Journal of Xenobiotics

COVID-19, occurring due to SARS-COV-2 infection, is the most recent pandemic disease that has led to three million deaths at the time of writing. A great deal of effort has been directed towards altering the virus trajectory and/or managing the interactions of the virus with its subsequent targets in the human body; these interactions can lead to a chain reaction-like state manifested by a cytokine storm and progress to multiple organ failure. During cytokine storms the ratio of pro-inflammatory to anti-inflammatory mediators is generally increased, which contributes to the instigation of hyper-inflammation and confers advantages to the virus. Because cytokine expression patterns fluctuate from one person to another and even within the same person from one time to another, we suggest a road map of COVID-19 management using an individual approach instead of focusing on the blockbuster process (one treatment for most people, if not all). Here, we highlight the biology of the virus, study the interaction between the virus and humans, and present potential pharmacological and non-pharmacological modulators that might contribute to the global war against SARS-COV-2. We suggest an algorithmic roadmap to manage COVID-19. Full article

The occurrence of pharmaceuticals in the environment is an everyday recognized concern worldwide, and drugs as environmental contaminants have been detected in water and soil systems, posing risks to humans and wildlife. The presence of drugs in wastewater, groundwater, and even drinking water occurs in several countries, including Brazil, where the pharmaceutical market is expanding over the years. The adverse, harmful effects of pharmaceuticals in the environment range from the spreading of antimicrobial resistance and species survival to the interference with reproduction and increased cancer incidence in humans. Therefore, it is demanding to count on proper legislation to prevent these pollutants from entering the distinct environment compartments. In some developed countries, laws, directives, programs, and initiatives regarding drug disposal reach a mature status. In Brazil, federal laws dealing with drug residues’ management are recent, with flaws that might facilitate non-compliance with drug pollution issues. Besides, pharmacies and drugstores are not obligated to collect unneeded household medicines, while particular State laws aim to ordinate the disposal of drug residues regionally. In this review, we consider the current knowledge about pharmaceutical (drug) pollution, the recommendation and regulations on the disposal of useless medicines in some countries, and in the context of the expanding pharmaceutical market in Brazil. The awareness of emerging contaminants in the environment, besides the joint effort of authorities, consumers, and the general public nationwide, will be required to avoid pharmaceutical/drug pollution and achieve an eco-friendly environment and a sustainable society. Full article

Blue mussels, Mytilus edulis, inhabiting tidal zones, are naturally exposed to fluctuating environmental conditions (e.g., fluctuations in temperature and salinities), while horse mussels, Modiolus modiolus, live under relatively invariable shelf water conditions. The present investigation tested the hypothesis: blue mussels, in comparison to horse mussels, have an increased ability to tolerate the stress of pollution combined with low salinity. To assess the response of blue mussels and horse mussels to oil pollution at seawater salinities of 25 psu (normal) and 15 psu (low), we used a combination of heart rate and lipid composition as physiological and biochemical indicators, respectively. A sharp decrease in heart rate as well as important fluctuations in cardiac activity was observed under all oil concentrations. Modifications in the concentrations of the main membrane lipid classes (phosphatidylcholine, phosphatidylethanolamine, and cholesterol) and storage lipids (primarily triacylglycerols) in response to different crude oil concentrations were time- and dose-dependent. Both chosen indicators showed a high sensitivity to crude oil contamination. Furthermore, both bivalve species showed similar responses to oil pollution, suggesting a universal mechanism for biochemical adaptation to crude oil pollution. Full article

Benthic dinoflagellates produce a wide array of bioactive compounds, primarily polyketides, that cause toxic effects on human consumers of seafood and perhaps mediate species interactions in the benthic microenvironment. This study assesses toxic and other bioactive effects of the benthic dinoflagellate Amphidinium operculatum (strain AA60) in two targeted bioassays. The brine shrimp (Artemia salina) bioassay revealed lethal effects of direct exposure to live dinoflagellate cells (Treatment A) and even higher potency with ethanolic extracts of lysed cells (Treatment D). There were no inimical bioactive effects of components released to the aqueous growth medium (Treatment B) or from aqueous cell lysates (Treatment C). The hypothesis that released bioactive compounds provide a chemical defense against metazoan grazers is therefore not supported by these results. The cytotoxic effect of ethanolic crude extracts of this dinoflagellate exhibited mild to high growth reduction effects on six human cancer cell lines. In particular, crude cell-free extracts proved highly growth-inhibitory activity towards breast and lung cancer cell lines MCF-7 and SKLU-1, respectively. Preliminary anti-cancer results indicate that natural bioactive compounds from Amphidinium are worthy of structural characterization and further toxicological investigation as potential therapeutants. Full article

