Xenobiotic Components Research Articles

Alterations in viscera histoarchitecture and organosomatic index as biomarkers of toxicity induced by Aba-Eku and Olusosun solid waste landfill leachates in Rattus norvegicus.

Solid waste disposal generates leachate, a mixture of deleterious chemical, physical and microbial contaminants, which poses risk to human and wildlife health. Leachate toxicity on relative organ weight and histopathology of important viscera in mammalian body is scarce. Leachate induced toxic effects on organosomatic indices and histopathology of vital mammalian organs were investigated. Wister rats were orally exposed to 1 - 25 % of raw and simulated leachates from Aba-Eku and Olusosun landfills for 30 days. At post-exposure, organosomatic index and histoarchitectural assessment of major viscera (heart, spleen, thymus and lungs) were conducted. The physico-chemical and organic compositions of the leachates were analysed using standard protocol. The tested leachates decreased weekly and terminal body weights, and altered organosomatic index of examined viscera in rats. The histoarchitecture of the investigated viscera revealed pathologies that ranged from mild to severe degeneration, cellular infiltration, haemorrhage, congestion, necrosis, disorganization of tissues and vacuolations. Others include increased histiocytes within the bronchial associated lymphoid, lymphoid depletions, haemosiderin deposits and apoptosis were observed in the examined viscera. Physico-chemical analysis of the leachates showed different concentrations of toxic metals, PAHs and PCBs that were higher than national and international permissible limits allowed in wastewaters. The physico-chemical compositions of the leachates are capable of eliciting the observed alterations in organosomatic indices and histopathological lesions in mammalian viscera. Xenobiotic components of the leachates possibly generated free radicals and/or directly disrupted the organ architectures. These findings suggest health risk to wildlife and human population exposed to emissions from waste landfills.

A Review on Potentiality of Marine Algae in Environmental Sustainability

Marine algae are substantial in their natural habitats and even more now in the world of green technology. The essential products extracted from marine algae are highly analyzed areas in impulsive product research. The diverse development in the employment of algae to conquer the environmental complications has stimulated the assurance of achieving the sustainability. The word sustainability represents the comprehensively productive improvements of the environment that encircle an amble compelling and their management. The hasty growth of the population and rapid civilization has led mankind to the exhaustive exploitation of nature and its vibrant resources. However, today humans have realized the catastrophes instigated because of their preceding errors and have already been facing future sustenance challenges. Today, it has turned out to be a challenging task to discover and to develop an eco-friendly, cost-effective and cutting-edge strategies to encounter the current sustainability glitches like, sustainable agriculture solutions, feedstock crisis, pollution, carbon neutrality, industrial effluents and waste water treatment, energy crisis and xenobiotic components that contaminates the natural ecosystem. Marine algae are very good source of bioactive compounds as it is rich in dietary fiber, omega 3 fatty acids, carotenoids, vitamins and minerals. They are effectively crucial due to its extensive spectrum of applications as food, fodder, pisciculture, fertilizer etc. Thus the present review discusses the far ranging opportunities of using marine algae for environmental sustainability

Biochemical and structural characterization of an aromatic ring-hydroxylating dioxygenase for terephthalic acid catabolism.

SignificanceMore than 400 million tons of plastic waste is produced each year, the overwhelming majority of which ends up in landfills. Bioconversion strategies aimed at plastics have emerged as important components of enabling a circular economy for synthetic plastics, especially those that exhibit chemically similar linkages to those found in nature, such as polyesters. The enzyme system described in this work is essential for mineralization of the xenobiotic components of poly(ethylene terephthalate) (PET) in the biosphere. Our description of its structure and substrate preferences lays the groundwork for invivo or ex vivo engineering of this system for PET upcycling.

High-Throughput Identification of Organic Compounds from Polygoni Multiflori Radix Praeparata (Zhiheshouwu) by UHPLC-Q-Exactive Orbitrap-MS.

Polygoni Multiflori Radix Praeparata (PMRP), as the processed product of tuberous roots of Polygonum multiflorum Thunb., is one of the most famous traditional Chinese medicines, with a long history. However, in recent years, liver adverse reactions linked to PMRP have been frequently reported. Our work attempted to investigate the chemical constituents of PMRP for clinical research and safe medication. In this study, an effective and rapid method was established to separate and characterize the constituents in PMRP by combining ultra-high performance liquid chromatography with hybrid quadrupole-orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS). Based on the accurate mass measurements for molecular and characteristic fragment ions, a total of 103 compounds, including 24 anthraquinones, 21 stilbenes, 15 phenolic acids, 14 flavones, and 29 other compounds were identified or tentatively characterized. Forty-eight compounds were tentatively characterized from PMRP for the first time, and their fragmentation behaviors were summarized. There were 101 components in PMRP ethanol extract (PMRPE) and 91 components in PMRP water extract (PMRPW). Simultaneously, the peak areas of several potential xenobiotic components were compared in the detection, which showed that PMRPE has a higher content of anthraquinones and stilbenes. The obtained results can be used in pharmacological and toxicological research and provided useful information for further in vitro and in vivo studies.

