Journal of Xenobiotics

Δ9-tetrahydrocannabinol (THC) is one of the primary ingredients of cannabis plants and is responsible for the psychoactive properties of cannabis. While cannabidiol (CBD), the non-psychoactive compound from cannabis, has been shown to stimulate human epidermal melanogenesis, the effects of THC have not been addressed in human epidermal melanocytes. Moreover, to date, no study has tested the effects of these compounds on melanocytes differing in pigmentation, representative of different skin phototypes, which would be significant as different ethnicities are known to differentially metabolize these xenobiotics. Herein, the effects of THC were studied and compared alongside CBD in human epidermal melanocytes derived from lightly-pigmented (HEMn-LP; Caucasian) and darkly-pigmented (HEMn-DP; African-American) cells over a chronic exposure of 6 d. Results demonstrated that both compounds displayed cytotoxicity at 4 µM but stimulated melanin synthesis and tyrosinase activity in a similar manner in LP and DP cells at nontoxic concentrations of 1–2 µM. However, THC and CBD showed a differential effect on dendricity in both cells; THC and CBD reversibly increased dendricity in LP cells while there was no significant change in DP cells. THC and CBD induced higher levels of reactive oxygen species (ROS) in LP cells while there was no change in the ROS levels in DP cells. In summary, although THC was relatively less cytotoxic as compared to CBD to both LP and DP cells, it exhibited a similar capacity as CBD to stimulate melanin synthesis and export in LP cells which was accompanied by a significant oxidative stress. DP cells were relatively resistant to the effects of both THC and CBD which might implicate the protective effects conferred by melanin in dark-skinned individuals. Full article

Introduction: Type 2 diabetes (T2DM), which is more prevalent (more than 90% of all diabetes cases) and the main driver of the diabetes epidemic, now affects 5.9% of the world’s adult population, with almost 80% of the total in developing countries. At present, 537 million adults (20–79 years) are living with diabetes—1 in 10. This number is predicted to rise to 643 million by 2030 and 783 million by 2045. In India, reports show that 69.2 million people are living with diabetes (8.7%) as per 2015 data. Long-term metformin treatment is a known pharmacological cause of vitamin B12 (Vit B12) deficiency, as was evident within the first 10–12 years after it started to be used. Methods: This was a cross-sectional study conducted in the Postgraduate Department of Medicine in one of the tertiary hospitals in Kashmir. A total of 1600 consecutive patients with T2DM were taken for the study. Out of which 700 patients met the inclusion criteria. These 700 patients were divided into two groups: those taking metformin, and those who were not on metformin. Cumulative metformin doses were recorded in patients taking metformin, using history of dose and duration of treatment. Serum Vit B12 levels were taken for all patients. Based on the results of Vit B12 levels, patients were classified into normal levels (20 pmol/L), possible B12 deficiency (150–220 pmol/l), and definite deficiency (<150 pmol/L). Results: Our results depicted that patients on prolonged metformin therapy showed an increase in Vit B12 deficiency by 11.16%. The prevalence of clinical neuropathy in the metformin-exposed group was 45%, whereas, a prevalence of 31.8% was found in the non-metformin group. The mean age of patients with neuropathy was higher than those without neuropathy (59.01 ± 7.14 vs. 49.95 ± 7.47) (p-value < 0.514, statistically insignificant). Conclusions: In our study, we found that metformin use is associated with Vit B12 deficiency, which is dependent upon the cumulative dose of metformin. Importantly, prolonged metformin use is also associated with an increase in the prevalence of clinical neuropathy. Full article

Ecotoxicity investigations of plastic nanoparticles (NPs) should pay more attention to their ability to pass barriers, accumulate, and initiate toxicity in cells. The purpose of this study was to develop a simple size exclusion chromatography (SEC) methodology to measure plastic NPs in biological tissues. A SEC column was prepared using a high-resolution gel for large macromolecules to separate plastic NPs from the protein/lipid pools in tissues. It was necessary to prepare the samples in high salt and non-ionic detergent (0.5 M NaCl and 0.2% Tween-20) and apply 0.2% Tween-20 containing 14 mM NaCl for the elution buffer to limit proteins adsorption to NPs. This methodology was able to resolve 50 and 100 nm polystyrene NPs from the protein/lipid pools in tissue homogenates. The fluorescent dye neutral red (NR) was also used for transparent NPs. Moreover, a sample fractionation step was also proposed for plastic NPs concentration using a salting-out methodology with saturated NaCl (5 M) and acetonitrile. Polystyrene NPs partition in acetonitrile, which were further analyzed by SEC. This methodology was tested in two case studies with clams collected in a high boat traffic (harbor) area and with caged freshwater mussels downstream of a large urban area. Although the present methodology was developed with polystyrene NPs it should be amenable to other plastic polymers that react with the NR fluorescent probe. Full article