Prostate cancer is one of the most common cancers diagnosed in men in the United States and the second leading cause of cancer-related deaths worldwide. Since over 60% of prostate cancer cases occur in men over 65 years of age, and this population will increase steadily in the coming years, prostate cancer will be a major cancer-related burden in the foreseeable future. Accumulating data from more recent research suggest that the tumor microenvironment (TME) plays a previously unrecognized role in every stage of cancer development, including initiation, proliferation, and metastasis. Prostate cancer is not only diagnosed in the late stages of life, but also progresses relatively slowly. This makes prostate cancer an ideal model system for exploring the potential of natural products as cancer prevention and/or treatment reagents because they usually act relatively slowly compared to most synthetic drugs. Resveratrol (RSV) is a naturally occurring stilbenoid and possesses strong anti-cancer properties with few adverse effects. Accumulating data from both in vitro and in vivo experiments indicate that RSV can interfere with prostate cancer initiation and progression by targeting the TME. Therefore, this review is aimed to summarize the recent advancement in RSV-inhibited prostate cancer initiation, proliferation, and metastasis as well as the underlying molecular mechanisms, with particular emphasis on the effect of RSV on TME. This will not only better our understanding of prostate cancer TMEs, but also pave the way for the development of RSV as a potential reagent for prostate cancer prevention and/or therapy. Full article

The recent advances of novel methodologies such as non-targeted and suspect screening based on high-resolution mass spectrometry (HRMS) have paved the way to a new paradigm for exposure assessment. These methodologies allow to profile simultaneously thousands of small unknown molecules present in environmental and biological samples, and therefore hold great promises in order to identify more efficiently hazardous contaminants potentially associated with increased risks of developing adverse health outcomes. In order to further explore the potential of these methodologies and push the transition from research applications towards regulatory purposes, robust harmonized quality standards have to be implemented. Here, we discuss the feasibility of using ISO/IEC 17025: 2017 as a guideline to implement non-targeted and suspect screening methodologies in laboratories, whether it is for accreditation purposes or not. More specifically, we identified and then discussed how specificities of non-targeted HRMS methodology can be accounted for in order to comply with the specific items of ISO/IEC 17025: 2017. We also discussed other specificities of HRMS methodologies (e.g., need for digital storage capacity) that are so far not included in the ISO/IEC 17025 requirements but should be considered. This works aims to fuel and expand the discussion in order to subsidize new opportunities of harmonization for non-targeted and suspect screening. Full article

The objective of this study was to develop an integrative approach in ecotoxicology (from biomarkers to population genetics) to assess the ecological status of fish populations. Flounders (Platichthys flesus) collected after the spawning season in the heavily polluted Seine estuary were compared with the moderately polluted Bay of Douarnenez. The muscle energetic reserves were highly depleted in Seine vs. Douarnenez fish. The Seine fish displaying a reduced capacity to manage the oxidative stress and a higher energetic metabolism. An increase in the content of muscle membrane phospholipids (sphingomyelin, phosphatidylserine, free sterols) was detected in the Seine vs. Douarnenez fish. The data integration allowed to hypothesize relationships between membrane phospholipids, xenobiotic metabolism, bioenergetics, and antioxidant defence. The genetic diversity considering neutral markers was maintained in the heavily polluted Seine population compared with the Douarnenez population. Finally, we suggest that the high physiological cost of tolerance to toxicants in the Seine flounder population could compromise its capacity to respond in the future to an additional stressor like warming waters in shallow depth. Thus, this population could be submitted to an ecological risk. Full article

