Xenobiotics Research Articles

P-glycoprotein activity in vivo in older adults: physiological, -pathophysiological and pharmacokinetic interplay at the blood-brain barrier

p-glycoprotein (P-gp) is an efflux transporter of xenobiotic and endogenous compounds across the blood-brain barrier (BBB). P-gp plays an essential role by limiting passage of these compounds into the brain tissue. It is susceptible to drug-drug interactions when interactors drugs are co-administrated. The efficiency of P-gp may be affected by the aging process and the development of neurodegenerative diseases. Studying this protein in older adults is therefore highly relevant for all these reasons. Understanding P-gp activity in vivo is essential when considering the physiological, pathophysiological, and pharmacokinetic perspectives, as these aspects seem to be interconnected to some extent. In vivo exploration in humans is based on neuroimaging techniques, which have been improving over the last years. The advancement of exploration and diagnostic tools is opening up new prospects for understanding P-gp activity at the BBB.

Integrated omics of Saccharomyces cerevisiae CENPK2-1C reveals pleiotropic drug resistance and lipidomic adaptations to cannabidiol

Yeast metabolism can be engineered to produce xenobiotic compounds, such as cannabinoids, the principal isoprenoids of the plant Cannabis sativa, through heterologous metabolic pathways. However, yeast cell factories continue to have low cannabinoid production. This study employed an integrated omics approach to investigate the physiological effects of cannabidiol on S. cerevisiae CENPK2-1C yeast cultures. We treated the experimental group with 0.5 mM CBD and monitored CENPK2-1C cultures. We observed a latent-stationary phase post-diauxic shift in the experimental group and harvested samples in the inflection point of this growth phase for transcriptomic and metabolomic analysis. We compared the transcriptomes of the CBD-treated yeast and the positive control, identifying eight significantly overexpressed genes with a log fold change of at least 1.5 and a significant adjusted p-value. Three notable genes were PDR5 (an ABC-steroid and cation transporter), CIS1, and YGR035C. These genes are all regulated by pleiotropic drug resistance linked promoters. Knockout and rescue of PDR5 showed that it is a causal factor in the post-diauxic shift phenotype. Metabolomic analysis revealed 48 significant spectra associated with CBD-fed cell pellets, 20 of which were identifiable as non-CBD compounds, including fatty acids, glycerophospholipids, and phosphate-salvage indicators. Our results suggest that mitochondrial regulation and lipidomic remodeling play a role in yeast’s response to CBD, which are employed in tandem with pleiotropic drug resistance (PDR). We conclude that bioengineers should account for off-target product C-flux, energy use from ABC-transport, and post-stationary phase cell growth when developing cannabinoid-biosynthetic yeast strains.

Tissue-, Region-, and Gene-Specific Induction of Microsomal Epoxide Hydrolase Expression and Activity in the Mouse Intestine by Arsenic in Drinking Water.

This study aimed to characterize the effects of arsenic exposure on the expression of microsomal epoxide hydrolase (mEH or EPHX1) and soluble epoxide hydrolase (sEH or EPHX2) in the liver and small intestine. C57BL/6 mice were exposed to sodium arsenite in drinking water at various doses for up to 28 days. Intestinal, but not hepatic, mEH mRNA and protein expression was induced by arsenic at 25 ppm, in both males and females, whereas hepatic mEH expression was induced by arsenic at 50 or 100 ppm. The induction of mEH was gene specific, as the arsenic exposure did not induce sEH expression in either tissue. Within the small intestine, mEH expression was induced only in the proximal, but not the distal segments. The induction of intestinal mEH was accompanied by increases in microsomal enzymatic activities toward a model mEH substrate, cis-stilbene oxide, and an epoxide-containing drug, oprozomib, in vitro, and by increases in the levels of PR-176, the main hydrolysis metabolite of oprozomib, in the proximal small intestine of oprozomib-treated mice. These findings suggest that intestinal mEH, playing a major role in converting xenobiotic epoxides to less reactive diols, but not sEH, preferring endogenous epoxides as substrates, is relevant to the adverse effects of arsenic exposure, and that further studies of the interactions between drinking water arsenic exposure and the disposition or possible adverse effects of epoxide-containing drugs and other xenobiotic compounds in the intestine are warranted. SIGNIFICANCE STATEMENT: Consumption of arsenic-contaminated water has been associated with increased risks of various adverse health effects, such as diabetes, in humans. The small intestinal epithelial cells are the main site of absorption of ingested arsenic, but they are not well characterized for arsenic exposure-related changes. This study identified gene expression changes in the small intestine that may be mechanistically linked to the adverse effects of arsenic exposure and possible interactions between arsenic ingestion and the pharmacokinetics of epoxide-containing drugs in vivo.

