Acetaminophen Elimination Research Articles

TiO2/Polysulfone Composite Membrane for Enhanced Removal of Acetaminophen from Water

There has been a significant rise in the worldwide usage of acetaminophen (ACT), particularly after the COVID-19 pandemic, leading to concerns regarding its possible discharge into the environment. Even at low levels, the gradual buildup of ACT can present a significant risk to both aquatic ecosystems and human health, especially when consumed through drinking water. The advanced oxidation process (AOP) is an excellent treatment technique for removing ACT. However, it is a complex and expensive procedure that consumes a significant amount of energy. Membrane technology has evolved as a viable and efficient method to eliminate ACT, offering a simpler and more energy-efficient approach. This study examined the impact of different concentrations of titanium dioxide (TiO2) nanofiller on the elimination of ACT from a water-based solution. The membrane containing the highest concentration of TiO2 (2 wt.%) demonstrated the greatest water flux and ACT removal rate at 32 L/m2h and 97%, respectively. The inclusion of TiO2 had a substantial impact on the structure of the membrane, leading to the formation of evenly distributed finger-like pores throughout a spongy framework. This modification resulted in enhanced flow rate and increased efficiency in terms of the flux and rejection rate

Strong enhancement on acetaminophen elimination and effective control of chlorinated/brominated by-products generation in heat/peroxymonosulfate system with sodium perborate

The application of heat/peroxymonosulfate (PMS) system was severely constrained due to the high O–O bond dissociation energy of PMS and the high risk of forming halogenated by-products. Interestingly, this work found that sodium perborate (NaBO3) could significantly improve the removal of acetaminophen in heat/PMS system. The proposed NaBO3/heat/PMS system could achieve 100 % elimination efficiency of ACT within 15 min and exhibited an excellent pseudo-first-order rate constant (kobs), which was 35.6-folds higher than heat/PMS system. 1O2 and OH were identified as the primary reactive species in NaBO3/heat/PMS system. NaBO3 can hydrolyze to produce BO2− and H2O2, where BO2− can subsequently hydrolyze to generate B(OH)4− having strong buffer capacity. The HOOB(OH)3/HOOBO, characterized by their asymmetric O–O bonds, can be formed through the reaction of PMS with BO2− and B(OH)4−. 1O2 mainly originated from the reactions of PMS with the formed HOOB(OH)3/HOOBO, and OH primarily originated from the cleavage of O–O bond in HOOB(OH)3/HOOBO and PMS. Three removal pathways of acetaminophen were proposed. The toxicity of acetaminophen solution was reduced following the treatment using NaBO3/heat/PMS system. Humic acid, CO32−, Br− and Cl− suppressed the acetaminophen removal in NaBO3/heat/PMS system, while initial pH, NO3− and SO42− had minimal impact. Notably, the kobs of acetaminophen removal in actual waters (e.g., groundwater and lake water) were greater than that in ultrapure water. More importantly, NaBO3/heat/PMS system can effectively control the formation of chlorinated/bromine by-products, which was achieved by converting HClO to inert B(OH)3OCl− with B(OH)4−, and reducing the HBrO and HClO to Br– and Cl– with deprotonated H2O2 (HO2−). This study proposed a promising approach for improving heat/PMS system and underscored its application potential in treating water containing Cl−and Br−.

Peanut-shell-derived biochar mediated peracetic acid activation for the elimination of acetaminophen via an electron-transfer regime