(1) Background: Nanocellulose is an innovative engineered nanomaterial with an enormous potential for use in a wide array of industrial and biomedical applications and with fast growing economic value. The expanding production of nanocellulose is leading to an increased human exposure, raising concerns about their potential health effects. This study was aimed at assessing the potential toxic and genotoxic effects of different nanocelluloses in two mammalian cell lines; (2) Methods: Two micro/nanocelluloses, produced with a TEMPO oxidation pre-treatment (CNFs) and an enzymatic pre-treatment (CMFs), and cellulose nanocrystals (CNCs) were tested in osteoblastic-like human cells (MG-63) and Chinese hamster lung fibroblasts (V79) using the MTT and clonogenic assays to analyse cytotoxicity, and the micronucleus assay to test genotoxicity; (3) Results: cytotoxicity was observed by the clonogenic assay in V79 cells, particularly for CNCs, but not by the MTT assay; CNF induced micronuclei in both cell lines and nucleoplasmic bridges in MG-63 cells; CMF and CNC induced micronuclei and nucleoplasmic bridges in MG-63 cells, but not in V79 cells; (4) Conclusions: All nanocelluloses revealed cytotoxicity and genotoxicity, although at different concentrations, that may be related to their physicochemical differences and availability for cell uptake, and to differences in the DNA damage response of the cell model. Full article

Biopolymers such as chitosan and gum acacia are used for nanotechnological applications due to their biosafety and ecofriendly nature. The commercial fungicide mancozeb (M) was loaded into chitosan–gum acacia (CSGA) polymers to form nanocomposite (NC) CSGA-M (mancozeb-loaded) measuring 363.6 nm via the ionic gelation and polyelectrolyte complexation method. The physico-chemical study of nano CSGA-M was accomplished using dynamic light scattering (DLS), scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). Nano CSGA-M-1.0 (containing 1.0 mg/mL mancozeb) at 1.5 ppm demonstrated a maximum inhibition (83.8 ± 0.7%) against Alternaria solani, while Sclerotinia sclerotiorum exhibited a 100% inhibition at 1.0 and 1.5 ppm through the mycelium inhibition method. Commercial mancozeb showed an inhibition of 84.6 ± 0% and 100%, respectively, for both fungi. In pot house conditions, NCs were found to exhibit good antimicrobial activity. Disease control efficiency (DCE, in %) in pathogen-treated plants for CSGA-M-1.0 was 64.6 ± 5.0 and 60.2 ± 1.4% against early blight and stem rot diseases, respectively. NCs showed lower cytotoxicity than commercial mancozeb at the given concentration. In conclusion, both in vitro and in vivo antifungal efficacy for nano CSGA-M was found to be quite comparable but less toxic than mancozeb to Vero cell lines; thus, in the future, this formulation may be used for sustainable agriculture. Full article

The endocrine disruptors are mostly small organic molecules developed for numerous and very diverse industrial applications. They essentially act through nuclear receptors with small and hydrophobic endogenous ligands. Nevertheless, potential adverse effects through membrane hormone receptors cannot be ruled out, and have indeed been observed. The present paper reviews how orthosteric and allosteric binding sites of the different families of membrane receptors can be targets for man-made hydrophobic molecules (components of plastics, paints, flame retardants, herbicides, pesticides, etc.). We also review potential target proteins for such small hydrophobic molecules downstream of membrane receptors at the level of their intracellular signaling pathways. From the currently available information, although endocrine disruptors primarily affect nuclear receptors’ signaling, membrane receptors for hormones, cytokines, neuro-mediators, and growth factors can be affected as well and deserve attention. Full article