Evaluation of Apis mellifera brain morphophysiology in response to titanium dioxide nanoparticles and deltamethrin co‐exposure

AbstractHoneybees are important insects, both economically and as pollinators. While foraging, bees can come in contact with environmental pollutants such as pesticides, possibly in combination with other xenobiotic compounds that may compromise bee health. Our current study investigated the acute exposure to nanosized titanium dioxide, a common additive in food, cosmetics, paints and agricultural products, along with deltamethrin (DLT), a well‐known pyrethroid pesticide. The effects of binary exposure to titanium dioxide nanoparticles (TiO2‐NPs) nanoparticles at concentrations of 25, 50, 75 and 100 μg/mL with DLT were noted on Apis mellifera brain histology along with their possible synergism. In DLT‐ and combined TiO2‐NP‐DLT treated bees, survival rates were lowered and several histological alterations were observed including an increased number of cells with pyknotic nuclei, along with cytoplasmic vacuolization, chromatin compaction and degeneration indicating autophagic activity and a decrease in the cross‐sectional area of nanoparticle‐treated mushroom body calyces. A synergistic relationship between TiO2‐NPs and DLT was revealed, while LD50 for combined TiO2‐NP‐DLT treatment was 0.101, 0.09 and 0.02 μg/bee at 24, 48 and 72 h, respectively. In summary, results demonstrate that TiO2‐NP and DLT co‐exposure can induce damage in bee brain structures at higher concentrations, which indicates an additional risk factor for bee health in the field.

Generation and characterization of cytochrome P450 3A74 CRISPR/Cas9 knockout bovine foetal hepatocyte cell line (BFH12)

In human, the cytochrome P450 3A (CYP3A) subfamily of drug-metabolizing enzymes (DMEs) is responsible for a significant number of phase I reactions, with the CYP3A4 isoform superintending the hepatic and intestinal metabolism of diverse endobiotic and xenobiotic compounds. The CYP3A4-dependent bioactivation of chemicals may result in hepatotoxicity and trigger carcinogenesis. In cattle, four CYP3A genes (CYP3A74, CYP3A76, CYP3A28 and CYP3A24) have been identified. Despite cattle being daily exposed to xenobiotics (e.g., mycotoxins, food additives, drugs and pesticides), the existing knowledge about the contribution of CYP3A in bovine hepatic metabolism is still incomplete. Nowadays, CRISPR/Cas9 mediated knockout (KO) is a valuable method to generate in vivo and in vitro models for studying the metabolism of xenobiotics. In the present study, we successfully performed CRISPR/Cas9-mediated KO of bovine CYP3A74, human CYP3A4-like, in a bovine foetal hepatocyte cell line (BFH12). After clonal expansion and selection, CYP3A74 ablation was confirmed at the DNA, mRNA, and protein level. The subsequent characterization of the CYP3A74 KO clone highlighted significant transcriptomic changes (RNA-sequencing) associated with the regulation of cell cycle and proliferation, immune and inflammatory response, as well as metabolic processes. Overall, this study successfully developed a new CYP3A74 KO in vitro model by using CRISPR/Cas9 technology, which represents a novel resource for xenobiotic metabolism studies in cattle. Furthermore, the transcriptomic analysis suggests a key role of CYP3A74 in bovine hepatocyte cell cycle regulation and metabolic homeostasis.

Deorphanizing solute carriers in Saccharomyces cerevisiae for secondary uptake of xenobiotic compounds.