Biochar-based heterogeneous activation of disinfectant peracetic acid (PAA) is an attractive and promising route for micropollutant elimination in water, yet the underlying activation mechanism is still scarce. In this study, PAA was first catalyzed by peanut shell-derived biochar (PSBC) to degrade acetaminophen (ACP). The enhancement of ACP removal was triggered by PAA activation, while the coexisted H2O2 was unexpected to be an adverse factor owing to its occupation of active sites. Higher dosages of PSBC (0–0.30 g/L) and PAA (0–4.0 mM) favored the destruction of ACP, and the activation energy (41.8 kJ/mol) of PSBC/PAA system is lower than that of the thermal or microwave activated PAA system. The experimental results demonstrate that the metastable complex PSBC-PAA* dominated ACP elimination through an electron transfer mechanism. The surface –OH group was validated to be the key active site for PAA activation. Surprisingly, the actual water matrices present a negligible effect and the promotion of HCO3− ion on ACP removal was even observed. Based on the identified intermediates, the transformation of ACP was further proposed with the formation of polymeric products via oxidative coupling reactions. The findings not only shed light on the mechanism of PAA activated by the biochar-based catalyst but also contribute to a novel perspective on future PAA studies in contamination remediation.

Synergistic effects of layered Ti3C2TX MXene/MIL-101(Cr) heterostructure as a sonocatalyst for efficient degradation of sulfadiazine and acetaminophen in water

In this work, different mass loadings of MXene-coupled MIL-101(Cr) (MXe/MIL-101(Cr)) nanocomposites were generated through a hydrothermal process in order to investigate the potential of this nanocomposite as a novel sonocatalyst for the elimination of sulfadiazine (SD) and acetaminophen (AAP) in aqueous media. The sonocatalytic activity of different MXe/MIL-101(Cr) compositions and surface functionalities was investigated. In addition, the sonocatalytic activities at various pH values, temperatures, pollutant concentrations, catalyst dosages, initial H2O2 concentrations, and organic matter contents were investigated. The experiments on the sonocatalytic elimination of SD and AAP revealed that MXe/MIL-101(Cr) exhibited a catalytic efficiency of ∼ 98% in 80 min when the MXene loading was 30 wt% in the nanocomposite. Under optimized reaction conditions, the degradation efficiency of MXe/MIL-101(Cr) reached 91.5% for SD and 90.6% for AAP in 60 min; these values were 1.2 and 1.8 times greater than those of MXene and MIL-101(Cr), respectively. The high surface area of the MXe/MIL-101(Cr) nanocomposite increased from 4.68 m2/g to 294.21 m2/g, and the band gap of the tagged MIL-101(Cr) on the MXene surface was minimized. The superior sonocatalytic activity of MXe/MIL-101(Cr) was attributed to the effective contact interface, the effective separation rate of e- − h+ pairs through the type II heterostructure interface, and the favorable high free •OH radical production rates that promoted the degradation of SD and AAP. The solid heterointerface between MIL-101(Cr) and MXene was confirmed through Raman and FTIR analysis and was found to promote accessible •OH radical production under sonication, thus maximizing the catalytic activity of nanocomposites. The present results present an effective strategy for the design of a highly efficient, low-cost, reliable sonocatalyst that can eradicate pharmaceutical pollutants in our environment.

Possibilities and Limitations of the Sono-Fenton Process Using Mid-High-Frequency Ultrasound for the Degradation of Organic Pollutants.

Mid-high-frequency ultrasound (200-1000 kHz) eliminates organic pollutants and also generates H2O2. To take advantage of H2O2, iron species can be added, generating a hybrid sono-Fenton process (sF). This paper presents the possibilities and limitations of sF. Heterogeneous (a natural mineral) and homogeneous (Fe2+ and Fe3+ ions) iron sources were considered. Acetaminophen, ciprofloxacin, and methyl orange were the target organic pollutants. Ultrasound alone induced the pollutants degradation, and the dual competing role of the natural mineral (0.02-0.20 g L-1) meant that it had no significant effects on the elimination of pollutants. In contrast, both Fe2+ and Fe3+ ions enhanced the pollutants' degradation, and the elimination using Fe2+ was better because of its higher reactivity toward H2O2. However, the enhancement decreased at high Fe2+ concentrations (e.g., 5 mg L-1) because of scavenger effects. The Fe2+ addition significantly accelerated the elimination of acetaminophen and methyl orange. For ciprofloxacin, at short treatment times, the degradation was enhanced, but the pollutant complexation with Fe3+ that came from the Fenton reaction caused degradation to stop. Additionally, sF did not decrease the antimicrobial activity associated with ciprofloxacin, whereas ultrasound alone did. Therefore, the chemical structure of the pollutant plays a crucial role in the feasibility of the sF process.