Plastics pervade our environment and potentially release important quantities of plastic nanoparticles (NPs) from degradation in the environment. The purpose of this study was to examine the crowding effects of polystyrene NPs on lactate dehydrogenase (LDH) in vitro and following exposure to Hydra attenuata. First, LDH activity was measured in vitro in the presence of filamentous (F-)actin and NPs (50 and 100 nm diameter) to determine changes in viscosity and the fractal kinetics of LDH. The fractal dimension (fD) was also determined using the rescaled range analysis procedure. Secondly, these changes were examined in hydra exposed to NPs for 96h to concentrations of NPs. The data revealed that the addition of F-actin increased the rate of LDH at low substrate (pyruvate) concentrations compared to LDH alone with a gradual decrease in the rate with the addition of pyruvate, which is characteristic of the fractal behavior of enzymes in crowded environments. The addition of 50 and 100 nm NPs also produced these changes, which suggest that NPs could change the space properties of the LDH reaction. The fD was reduced to 0.85 and 0.91 with 50 and 100 nm NPs compared to 1.093 with LDH alone. Decrease in the fD was related with increased amplitudes and frequency in viscosity waves in the reaction media. Exposure of hydra to NPs confirmed the increase in LDH activity and the fD was significantly correlated with LDH activity (r = −0.5). Correction of LDH activity (residuals) still revealed an increase in LDH activity in hydra suggesting increased anaerobic metabolism by NPs. In conclusion, the presence of NPs in the intracellular space decreased the fD, which could influence LDH activity in organisms exposed to NPs. Full article

Journal of Xenobiotics was launched in 2011 with the mission to publish novel research articles in the fields of the occurrence and biochemical effects of xenobiotics on all living organisms and it has been published over the past nine years by PAGEPress Publications [...] Full article

The release of nanoplastics (NPs) from the weathering and degradation of plastics is an important environmental concern. Given their small sizes and their invasiveness in cells, methods for the detection of NPs in biological tissues are urgently needed. A simple fluorescence-based methodology for the detection of polystyrene NPs in biological tissues is proposed. The commercially available molecular rotor probe 9- (dicyanovinyl)-julolidine (DCVJ) has the properties to detect changes in hydrophobicity and microviscosity and was used to detect NPs. Increasing concentrations of 50 and 100 nm NPs in water and in tissue extracts were mixed with the DCVJ probe and the emission spectra determined between 480-800 nm at 450 nm excitation. The data revealed that NPs induces a second emission peak at 620 nm that differed from the normal spectra of the biological extract at 500 nm. A significant linear relationship was obtained for NPs of both sizes (r=0.98; P<0.001) with a theoretical limit of detection of 65 ng/mL. A simple and rapid microplate spectrofluorometric method for the semi-quantitative detection of polystyrene NPs in biological tissues is thus presented. Full article

Mangrove rivulus, Kryptolebias marmoratus, is a hermaphrodite fish capable of self-fertilization. This particularity allows to naturally produce highly homozygous and isogenic individuals. Despite the low genetic diversity, rivulus can live in extremely variable environments and adjust its phenotype accordingly. This species represents a unique opportunity to clearly distinguish the genetic and non-genetic factors implicated in adaptation and evolution, such as epigenetic mechanisms. It is thus a great model in aquatic ecotoxicology to investigate the effects of xenobiotics on the epigenome, and their potential long-term impacts. In the present study, we used the mangrove rivulus to investigate the effects of the neurotoxin ß-N-methylamino-L-alanine (BMAA) on larvae behaviors after 7 days exposure to two sub-lethal concentrations. Results show that BMAA can affect the maximal speed and prey capture (trials and failures), suggesting potential impacts on the organism’s fitness. Full article