The exchange of small molecules between the cell and the environment happens through transporter proteins. Besides nutrients and native metabolic products, xenobiotic molecules are also transported, however it is not well understood which transporters are involved. In this study, by combining exo-metabolome screening in yeast with transporter characterization in Xenopus oocytes, we mapped the activity of 30 yeast transporters toward six small non-toxic substrates. Firstly, using LC-MS, we determined 385 compounds from a chemical library that were imported and exported by S. cerevisiae. Of the 385 compounds transported by yeast, we selected six compounds (viz. sn-glycero-3-phosphocholine, 2,5-furandicarboxylic acid, 2-methylpyrazine, cefadroxil, acrylic acid, 2-benzoxazolol) for characterization against 30 S. cerevisiae xenobiotic transport proteins expressed in Xenopus oocytes. The compounds were selected to represent a diverse set of chemicals with a broad interest in applied microbiology. Twenty transporters showed activity toward one or more of the compounds. The tested transporter proteins were mostly promiscuous in equilibrative transport (i.e., facilitated diffusion). The compounds 2,5-furandicarboxylic acid, 2-methylpyrazine, cefadroxil, and sn-glycero-3-phosphocholine were transported equilibratively by transporters that could transport up to three of the compounds. In contrast, the compounds acrylic acid and 2-benzoxazolol, were strictly transported by dedicated transporters. The prevalence of promiscuous equilibrative transporters of non-native substrates has significant implications for strain development in biotechnology and offers an explanation as to why transporter engineering has been a challenge in metabolic engineering. The method described here can be generally applied to study the transport of other small non-toxic molecules. The yeast transporter library is available at AddGene (ID 79999).

Endoplasmic Reticulum Stress in Gliomas: Exploiting a Dual-Effect Dysfunction through Chemical Pharmaceutical Compounds and Natural Derivatives for Therapeutical Uses.

The endoplasmic reticulum maintains proteostasis, which can be disrupted by oxidative stress, nutrient deprivation, hypoxia, lack of ATP, and toxicity caused by xenobiotic compounds, all of which can result in the accumulation of misfolded proteins. These stressors activate the unfolded protein response (UPR), which aims to restore proteostasis and avoid cell death. However, endoplasmic response-associated degradation (ERAD) is sometimes triggered to degrade the misfolded and unassembled proteins instead. If stress persists, cells activate three sensors: PERK, IRE-1, and ATF6. Glioma cells can use these sensors to remain unresponsive to chemotherapeutic treatments. In such cases, the activation of ATF4 via PERK and some proteins via IRE-1 can promote several types of cell death. The search for new antitumor compounds that can successfully and directly induce an endoplasmic reticulum stress response ranges from ligands to oxygen-dependent metabolic pathways in the cell capable of activating cell death pathways. Herein, we discuss the importance of the ER stress mechanism in glioma and likely therapeutic targets within the UPR pathway, as well as chemicals, pharmaceutical compounds, and natural derivatives of potential use against gliomas.

Cryo-EM structure of P-glycoprotein bound to triple elacridar inhibitor molecules

P-glycoprotein (P-gp) is an ATP-binding cassette transporter known for its roles in expelling xenobiotic compounds from cells and contributing to cellular drug resistance through multidrug efflux. This mechanism is particularly problematic in cancer cells, where it diminishes the therapeutic efficacy of anticancer drugs. P-gp inhibitors, such as elacridar, have been developed to circumvent the decrease in drug efficacy due to P-gp efflux. An earlier study reported the cryo-EM structure of human P-gp-Fab (MRK-16) complex bound by two elacridar molecules, at a resolution of 3.6 Å. In this study, we have obtained a higher resolution (2.5 Å) structure of the P-gp- Fab (UIC2) complex bound by three elacridar molecules. This finding, which exposes a larger space for compound-binding sites than previously acknowledged, has significant implications for the development of more selective inhibitors and enhances our understanding of the compound recognition mechanism of P-gp.