Boosted Activity of g-C3N4/UiO-66-NH2 Heterostructures for the Photocatalytic Degradation of Contaminants in Water.

The combination of graphitic carbon nitride and the metal-organic framework UiO-66-NH2 has been developed with the aim to enhance the photocatalytic activity of pure semiconductors. Different proportions of g-C3N4 and UiO-66-NH2 were combined. Complete characterization analysis of the resulting photocatalytic materials was conducted, including N2 adsorption isotherms, XRD, FTIR, STEM-EDX microscopy, DRS-UV-visible, and photoluminescence. The photocatalytic activity was tested in an aqueous solution for the removal of acetaminophen as the target pollutant. From the obtained results, less than 50% of UiO-66-NH2 incorporated in the g-C3N4 structure enhanced the photocatalytic degradation rate of both bare semiconductors. Concretely, 75% of g-C3N4 in the final g-C3N4/UiO-66-NH2 heterostructure led to the best results, i.e., complete acetaminophen elimination initially at 5 mg·L-1 in 2 h with a pseudo-first order rate constant of ca. 2 h-1. The presence of UiO-66-NH2 in the g-C3N4 enhanced the optoelectronic properties, concretely, the separation of the photo-generated charges was improved according to photoluminescence characterization. The better photo-absorption uptake was also confirmed by the determination of the quantum efficiency values of the heterostructure if compared to either pure g-C3N4 or UiO-66-NH2. This photocatalyst with the best activity was further tested at different pH values, with the best degradation rate at a pH close to the pHpzc ~4.15 of the solid. Sequential recycling tests demonstrated that the heterostructure was stable after five cycles of use, i.e., 15 h. A high contribution of photo-generated holes in the process of the degradation of acetaminophen, followed marginally by superoxide radicals, was suggested by scavenger tests.

Sodium tetraborate simultaneously enhances the degradation of acetaminophen and reduces the formation potential of chlorinated by-products with heat-activated peroxymonosulfate oxidation

In this study, sodium tetraborate (Na2B4O7) was introduced to enhance the degradation of acetaminophen (ACT) in heat-activated peroxymonosulfate (PMS) process. The elimination of ACT in Na2B4O7/heat/PMS process followed the pseudo-first order kinetics. The corresponding kobs value with 10 mM Na2B4O7 was 33.1 times higher than that in heat/PMS process. 1O2 and HO· were identified as primary reactive species via quenching experiments and electron paramagnetic resonance technology. B(OH)4−, the hydrolysis product of Na2B4O7, reacted with PMS to generate HOOB(OH)3−. 1O2 was generated by the self-decomposition of PMS using B(OH)4− as catalyst, while HO· was produced via the breakage of peroxide bond of PMS and HOOB(OH)3−under high temperature. ACT was degraded by reactive species via the pathways of -NH- bond breakage, -OH replacement, -NH2 oxidation and benzene ring cleavage. Nine transformation intermediates were detected by LC/Q-TOF/MS, and the toxicity of reaction solution decreased significantly with the elimination of ACT. Increasing Na2B4O7 dosage, PMS concentration, initial pH and reaction temperature were conducive to ACT elimination. Humic acid, Cl− and CO32− inhibited the degradation of ACT heavily, while SO42− and NO3− had the negligible effects. Moreover, B(OH)4− could react with free chlorine to the inert B(OH)3OCl− and further significantly suppress the formation of chlorinated by-products for the treatment of Cl−-containing water in Na2B4O7/heat/PMS process. This study provided an effective way to enhance the oxidation capacity of heat/PMS process and suppress the formation of chlorinated by-products in chloride-containing water, and the findings had important implications for using borate buffer in the studies of PMS-based advanced oxidation processes.