Fungal spores are ubiquitous in indoor and outdoor air and their diversity and biomass quantity vary depending on the geographical location, environmental con- ditions, and the presence of sources such as hay, agricultural crops or growth on build- ing material [...]
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The UV-filter benzophenone and the anti-inflammatory diclofenac are commonly detected in the environment. The aim of this study was to assess the multigenerational effects of chronic exposure to low concentrations of these chemicals on toxicity and DNA methylation levels in the copepod Gladioferens pectinatus. Acute toxicity tests were conducted to determine the sensitivity of G. pectinatus to the chemicals. All chemicals impacted breeding, hatching and egg viability. Diclofenac (1 mg.L^-1) reduced the number of eggs per gravid female. Benzophenone (0.5 mg.L^-1) decreased egg hatching success. Exposure to the reference toxicant copper (0.02 mg.L^-1) led to unsuccessful hatching. Effects on DNA methylation was estimated by the percentage of 5- methylcytosine. The treatments resulted in strong differences in DNA methylation with increased methylation in the exposed animals. The two chemicals impacted both egg viability and the induction of differential DNA methylation, suggesting potential intra- and trans-generational evolutionary effects. Full article

Thiamethoxam (TMX), a second-generation neonicotinoid insecticide, is one of the most widely used insecticides in Algeria. The present study assessed the effects of repeated subchronic exposure to the commercial formulation of thiamethoxam (Actara^®, 25% WG) in albino male rats. The toxic effects of thiamethoxam (TMX) were studied biochemically and histopathologically. Twenty-eight male albino rats weighing between 226 and 243 g were randomly assigned to four groups. One group served as control, and the other three were served as experimental groups administered a neonicotinoid thiamethoxam (TMX; 26, 39 and 78 mg/kg/day) for 6 weeks. The effects of the insecticide on various biochemical parameters were evaluated at 2, 4 and 6 weeks. Histopathological studies were carried out in the liver, kidney, cerebellum and hippocampus at the end of the experiment. Changes in biochemical parameters glucose, ALT (alanine aminotransferase), AST (aspartate aminotransferase), γGT (gamma-glutamyltransferase) ALP (alkaline phosphatase) urea and creatinine were observed in treated-groups in a dose dependent manner when compared to the control. Histopathological alterations were more intense in male rats from the TMX high dose group than those from group 2 and 3. Based on these results, subchronic oral administration of thiamethoxam altered the biochemical parameters, which correlated with histopathological changes in the liver kidney and brain. Full article

Nearly 5 billion liters of untreated sewage was intentionally discharged in November 2015 in the St. Lawrence River (Canada) for reasons of major sewer system maintenance and to avoid jeopardizing the Montreal wastewater treatment plant [...]
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The purpose of this study was to examine the effects of dissolved and particulate compounds on quorum sensing in the marine luminescent bacterium Aliivibrio fisheri. Bacteria were exposed to increasing concentrations of CuSO₄ (Cu²⁺), gadolinium chloride (Gd³⁺), 20-nm silver nanoparticles (nanoAg) and 1-3 μm microplastic polyethylene beads for 250 min. During this period, luminescence measurements were taken at 5-min intervals. Toxicity was first examined by measuring luminescence output at 5-min and 30-min incubation time. Based on the effective concentration that decreases luminescence by 20% (EC20), the compounds were toxic at the following concentrations in decreasing toxicity: Cu²⁺ (3.2 mg/L) < nanoAg (3.4 mg/L, reported) < Gd³⁺ (34 mg/L) < microplastics (2.6 g/L). The data revealed that luminescence changed non-linearly over time. In control bacteria, luminescence changed at eight specific major frequencies between 0.04 and 0.27 cycle/min after Fourier transformation of time-dependent luminescence data. The addition of dissolved Cu²⁺ and Gd³⁺ eliminated the amplitude changes at these frequencies in a concentration-dependent manner, indicating loss of quorum sensing between bacteria at concentrations below EC20. In the presence of nanoAg and microplastic beads, the decreases in amplitudes were modest but compressed the luminescence profiles, with shorter frequencies appearing at concentrations well below EC20. Thus, loss of communication between bacteria occurs at non-toxic concentrations. In addition, with exposure to a mixture of the above compounds at concentrations that do not produce effects for Gd3+, nanoAg and microplastics, Cu²⁺ toxicity was significantly enhanced, suggesting synergy. This study revealed for the first time that small microplastic particles and nanoparticles can disrupt quorum sensing in marine bacteria. Full article