Revealing the comprehensive impact of organic compounds on the partial nitrification-anammox system during incineration leachate treatment: metabolic hierarchy and adaptation

Organics, as widespread pollutants in high-strength ammonia wastewater, typically exert adverse effects on the performance of partial nitrification-anammox (PNA) systems. However, the in-depth knowledge on how microbial consortia respond to these disturbances remains limited. In this study, we unveiled the evolution of complex organic matter flow and its impact on the metabolic hierarchy and adaptation of microbial consortia, employing multi-omics approaches, i.e., 16S amplicon sequencing, metagenomics, and metabolomics. In a two-stage PNA system sequentially treating synthetic wastewater and incineration leachate over 230 days, partial nitrification stayed stable (nitrite accumulation > 97%) while anammox efficiency dropped (nitrogen removal decreased from 86% to 78%). The phenomenon was revealed to be correlated with the evolution of dissolved organic matter (DOM) and xenobiotic organic compounds (XOCs). In the PN stage, ammonia-oxidizing bacteria (AOB) exhibited excellent adaptability through active metabolic regulation after treating leachate. Numerous heterotrophs proliferated to utilize DOM and XOCs, triggering a “boom” state evident in the glycerophospholipid metabolism. However, in the anammox stage, the competition between carbon fixation and central carbon metabolism within autotrophs and heterotrophs became evident. Increased biosynthesis costs inhibited the central metabolism (specific anammox activity decreased by 66%) and the Wood-Ljungdahl pathway of anammox bacteria (AnAOB) in the presence of recalcitrant organics. Additionally, the degradation of organics was limited, exhibiting a “bust” state. This study revealed the metabolic adaption and susceptibility of AOB and AnAOB in response to organics from the leachate, demonstrating the applicability of the two-stage configuration for treating high-strength wastewater containing abundant and diverse organics.

Modulation of the Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2) by Xenobiotic Compounds and Its Relevance to Human Diseases.

Mast cells (MCs) are immune cells that reside in tissues; particularly in the skin, and in the gastrointestinal and respiratory tracts. In recent years, there has been considerable interest in the Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2), which is present on the surface of MCs and can be targeted by multiple exogenous and endogenous ligands. It is potentially implicated in non-IgE-mediated pseudoallergic reactions and inflammatory conditions such as asthma or atopic dermatitis. In this paper, we review natural products and herbal medicines that may potentially interact with MRGPRX2. They mainly belong to the classes of polyphenols, flavonoids, coumarins, and alkaloids. Representative compounds include rosmarinic acid, liquiritin from licorice extract, osthole, and sinomenine, respectively. While evidence-based medicine studies are still required, these compounds have shown diverse effects, such as antioxidant, analgesic, anti-inflammatory, or neuroprotective. However, despite potential beneficial effects, their use is also burdened with risks of fatal reactions such as anaphylaxis. The role of MRGPRX2 in these reactions is a subject of debate. This review explores the literature on xenobiotic compounds from herbal medicines that have been shown to act as MRGPRX2 ligands, and their potential clinical significance.

Kırmızı Reishi Mantarı (Ganoderma lucidum) Extratının Karbon Tetraklorür ile İndüklenen Karaciğer Hasarı ve Siklooksijenaz-2 İmmunoreaktivitesi Üzerine Etkisi

Carbon tetrachloride (CCl4) is a xenobiotic compound with toxicological action. It is absorbed by gastrointestinal system, respiratory system, and skin. Studies have reported that many countries have used Ganoderma lucidum (GL, Reishi Mushroom) as a medicinal mushroom against liver diseases induced by hepatotoxic agents such as CCl4 for more than thousands of years and is used for many diseases, including cancer since it has been thought that it increases resistance against them and treats them. In the present study, immunohistochemical localization and expression of cyclooxygenase-2 (COX-2) by administrating carbon tetrachloride and Ganoderma lucidum in adult rats were examined. In the study, 32 adult Spraque-Dawley male rats that were 8-10 weeks old were used. Rats were divided into 4 groups as control, CCI4, Ganoderma lucidum (GL), and CCI4+GL. As a result of the experimental applications, the liver tissue was found to be normal in the control and GL groups, and multifocal necrosis areas, hepatocellular degeneration, cell infiltration, sinusoidal dilatation, and congestion were observed in the central and portal areas in CCI4 group. In the CCI4+GL group, decreases were observed in lesion severity and density. COX-2 immunoreactivity was detected as more common in hepatocyte cytoplasm in the area from the central vena to the Kiernan space, while it was observed as sporadic in the hepatocyte nucleus. While CCI4 caused a decrease in total antioxidant level (TAS) in blood plasma samples, it caused an increase in total oxidant level (TOS), Aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels. It is seen that Ganoderma lucidum, which has an important place in alternative and folk medicine, reduces oxidative stress with its hepatoprotective effect and inhibits the inflammatory response in the liver.