Elimination of acetaminophen in sodium carbonate-enhanced thermal/peroxymonosulfate process: Performances, influencing factors and mechanism

Peroxymonosulfate (PMS) is commonly poor for degrading organic contaminants through thermal activation because of the high O-O bond dissociation energy. This work is the first to demonstrate that sodium carbonate (Na2CO3) significantly promoted the degradation of acetaminophen with thermal/PMS process, and Na2CO3/thermal/PMS process exhibited faster removal rate of acetaminophen and a lower formation potential of BrO3− than Na2CO3/thermal/peroxydisulfate process. The increase of Na2CO3 dosage, PMS dosage and reaction temperature were favorable for acetaminophen degradation with Na2CO3/thermal/PMS process. Na2CO3/thermal/PMS process could generate multiple reactive species including 1O2 and the radicals of ·OH, SO4·− and CO3·−. 1O2 was dominant in acetaminophen removal regardless of the dosage of Na2CO3, while the radicals of ·OH, SO4·− and CO3·− also participated in the removal of acetaminophen. Three different degradation pathways of acetaminophen were proposed based on UPLC-Q-TOF-MS detection, and the toxicity towards luminescent bacteria and green algae significantly decreased. Humic acid slightly inhibited the removal of acetaminophen, sulfate ion and nitrate ion presented negligible effect on acetaminophen removal, while chloride ion and bromide ion greatly accelerated the elimination of acetaminophen. Na2CO3/thermal/PMS process exhibited wide suitability in eliminating acetaminophen in ground water and degrading other organic contaminants, including bisphenol A, naproxen, diclofenac, rhodamine B and acid orange 7. This work provided a promising method to enhance the oxidizing ability of thermal/PMS process and might promote its application in the remediation of contaminated water and soil.

Indirect electrochemical degradation of acetaminophen: process performance, pollutant transformation, and matrix effects evaluation

Acetaminophen (ACE), a highly consumed pharmaceutical, was degraded in aqueous matrices by reactive chlorine species (RCS) electrogenerated using Ti/IrO2 electrodes. Although this pollutant has been extensively treated by electrochemical techniques, little information is known about its degradation in fresh urine by electrogenerated RCS, and the understanding of its transformations using analyses of atomic charge. In this work, these two topics were discussed. Initially, the effect of current (10-40 mA) and supporting electrolyte (considering typical ions present in surface water and urine (Cl- and SO42-)) on the electrochemical system was evaluated. Then, the kinetics and primary transformations products involved in the elimination of ACE were described. It was found that, in distilled water, the process at 40 mA in NaCl presence led to 100 % of ACE degradation (10 min, 0.056 Ah L-1). Theoretical analyses of atomic charge for ACE indicated that the amide group is the most susceptible to attacks by RCS such as HOCl. On the other hand, degradation of acetaminophen in synthetic fresh urine was slower (21% of degradation after 60 min of treatment) than in distilled water. This was attributed to the other substances in the urine matrix, which induce competition for the degrading RCS.

Heterogeneous catalytic ozonation and peroxone-mediated removal of Acetaminophen using natural and modified hematite-rich soil, as efficient and environmentally friendly catalysts

Hormuz Red Soil (HRS), as a naturally hematite-containing mineral was used to enhance the catalytic ozonation process (COP) of Acetaminophen (ACT) elimination. The surface properties and particle size of HRS mainly composed of ɑ-Fe2O3 were modified via calcination (C-HRS) demonstrating notable catalytic activity. The catalytic activity of C-HRS was evaluated for the ozonation of ACT under various conditions. Complete degradation of 50 mg L−1 ACT was obtained within 10 min at natural conditions with 1.0 g L−1 of C-HRS which was > 10 times faster than single ozonation process (SOP). The C-HRS accelerated the decomposition of ozone to hydroxyl radical on the catalyst’s surface. Moreover, the C-HRS efficiently catalyzed the peroxone reaction for the degradation and mineralization of ACT. The C-HRS exhibited high stability and reusability in consecutive catalytic cycles. This work offers a new, effective, and low-cost catalyst for accelerating of ozone decomposition that can be used in oxidation of pollutants.