Chemical risk assessment in the context of the risk analysis framework was initially designed to evaluate the impact of hazardous substances or xenobiotics on human health. As the need of multiple stressors assessment was revealed to be more reliable regarding the occurrence and severity of the adverse effects in the exposed organisms, the cumulative risk assessment started to be the recommended approach. As toxicant mixtures and their “cocktail effects” are considered to be main hazards, the most important exposure for these xenobiotics would be of dietary and environmental origin. In fact, even a more holistic prism should currently be considered. In this sense, the definition of One Health refers to simultaneous actions for improving human, animal, and environmental health through transdisciplinary cooperation. Global policies necessitate going beyond the classical risk assessment for guaranteeing human health through actions and implementation of the One Health approach. In this context, a new perspective is proposed for the integration of microbiome biomarkers and next generation probiotics potentially impacting and modulating not only human health, but plant, animal health, and the environment. Full article

Psychedelics extracted from plants have been used in religious, spiritual, and mystic practices for millennia. In 1957, Dr. Hofmann identified and synthesized the prodrug psilocybin, a substance present in more than 200 species of psychedelic mushrooms. Although there were limitations related to the scientific design of many studies, clinical observations performed during the 1950s and 1960s showed a potential therapeutic effect of psilocybin for patients affected by depressive symptoms, anxiety, and conversion disorder. Psilocybin was classed as a schedule I substance in 1970, but the fascination with psychedelics has remained almost unchanged over time, promoting a new scientific interest starting in the 1990s. Recent studies have provided further evidence supporting the suggestive hypothesis of the therapeutic use of psilocybin for treating various psychiatric disorders, including pathological anxiety, mood depressive disorder, and addiction. Full article

Glyphosate-based herbicide has been the first choice for weed management worldwide since the 1970s, mainly due to its efficacy and reported low toxicity, which contributed to its high acceptance. Many of the recent studies focus solely on the persistence of pesticides in soils, air, water or food products, or even on the degree of exposure of animals, since their potential hazards to human health have raised concerns. Given the unaware exposure of the general population to pesticides, and the absence of a significant number of studies on occupational hazards, new glyphosate-induced toxicity data obtained for both residual and acute doses should be analyzed and systematized. Additionally, recent studies also highlight the persistence and toxicity of both glyphosate metabolites and surfactants present in herbicide formulations. To renew or ban the use of glyphosate, recently published studies must be taken into account, aiming to define new levels of safety for exposure to herbicide, its metabolites, and the toxic excipients of its formulations. This review aims to provide an overview of recent publications (2010–present) on in vitro and in vivo studies aimed at verifying the animal toxicity induced by glyphosate, its metabolite aminomethylphosphonic acid (AMPA) and glyphosate-based formulations, evaluated in various experimental models. Apart from glyphosate-induced toxicity, recent data concerning the role of surfactants in the toxicity of glyphosate-based formulations are discussed. Full article

Background and objectives: Honey products contain a lot of compounds, such as vitamins, enzymes, and minerals, which make honey and its products a great antioxidant with a critical role in health status. It is well accepted that honey and propolis can improve a lot of health problems when they are consumed in certain quantities. The objective of this study is to help regular blood donors improve their health status after donation. Material and methods: Eighty regular blood donor volunteers—30 males aged 19–61 and 30 females aged 21–64—were divided into 4 groups: group A (n = 20) consumed 2 spoons of Greek honey and 1 drop of propolis per day for 1 month, group B (n = 20) consumed 2 spoons of honey per day for 1 month, group C (n = 20) consumed 1 drop of propolis per day, and group D (n = 20) did not consume any Greek honey products. Blood samples were collected from all participants just before the consumption of the products, one month after the consumption, and six months after honey product consumption had ceased. All samples were analyzed for reactive oxygen species (ROS), lipid profiles, and ferritin levels. Results: The ROS were significantly (p < 0.05) lower in groups A, B, and C after the honey product consumption and increased significantly again after six months. No significant differences in lipid profiles were observed. Only triglyceride levels were increased after six months in all groups. On the other hand, ferritin levels were not statistically significantly decreased after six months in groups A and B, while they were increased in group C. Conclusions: In the present study, statistically significant decreases in ROS status was found after a small dose of honey product consumption, indicating a diet with an extra small dose of honey products after blood donation. Full article