White Rot Fungi as Tools for the Bioremediation of Xenobiotics: A Review.

Industrial development has enhanced the release into the environment of large quantities of chemical compounds with high toxicity and limited prospects of degradation. The pollution of soil and water with xenobiotic chemicals has become a major ecological issue; therefore, innovative treatment technologies need to be explored. Fungal bioremediation is a promising technology exploiting their metabolic potential to remove or lower the concentrations of xenobiotics. In particular, white rot fungi (WRF) are unique microorganisms that show high capacities to degrade a wide range of toxic xenobiotic compounds such as synthetic dyes, chlorophenols, polychlorinated biphenyls, organophosphate pesticides, explosives and polycyclic aromatic hydrocarbons (PAHs). In this review, we address the main classes of enzymes involved in the fungal degradation of organic pollutants, the main mechanisms used by fungi to degrade these chemicals and the suitability of fungal biomass or extracellular enzymes for bioremediation. We also exemplify the role of several fungi in degrading pollutants such as synthetic dyes, PAHs and emerging pollutants such as pharmaceuticals and perfluoroalkyl/polyfluoroalkyl substances (PFASs). Finally, we discuss the existing current limitations of using WRF for the bioremediation of polluted environments and future strategies to improve biodegradation processes.

Recent advances in eco-friendly technology for decontamination of pulp and paper mill industrial effluent: a review.

The economic development of a country directly depends upon industries. But this economic development should not be at the cost of our natural environment. A substantial amount of water is spent during paper production, creating water scarcity and generating wastewater. Therefore, the Pollution Control Board classifies this industry into red category. Water is used in different papermaking stages such as debarking, pulping or bleaching, washing, and finishing. The wastewater thus generated contains lignin and xenobiotic compounds such as resin acids, chlorinated lignin, phenols, furans, dioxins, chlorophenols, adsorbable organic halogens (AOX), extractable organic halogens (EOCs), polychlorinated biphenyls, plasticizers, and polychlorinated dibenzodioxins. Nowadays, several microorganisms are used in the detoxification of these hazardous effluents. Researchers have found that microbial degradation is the most promising treatment method to remove high biological oxygen demand (BOD) and chemical oxygen demand (COD) from wastewater. Microorganisms also remove AOX toxicity, chlorinated compounds, suspended solids, color, lignin, derivatives, etc. from the pulp and paper mill effluents. But in the current scenario, mill effluents are known to deteriorate the environment and therefore it is highly desirable to deploy advanced technologies for effluent treatment. This review summarizes the eco-friendly advanced treatment technologies for effluents generated from pulp and paper mills.

Metabolism of Xenobiotic Compounds Increases Free Radical Production and Reduces Endogenous Antioxidant Mechanisms

Xenobiotic compounds are foreign substances that enter the body. These substances include drugs, insecticides, toluene, chloroform, formalin, and others that can enter by inhalation, through skin exposure or swallowed together with food. The use of xenobiotic compounds is increasing every year along with the development of the industrial sector, which impacts greater exposure for workers. Xenobiotic compounds that enter the body will cause harm to the body, and they will be detoxified in the liver. Xenobiotic compounds can bind to cytochrome p450 isoform 2E1, which will cause the formation of free radicals. A body exposed to xenobiotic compounds can respond by reducing free radicals using endogenous antioxidants. They are Superoxide Dismutase (SOD) and Glutathione Peroxidase (GPX). If the amount of free radicals exposure is too large, oxidative stress will occur. It triggers liver cell damage and release of alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST) into the blood vessels, which causes an increase in these enzymes in the blood.