Sodium hydroxide-enhanced acetaminophen elimination in heat/peroxymonosulfate system: Production of singlet oxygen and hydroxyl radical

Owing to the high peroxide bond dissociation energy (377 kJ mol−1), peroxymonosulfate (PMS) is rather difficult to be activated by heat for degrading organic pollutants. This work is the first to add sodium hydroxide (NaOH) to enhance the elimination of acetaminophen in heat/PMS system. Heat/PMS system even possessed a better Performance than heat/peroxydisulfate (PDS) system with the addition of NaOH. Quenching experiments and electron paramagnetic resonance tests demonstrated that singlet oxygen and hydroxyl radical were the primary reactive oxygen species responsible for acetaminophen elimination in NaOH-enhanced heat/PMS system. Singlet oxygen mainly came from the alkaline activation of PMS, while hydroxyl radical was generated from the thermolysis of peroxide bond. Increasing PMS concentration and reaction temperature favored the production of reactive oxygen species and the elimination of acetaminophen. Nine degradation intermediates of acetaminophen were identified by LC/TOF/MS and the corresponding degradation pathways were proposed. Chloride ion significantly accelerated the elimination of acetaminophen, while humic acid and carbonate ion slightly retarded acetaminophen removal. NaOH-enhanced heat/PMS system was highly efficient in eliminating many organic pollutants and more prone to degrading electron-rich organics. This study developed a simple and efficient approach to strengthening the oxidation capacity of heat-activated PMS and highlighted the superiority of PMS to PDS in thermolysis under alkaline conditions.

Environmental protection by the adsorptive elimination of acetaminophen from water: A comprehensive review

Acetaminophen (ACT) is an effective and widely available analgesic and antipyretic used in medical practice. It can get into water from veterinary use, medical waste and pharmaceutical effluents. The aim of this review was to elaborate on the recent progress on ACT adsorption from water, present the findings in a structured written report and identify interesting new foundations for further work. ZnAl/biochar had the highest potential of removing ACT and can adsorb more than its weight of the pollutant (qmax > 1000 mg/g). The Langmuir and Freundlich isotherm models and the pseudo-second-order kinetics model were best-fits in most cases (usually at R2 > 0.99 threshold). It was observed that the key mechanisms of ACT uptake are π-π interactions, hydrogen bonds and electrostatic interaction. For most of the adsorbents, a >30% ACT removal efficiency was achievable after the 4 cycles. Effects as salting-out, electrostatic screening, and accumulation of moieties at sorbent-sorbate interfaces due to the competitive adsorption of ions and co-pollutants are profound in the uptake of ACT from aqueous solutions. Future perspectives were discussed in the area of process costing, adsorbent regeneration, mechanistic investigations and fixed-bed column adsorption.

Enhanced visible-light-driven photocatalytic degradation of acetaminophen over CeO2/I, K-codoped C3N4 heterojunction with tunable properties in simulated water matrix

• CeO 2 /IK-C 3 N 4 photocatalyst was synthesized for acetaminophen (ACT) photodegradation. • CeO 2 /IK-C 3 N 4 photocatalysts removed 98% ACT under visible light irradiation. • The photoactivity of CeO 2 /IK-C 3 N 4 is a function of pH, anions, CeO 2 amount and ACT concentration. • Active radicals including O 2 − and h + were identified and a type-II heterojunction mechanism was proposed. • CeO 2 /IK-C 3 N 4 showed excellent photocatalytic activity over ACT removal in three consecutive cycles. A novel visible-light-active photocatalyst consisting of CeO 2 nanoparticles and I, K-codoped graphitic carbon nitride (IK-C 3 N 4 ) was engineered using urea, potassium iodate and cerium nitrate as raw materials via a facile pyrolysis method. The CeO 2 /IK-C 3 N 4 composite was then applied for the rapid elimination of acetaminophen (ACT) under 465-nm visible light irradiation in aqueous solutions at different environmental parameters. The electronic images clearly showed that 5 – 20 nm CeO 2 can be tightly attached onto IK-C 3 N 4 . The charge imbalance of Ce element as well as oxygen vacancy of CeO 2 /IK-C 3 N 4 enhanced the photocatalytic activity of the composite. Moreover, the optical property and bandgap were easily tuned by changing the CeO 2 amounts. At optimum composition of 15 wt% CeO 2 , the bandgap of CeO 2 /IK-C 3 N 4 can narrow down to 2.38 eV. The photocatalytic activity of CeO 2 /IK-C 3 N 4 heterojunction toward ACT degradation is dependent on CeO 2 amounts and environmental parameters including pH, anions and initial ACT concentration. The calculated pseudo-first-order rate constants ranged from 0.039 to 0.051 min −1 . The radical species trapping experiments confirmed that O 2 − and h + play significant roles in ACT degradation. Thus, enhanced photodegradation of ACT is explained by type-II heterojunction mechanism. These findings provide a promising strategy of combining CeO 2 and doped g-C 3 N 4 for the effective removal of emerging pollutants under visible light irradiation, which can open a new route to synthesize novel heterojunction with high photoactivity for water purification and environmental sustainability.

