT were proposed with the calculation of frontier electron densities (FEDs) and the analysis of LC-MS/MS. This study presents a feasible approach for the high efficiency removal of trace pharmaceuticals under visible light photocatalytic process.

Activities of metabolizing enzymes in human placenta.

In addition to the transfer across the placenta, placenta displays hormonal and xenobiotic metabolism, as well as enzymatic defense against oxidative stress. We analyzed aromatase (CYP19A1), uridine 5'-diphospho-glucuronyltransferase (UGT), glutathione-S-transferase (GST) and catalase (CAT) activities in over 70 placentas from nonsmokers stored at -80 °C from former perfusion studies. A wide interindividual variation in all activities was found. Longterm storage at -80 °C did not affect the activities. Ethoxyresorufin-O-deethylase (EROD, CYP1A1) was not detected in any of the studied placentas perfused with chemicals. Several compounds in placental perfusion changed statistically significantly the enzyme activities in placental tissue. Melamine and nicotine increased CYP19A1, melamine increased UGT and GST, PhIP with ethanol decreased CYP19A1 and increased GST, and PhIP with buprenorphine decreased CAT. Antipyrine in 100 µg/ml also changed the studied enzyme activities, but not statistically significantly. Because antipyrine is a reference compound in placental perfusions, its potential effects must be taken into account in human placental perfusion. Enzyme activities deserve further studies as biomarkers of placental toxicity. Finally, enzyme activities deserve further studies as biomarkers of placental toxicity.

CYP3A Polymorphism and Chronic Mercury Intoxication.

We analyzed the relationship between polymorphic loci of CYP3A genes (CYP3A4 (rs2740574), CYP3A5 (rs776746) and CYP3A7 (rs2257401)) with the development of chronic mercury intoxication. Of 170 men examined, 120 were workers chronically exposed to mercury vapors and 50 were carriers of GG-HSPA1B (+1267A/G) genotype associated with chronic mercury intoxication. Urinary content of 4-hydroxyantipyrine (4-HAP) generated in the reaction predominantly catalyzed by CYP3A4/CYP3A5 was studied in workers without chronic mercury intoxication (group 1, N=46) and patients in the delayed period of chronic mercury intoxication (group 2, N=74) depending on the genotypes of CYP3A4 and CYP3A5. For polymorphic loci CYP3A5 and CYP3A7, a tendency to an increase in the frequency of genotypes with rare alleles was found (p=0.071 and p=0.078) in the combined group (group 2 together with GGHSPA1B genotype carriers) relative to group 1. The high level of linkage disequilibrium was noted, especially for the pair rs776746 and rs2257401 (LD (r)=0.89). In group 2, a trend to 4-HAP decrease compared to group 1 (p=0.056 and p=0.065) was revealed for carriers of AA-CYP3A4 and GG-CYP3A5 genotypes. The involvement of CYP3A in the development of mercury neurotoxic effect remains unclear.