A Preliminary Investigation into the Degradation of Asbestos Fibres in Soils, Rocks and Building Materials Associated with Naturally Occurring Biofilms

Bioremediation utilizes living organisms such as plants, microbes and their enzymatic products to reduce toxicity in xenobiotic compounds. Microbial-mediated bioremediation is cost effective and sustainable and in situ application is easily implemented. Either naturally occurring metabolic activity can be utilized during bioremediation for the degradation, transformation or accumulation of substances, or microbial augmentation with non-native species can be exploited. Despite the perceived low potential for the biological degradation of some recalcitrant compounds, successful steps towards bioremediation have been made, including with asbestos minerals, which are prevalent in building stock (created prior to the year 2000) in New Zealand. Evidence of the in situ biodegradation of asbestos fibres was investigated in samples taken from a retired asbestos mine, asbestos-contaminated soils and biofilm or lichen-covered asbestos-containing building materials. Microbial diversity within the biofilms to be associated with the asbestos-containing samples was investigated using internal transcribed spacer and 16S DNA amplicon sequencing, supplemented with isolation and culturing on agar plates. A range of fungal and bacterial species were found, including some known to produce siderophores. Changes to fibre structure and morphology were analysed using Transmission Electron Microscopy and Energy-Dispersive X-ray Spectroscopy. Chrysotile fibrils from asbestos-containing material (ACMs), asbestos-containing soils, and asbestos incorporated into lichen material showed signs of amorphisation and dissolution across their length, which could be related to biological activity.

Overview of Soil Xenobiotics and their Biological Remediation Strategies

Xenobiotic pollution of the environment is a global phenomenon brought on by human activity as a result of increased urbanisation and population expansion. Pesticides, petrol, solvents, alkanes, polycyclic hydrocarbons (PAHs), antibiotics, artificial azo dyes, pollutants (polychlorinated biphenyls and dioxins), and polyaromatic, chlorinated, and nitroaromatic substances are examples of xenobiotics. Xenobiotics are primarily defined as substances that are foreign to a living thing and have an inclination to collect in the environment,where they can be harmful for existing ecosystem. The natural environment is impacted in a number of ways, both short- and long-term, when these dangerous contaminants are released. The scientific study of xenobiotic compound biodegradation—which uses microorganisms' catabolic powers to break down poisonous and hazardous xenobiotics—has received a lot of attention in the last few decades. Numerous bacteria possessing remarkable capacity for biodegrading xenobiotic substances have been identified, and their novel degradation routes have been clarified. The field of molecular approach to biodegradation research is fairly young. Therefore, in order to create efficient and environmentally beneficial "green" technology, it is imperative to investigate the microbial biodiversity.

Facultative endosymbionts modulate the aphid reproductive performance on wheat cultivars differing in contents of benzoxazinoids.

Facultative bacterial endosymbionts have the potential to influence the interactions between aphids, their natural enemies, and host plants. Among the facultative symbionts found in populations of the grain aphid Sitobion avenae in central Chile, the bacterium Regiella insecticola is the most prevalent. In this study, we aimed to investigate whether infected and cured aphid lineages exhibit differential responses to wheat cultivars containing varying levels of the benzoxazinoid DIMBOA (2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one), which is a xenobiotic compound produced by plants. Specifically, we examined the reproductive performance responses of the most frequently encountered genotypes of Sitobion avenae when reared on wheat seedlings expressing low, medium, and high concentrations of DIMBOA. Our findings reveal that the intrinsic rate of population increase (rm ) in cured lineages of Sitobion avenae genotypes exhibits a biphasic pattern, characterized by the lowest rm and an extended time to first reproduction on wheat seedlings with medium levels of DIMBOA. In contrast, the aphid genotypes harbouring Regiella insecticola display idiosyncratic responses, with the two most prevalent genotypes demonstrating improved performance on seedlings featuring an intermediate content of DIMBOA compared to their cured counterparts. This study represents the first investigation into the mediating impact of facultative endosymbionts on aphid performance in plants exhibiting varying DIMBOA contents. These findings present exciting prospects for identifying novel targets for aphid control by manipulating the presence of aphid symbionts. © 2023 Society of Chemical Industry.