Peroxymonosulfate activated with waste battery-based Mn-Fe oxides for pollutant removal: Electron transfer mechanism, selective oxidation and LFER analysis

Mn2O3-Fe2O3 catalyst was fabricated from spent alkaline batteries and used for effective elimination of acetaminophen (APAP) by activating peroxymonosulfate (PMS). APAP removal at various initial pH, its degradation pathway and the stability of catalyst were investigated. The Mn(III) was inferred to be the primary active site and Fe(III) could improve the corrosion resistance through intermetallic interactions. Chemical quenching experiments, electron paramagnetic resonance (EPR) spectroscopy, solvent exchange, open circuit potential (OCP) and chronoamperometry tests imply that APAP is oxidized by electron transfer through highly reactive surface-adsorbed PMS. Fourier transform infrared (FTIR), in situ Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) spectra and ionic strength experiments further revealed the interaction between the catalyst and PMS. The Mn2O3-Fe2O3/PMS system exhibits selective oxidation for different contaminants, and linear free energy relationship (LFER) was employed to investigate the effect of structure and properties of pollutant on the reaction kinetics. Pollutant with peak potential (Eop) > 0.91 V, the steady-state OCP in the Mn2O3-Fe2O3/PMS system, is resistant to oxidation; while pollutant with Eop < 0.91 V is prone to be oxidized and there is a good correlation between apparent first-order rate constant (k1) and Eop. The research not only puts in-depth study into PMS activation through environment-friendly Mn-Fe oxides from spent alkaline batteries, but also provides some new insights for nonradical mechanism, selective oxidation and LFER study.

Combined ozone oxidation process and adsorption methods for the removal of acetaminophen and amoxicillin from aqueous solution; kinetic and optimisation

Abstract The growing use of pharmaceuticals raises questions on their potential risk to human health and water quality. This research aimed to introduce a combined treatment technique with high performance in removing pharmaceutical micropollutants (MPs) from aqueous solution. The research included two steps, ozone treatment (first step) and adsorption technique (second step). The elimination of acetaminophen (ACT) and amoxicillin (AMX) with ozone reactor, first step, was optimised by artificial neural network (ANN). The optimisation process included two independent variables, namely, initial concentration of MPs and ozone dosage. On the basis of ANN, the linear regression coefficient denoted by R2 between predicted and experimental MP removals was close to 1. Result displayed that the prediction by the trained ANN is acceptable. Approximately 0.17 mg/L (84.8%) of ACT and 0.16 mg/L (82.7%) of AMX were removed at the initial concentration of 0.2 mg/L and ozone dosage of 15 mg/L. Beside it, ozonation experiments showed that the rate of constant (m − 1 s − 1 ) for ACT and AMX were 2.63 × 106 and 5.98 × 106 respectively. After treating by ozone reactor, water was subjected to pass through the cross-linked chitosan/bentonite as a fixed-bed column, for second step. ACT and AMX were not detected after step 2.