Microplastics (MPs) are ubiquitous in environmental media, and their harmful effects on MPs on the ecosystem have attracted more and more attention. Once released into the environment, MPs can trigger oxidative degradation through ultraviolet (UV) to cause photoaging. Photoaging significantly affects the properties of MPs, which leads to changing their environmental behaviors and increasing environmental risks. In this review, the generation of MPs under UV irradiation and the influence of environmental factors on the photoaging of MPs were discussed. Photoaging of MPs is an important process affecting the migration, transformation and interaction of pollutants in water and soil. In order to fully predict the fate and environmental interaction of MPs, more researches are needed in the future to explore the photoaging behavior of different types of MPs under natural environmental conditions. Full article

With the rise in concern about GMOs and pesticides on human health, we have utilized Drosophila melanogaster as a model organism for understanding the effects of Roundup-Ready^® GMO diets on health. We recorded dietary behavior during and after exposure to a medium containing GMO or non-GMO corn, Roundup^® in organic corn medium, and sucrose with or without one of the two Roundup^® formulations. No differences in behavior were observed when Drosophila were exposed to a medium containing Roundup-Ready^® GMO or non-GMO corn. Drosophila can detect and refrain from eating sucrose containing one Roundup^® formulation, Ready-to-Use, which contains pelargonic acid in addition to glyphosate as an active ingredient. Drosophila exhibited dose-dependent increased consumption of sucrose alone after exposure to a medium containing either Roundup^® formulation. This may indicate that flies eating a medium with Roundup^® eat less and were thus hungrier when then given sucrose solution; that a medium with Roundup^® is more difficult to digest; or that a medium with Roundup^® is less nutritious, as would be the case if nutritionally important microbes grew on control medium, but not one containing Roundup^®. Full article

With the advancements of science, antibiotics have emerged as an amazing gift to the human and animal healthcare sectors for the treatment of bacterial infections and other diseases. However, the evolution of new bacterial strains, along with excessive use and reckless consumption of antibiotics have led to the unfolding of antibiotic resistances to an excessive level. Multidrug resistance is a potential threat worldwide, and is escalating at an extremely high rate. Information related to drug resistance, and its regulation and control are still very little. To interpret the onset of antibiotic resistances, investigation on molecular analysis of resistance genes, their distribution and mechanisms are urgently required. Fine-tuned research and resistance profile regarding ESKAPE pathogen is also necessary along with other multidrug resistant bacteria. In the present scenario, the interaction of bacterial infections with SARS-CoV-2 is also crucial. Tracking and in-silico analysis of various resistance mechanisms or gene/s are crucial for overcoming the problem, and thus, the maintenance of relevant databases and wise use of antibiotics should be promoted. Creating awareness of this critical situation among individuals at every level is important to strengthen the fight against this fast-growing calamity. The review aimed to provide detailed information on antibiotic resistance, its regulatory molecular mechanisms responsible for the resistance, and other relevant information. In this article, we tried to focus on the correlation between antimicrobial resistance and the COVID-19 pandemic. This study will help in developing new interventions, potential approaches, and strategies to handle the complexity of antibiotic resistance and prevent the incidences of life-threatening infections. Full article

The current scenario of male infertility is not yet fully elucidated; however, there is increasing evidence that it is associated with the widespread exposure to endocrine-disrupting chemicals (EDCs), and in particular to obesogens. These compounds interfere with hormones involved in the regulation of metabolism and are associated with weight gain, being also able to change the functioning of the male reproductive axis and, consequently, the testicular physiology and metabolism that are pivotal for spermatogenesis. The disruption of these tightly regulated metabolic pathways leads to adverse reproductive outcomes. The permanent exposure to obesogens has raised serious health concerns. Evidence suggests that obesogens are one of the leading causes of the marked decline of male fertility and key players in shaping the future health outcomes not only for those who are directly exposed but also for upcoming generations. In addition to the changes that lead to inefficient functioning of the male gametes, obesogens induce alterations that are “imprinted” on the genes of the male gametes, establishing a link between generations and contributing to the transmission of defects. Unveiling the molecular mechanisms by which obesogens induce toxicity that may end-up in epigenetic modifications is imperative. This review describes and discusses the suggested molecular targets and potential mechanisms for obesogenic–disrupting chemicals and the subsequent effects on male reproductive health. Full article