Flubendazole carbonyl reduction in drug-susceptible and drug-resistant strains of the parasitic nematode Haemonchus contortus: changes during the life cycle and possible inhibition

Carbonyl-reducing enzymes (CREs) catalyse the reduction of carbonyl groups in many eobiotic and xenobiotic compounds in all organisms, including helminths. Previous studies have shown the important roles of CREs in the deactivation of several anthelmintic drugs (e.g., flubendazole and mebendazole) in adults infected with the parasitic nematode Haemonchus contortus, in which the activity of a CRE is increased in drug-resistant strains. The aim of the present study was to compare the abilities of nematodes of both a drug-susceptible strain (ISE) and a drug-resistant strain (IRE) to reduce the carbonyl group of flubendazole (FLU) in different developmental stages (eggs, L1/2 larvae, L3 larvae, and adults). In addition, the effects of selected CRE inhibitors (e.g., glycyrrhetinic acid, naringenin, silybin, luteolin, glyceraldehyde, and menadione) on the reduction of FLU were evaluated in vitro and ex vivo in H. contortus adults. The results showed that FLU was reduced by H. contortus in all developmental stages, with adult IRE females being the most metabolically active. Larvae (L1/2 and L3) and adult females of the IRE strain reduced FLU more effectively than those of the ISE strain. Data from the in vitro inhibition study (performed with cytosolic-like fractions of H. contortus adult homogenate) revealed that glycyrrhetinic acid, naringenin, mebendazole and menadione are effective inhibitors of FLU reduction. Ex vivo study data showed that menadione inhibited FLU reduction and also decreased the viability of H. contortus adults to a similar extent. Naringenin and mebendazole were not toxic at the concentrations tested, but they did not inhibit the reduction of FLU in adult worms ex vivo.

Xenobiotic Removal by Trametes hirsuta LE-BIN 072 Activated Carbon-Based Mycelial Pellets: Remazol Brilliant Blue R Case Study

As a toxic xenobiotic compound, the anthraquinone dye Remazol Brilliant Blue R (RBBR) poses a serious threat to aquatic ecosystems. In the present study, the ability of Trametes hirsuta to remove RBBR from the medium was investigated, and the role of adsorption by fungal mycelium and biodegradation by fungal enzymes was evaluated. It was shown that the whole fungal culture was able to remove up to 97% of the dye within the first four hours of incubation. Based on enzymatic activities in the culture broth, laccases were proposed to be the main enzymes contributing to RBBR degradation, and RT-qPCR measurements demonstrated an increase in transcription for the two laccase genes—lacA and lacB. Composite mycelial pellets of T. hirsuta with improved adsorption ability were prepared by adding activated carbon to the growth medium, and the induction of laccase activity by carbon was shown. For composite pellets, the RBBR decolorization degree was about 1.9 times higher at 1 h of incubation compared to carbon-free pellets. Hence, it was shown that using fungal mycelium pellets containing activated carbon can be an effective and economical method of dye removal.

UV light assisted degradation of acid orange azo dye by ZVI-ZnS and effluent toxicity effects

Azo dyes, the most common synthetic dyes used in the textile industry, are known xenobiotic compounds and recalcitrant to conventional degradation treatments. As consequence, such contaminants are often discharged into the effluents, treating aquatic ecosystems. Among several processes, the use of zero valent iron (ZVI) represents a suitable alternative to degrade organic molecules containing azo bonds. However, its applications are limited by corrosion and loss of reactivity over the time. To overcome these constraints, ZVI has been coupled to a suitable semiconductor (ZnS) to get a catalytic composite (ZVI-ZnS) active under UV light. The present work deals with the degradation of acid orange (AO7), used as model azo dye, by UV/ZVI-ZnS, as one step treatment and in combination with an adsorption process by biochar. The influence of ZVI-ZnS concentration (0.25, 0.5, 1 and 2 g/L) and reaction time (0–160 min) on degradation of AO7 were investigated. Intermediates formation was monitored by ESI-FT-ICR-MS analysis and the effluent toxicity was assessed by using Artemia franciscana. The experimental results showed that the UV/ZVI-ZnS process at 1 g/L of catalyst allowed to achieve a removal of AO7 up to 97% after 10 min. An increase of the dye relative concentrations as well as the toxicity related to intermediates formations has been observed for treatment time higher than 10 min. The total removal of AO7 together with effluent toxicity reduction was obtained only after the combined treatment (UV/ZVI-ZnS + biochar).