Effects of Beading Parameters for Development of Chitosan-Nano-Activated Carbon Biocomposite for Acetaminophen Elimination from Aqueous Sources

Abstract This article presents the development of a composite adsorbent based on chitosan (Cs) and nano-activated carbon (NAC). Potential application of Cs-NAC beads for acetaminophen (ACT) elimination from aqueous solution was also studied. In the present study, NAC coalesced with Cs to form composite adsorbents, which were obtained by using the extrusion-dripping technique. Effects of adsorbent preparation conditions were investigated. Results revealed that the best preparation parameters were as follows: (1) a Cs concentration of 1.75% (w/v) employing 70% (w/w) of NAC in the form of beads; (2) a dripping flowrate of 2 mL/min; and (3) a dripping distance of greater than 9 cm, to achieve 81% of ACT removal. Field emission scanning electron microscope, X-ray diffraction, Fourier transform infrared spectrometer, zeta potential, and Raman spectroscopy were used to determine the morphology of the prepared beads. Results revealed that the prepared adsorbents were able to remove ACT effectively. Encapsulating ...

Transcriptome association analysis identifies miR-375 as a major determinant of variable acetaminophen glucuronidation by human liver

Acetaminophen is the leading cause of acute liver failure (ALF) in many countries including the United States. Hepatic glucuronidation by UDP-glucuronosyltransferase (UGT) 1A subfamily enzymes is the major route of acetaminophen elimination. Reduced glucuronidation may predispose some individuals to acetaminophen-induced ALF, but mechanisms underlying reduced glucuronidation are poorly understood. We hypothesized that specific microRNAs (miRNAs) may reduce UGT1A activity by direct effects on the UGT1A 3′-UTR shared by all UGT1A enzyme transcripts, or by indirect effects on transcription factors regulating UGT1A expression. We performed an unbiased miRNA whole transcriptome association analysis using a bank of human livers with known acetaminophen glucuronidation activities. Of 754 miRNAs evaluated, 9 miRNAs were identified that were significantly overexpressed (p<0.05; >2-fold) in livers with low acetaminophen glucuronidation activities compared with those with high activities. miR-375 showed the highest difference (>10-fold), and was chosen for further mechanistic validation. We demonstrated using in silico analysis and luciferase reporter assays that miR-375 has a unique functional binding site in the 3′-UTR of the aryl hydrocarbon receptor (AhR) gene. Furthermore overexpression of miR-375 in LS180 cells demonstrated significant repression of endogenous AhR protein (by 40%) and mRNA (by 10%), as well as enzyme activity and/or mRNA of AhR regulated enzymes including UGT1A1, UGT1A6, and CYP1A2, without affecting UGT2B7, which is not regulated by AhR. Thus miR-375 is identified as a novel repressor of UGT1A-mediated hepatic acetaminophen glucuronidation through reduced AhR expression, which could predispose some individuals to increased risk for acetaminophen-induced ALF.

Massive acetaminophen overdose: effect of hemodialysis on acetaminophen and acetylcysteine kinetics