Malaria and Leishmaniasis are two major parasitic diseases, endemic in large areas of tropical countries with high morbidity and mortality across the world. Nanoparticles in small sizes are specifically considered in medicine due to their ability to enter the cells, control the distribution of the administered drug and carry the drug specifically to the place of action. The present study aims to introduce the application of silica nanoparticles as new promising nanotools in malaria and leishmaniasis treatment. Ion doped silica nanomaterials revealed antileishmanial activities indicating the positive role of calcium, magnesium and copper to the surface of the particles against Leishmania parasites. Artemisinin-loaded nanoparticles presented the most promising antiparasitic properties with a sustained release able to overcome the parasite invasion. The sustainable release of artemisinin guarantee both the maintenance of its potential efficacy and also introduce an administration of drug to avoid subsequent drug resistance. Full article

Photodegradation (photolysis) causes the breakdown of organic pesticides molecules by direct or indirect solar radiation energy. Flucetosulfuron herbicide often encounters water bodies. For this reason, it is important to know the behavior of the compound under these stressed conditions. In this context, photodegradation of flucetosulfuron, a sulfonylurea-based herbicide, has been assessed in aqueous media in the presence of photocatalyst TiO₂ and photosensitizers (i.e., H₂O_2, humic acid, and KNO₃) under the influence of ultraviolet (UV) irradiation. The influence of different water systems was also assessed during the photodegradation study. The photodegradation followed the first-order reaction kinetics in each case. The metabolites after photolysis were isolated in pure form by column chromatographic method and characterized using the different spectral data (i.e., XRD, IR, NMR, UV-VIS, and mass spectrometry). The structures of these metabolites were identified based on the spectral data and the plausible photodegradation pathways of flucetosulfuron were suggested. Based on the findings, photocatalyst TiO₂ with the presence of ultraviolet irradiation was found effective for the photodegradation of toxic flucetosulfuron residues under aqueous conditions. Full article

Xenobiotics are compounds of synthetic origin, usually used for domestic, agricultural, and industrial purposes; in the environment, they are present in micropollutant concentrations and high concentrations (using ng/L to µg/L units). Xenobiotics can be categorized according to different criteria, including their nature, uses, physical state, and pathophysiological effects. Their impacts on humans and the environment are non-negligible. Prolonged exposure to even low concentrations may have toxic, mutagenic, or teratogenic effects. Wastewater treatment plants that are ineffective at minimizing the release of xenobiotic compounds are one of the main sources of xenobiotics in the environment (e.g., xenobiotic compounds reach the environment, affecting both humans and animals). In order to minimize the negative impacts, various laws and regulations have been adopted in the EU and across the globe, with an emphasis on xenobiotics removal from the environment, in a way that is economically, environmentally, and socially acceptable, and will not result in their accumulation, or creation of compounds that are more harmful. Detection methods allow detecting even small concentrations of xenobiotics in samples, but the problem is the diversity and mix of compounds present in the environment, in which it is not known what their effects are). In this review, the division of xenobiotics and their detection methods will be presented. Full article

Per- and polyfluoroalkyl substances (PFASs) are persistent environmental pollutants that are commonly found in the human body due to exposures via drinking water, surfactants used in consumer materials, and aqueous film-forming foams (AFFFs). PFAS exposure has been linked to adverse health effects such as low infant birth weights, cancer, and endocrine disruption, though increasingly studies have demonstrated that they may perturb metabolic processes and contribute to dysfunction. This scoping review summarizes the chemistry of PFAS exposure and the epidemiologic evidence for associations between exposure to per- and polyfluoroalkyl substances and the development of diabetes, hyperglycemia, and/or insulin resistance. We identified 11 studies on gestational diabetes mellitus, 3 studies on type 1 diabetes, 7 studies on type 2 diabetes, 6 studies on prediabetes or unspecified diabetes, and 15 studies on insulin resistance or glucose tolerance using the SCOPUS and PubMed databases. Approximately 24 reported positive associations, 9 negative associations, 2 non-linear associations, and 2 inverse associations, and 8 reported no associations found between PFAS and all diabetes search terms. Cumulatively, these data indicate the need for further studies to better assess these associations between PFAS exposure and diabetes. Full article