Context: Early onset acidosis from mitochondrial toxicity can be observed in massive acetaminophen poisoning prior to the development of hepatotoxicity. In this context, the efficacy of acetylcysteine to reverse mitochondrial toxicity remains unclear and hemodialysis may offer prompt correction of acidosis. Unfortunately, toxicokinetics of acetaminophen and acetylcysteine during extracorporeal treatments hemodialysis have seldom been described.Case details: An 18-year-old woman presented to the emergency department 60 minutes after ingestion of 100 g of acetaminophen, and unknown amounts of ibuprofen and ethanol. Initial assessment revealed an agitated patient. Her mental status worsened and she required intubation for airway protection. Investigations showed metabolic acidosis with lactate peaking at 8.6 mmol/L. Liver and coagulation profiles remained normal. Acetaminophen concentration peaked at 981 μg/ml (6496 μmol/L). Pending hemodialysis, the patient received 100 g of activated charcoal and an acetylcysteine infusion at 150 mg/kg over 1 hour, followed by 12.5 mg/kg/h for 4 hours. During hemodialysis, the infusion was maintained at 12.5 mg/kg/h to compensate for expected removal before it was decreased to 6.25 mg/kg for 20 hours after hemodialysis. The patient rapidly improved during hemodialysis and was discharged 48 hours post-admission.Toxicokinetics: The acetaminophen elimination half-life was 5.2 hours prior to hemodialysis, 1.9-hours during hemodialysis and 3.6 hours post hemodialysis. The acetaminophen and acetylcysteine clearances by A-V gradient during hemodialysis were 160.4 ml/min and 190.3 ml/min, respectively. Hemodialysis removed a total of 20.6 g of acetaminophen and 17.9 g of acetylcysteine.Conclusion: This study confirms the high dialyzability of both acetaminophen and acetylcysteine. Hemodialysis appears to be a beneficial therapeutic option in cases of massive acetaminophen ingestion with coma and lactic acidosis. Additionally, these results suggest that the infusion rate of acetylcysteine must be more than double during hemodialysis to compensate for its ongoing removal and provide similar plasma concentrations to the usual acetylcysteine regimen.

Hybrid bioreactor (HBR) of hollow fiber microfilter membrane and cross-linked laccase aggregates eliminate aromatic pharmaceuticals in wastewaters

Widespread detection of numerous micropollutants including aromatic pharmaceuticals in effluents of wastewater treatment plants has prompted much research aimed at efficiently eliminating these contaminants of environmental concerns. In the present work, a novel hybrid bioreactor (HBR) of cross-linked enzymes aggregates of laccase (CLEA-Lac) and polysulfone hollow fiber MF membrane was developed for the elimination of acetaminophen (ACT), mefenamic acid (MFA) and carbamazepine (CBZ) as model aromatic pharmaceuticals. The MF alone showed removals of the three drugs varying approximately from 50 to 90% over the course of 8h in the filtrate of aqueous solution. Synergistic action of the MF and CLEA-Lac during operation achieved eliminations from aqueous solution of around 99%, nearly 100% and up to 85% for ACT, MFA and CBZ, respectively. Under continuous operation, the HBR demonstrated elimination rates of the drugs from filtered wastewater up to 93% after 72h for CBZ and near complete elimination of ACT and MFA was achieved within 24h of treatment. Concomitantly to the drugs eliminations in the wastewater, the CLEA-Lac exhibited 25% residual activity while being continuously recycled with no activity in the filtrate. Meanwhile, the filtrate flowrate showed only minor decline indicating limited fouling of the membrane.

Acetaminophen elimination half-life in humans is unaffected by short-term consumption of sulfur amino acid-free diet.

Sulfation and glutathione (GSH) conjugation are important pathways for elimination of acetaminophen (APAP). Previous studies in rodents show that limitation of dietary sulfur amino acids (SAAs) reduces biosynthesis of 3'-phosphoadenosine-5'-phosphosulfate, the precursor for sulfation, and GSH, the precursor for the mercapturatic acid pathway. The amount of SAA needed for the metabolism of two doses of APAP is equivalent to 62% of the recommended dietary allowance (RDA) for SAA in humans. A decrease in the activity of these metabolic pathways could lead to decreased elimination of the reactive metabolite of APAP and possibly affect risk of APAP use. To determine whether intake of a SAA-deficient diet alters APAP metabolism, a pilot clinical study with a double-blind, cross-over design was performed. Subjects received the RDA for SAA for 3 days for equilibration. After admission to the clinical research unit, subjects were given a chemically defined diet with 100 or 0% of the RDA for SAA for 2 days. On day 3, two doses of APAP (15 mg/kg) or placebo were given successively within a 6-h interval. Plasma samples were collected at baseline and hourly for 12 h, and two 6-h urine aliquots were collected during this time course. The data show that SAA limitation 1) did not change the pattern of APAP metabolites in plasma or urine and 2) did not alter APAP pharmacokinetics. Thus, the results show that 2 days of diet completely devoid of SAA have no effect on APAP metabolism or disposition in healthy humans.