Efficient isolation and proliferation of human adipose-derived mesenchymal stromal cells in xeno-free conditions.

Classical methods used for culture of adipose-derived mesenchymal stromal cells (ADSCs) use xenobiotic components, which may present a potential risk for biological contamination and/or elicit immunological reactions. Therefore, the aim of this study was to establish a xeno-free methodology for the isolation and proliferation of human ADSCs (hADSCs). hADSCs were isolated by enzymatic digestion or mechanical dissociation and cultured in the presence of fetal bovine serum or human platelet lysate. Proliferation curves were performed as a function of time from the cell culture and used to calculate the population doubling time. Immunophenotyping and differentiation tests were used to identify and characterize the hADSCs. Human ADSCs isolated and cultured in conventional or xenobiotic-free conditions peaked at different days but achieved similar maximum proliferation. The hADSCs differentiation ability was similar in all groups. The characterization of hADSCs by flow cytometry showed low contamination of the cultures by other cell types. The xenobiotic-free methodology described in this study is a feasible and reproducible alternative for isolation and proliferation of hADSCs. This methodology is in accordance with the recommendations of the National Health Surveillance Agency, which proposes avoidance of xenobiotic products.

Microbiota associated with the skin, gills, and gut of the fish Parachondrostoma toxostoma from the Rhône basin

Abstract The close relationships between hosts and their microbiota underlie the current concept of holobionts. This biological entity enlarges our perception of the genomic diversity supported by individuals/species and the potential abilities of hosts to respond to the environment. We investigated a total of 54 specimens of the sofie fish Parachrondrostoma toxostoma (Pt) for the taxonomic and functional composition of microbiota associated with the skin, gills, and gut tissues. Five wild populations from the Ardèche and Durance river basins in the Mediterranean part of the large catchment of the Rhône (southern France) were compared. We found that the skin microbiota was more diverse and variable in bacterial community composition than the gut microbiota. These differences suggest that different deterministic factors underlie the composition of these bacterial communities, resulting in tissue‐specific variation of the microbiota composition between wild fish populations inhabiting two rivers. Microbiota diversity and composition differed between wild Pt populations at both regional and local spatial scales. Using the Picrust tool, the taxonomic variation of the microbiota composition in the river fish populations could be associated with the enrichment of predicted metabolic pathways. In particular, carbohydrate metabolism was more represented and xenobiotic biodegradation pathways less represented in the gut microbiota of Pt populations from the Ardèche than of those from the Durance. This result suggests variability in the ability to acclimate to environmental features through the assimilation of food resources from plants and the detoxification of xenobiotic components. This study opens perspectives in the detection of subtle shifts in environmental features through the description of the microbiota composition, and in the potential prediction of the functional capacities of species to acclimate.

The Role of Nitric Oxide in Regulating Intestinal Redox Status and Intestinal Epithelial Cell Functionality.

Important functions of intestinal epithelial cells (IECs) include enabling nutrient absorption to occur passively and acting as a defense barrier against potential xenobiotic components and pathogens. A compromise to IEC function can result in the translocation of bacteria, toxins, and allergens that lead to the onset of disease. Thus, the maintenance and optimal function of IECs are critically important to ensure health. Endogenous biosynthesis of nitric oxide (NO) regulates IEC functionality both directly, through free radical activity, and indirectly through cell signaling mechanisms that impact tight junction protein expression. In this paper, we review the current knowledge on factors that regulate inducible nitric oxide synthase (iNOS) and the subsequent roles that NO has on maintaining IECs’ intestinal epithelial barrier structure, functions, and associated mechanisms of action. We also summarize important findings on the effects of bioactive dietary food components that interact with NO production and affect downstream intestinal epithelium integrity.

Human Pluripotent Stem Cell Culture: Current Status, Challenges, and Advancement.

Over the past two decades, human embryonic stem cells (hESCs) have gained attention due to their pluripotent and proliferative ability which enables production of almost all cell types in the human body in vitro and makes them an excellent tool to study human embryogenesis and disease, as well as for drug discovery and cell transplantation therapies. Discovery of human-induced pluripotent stem cells (hiPSCs) further expanded therapeutic applications of human pluripotent stem cells (PSCs). hPSCs provide a stable and unlimited original cell source for producing suitable cells and tissues for downstream applications. Therefore, engineering the environment in which these cells are grown, for stable and quality-controlled hPSC maintenance and production, is one of the key factors governing the success of these applications. hPSCs are maintained in a particular niche using specific cell culture components. Ideally, the culture should be free of xenobiotic components to render hPSCs suitable for therapeutic applications. Substantial efforts have been put to identify effective components, and develop culture conditions and protocols, for their large-scale expansion without compromising on quality. In this review, we discuss different media, their components and functions, including specific requirements to maintain the pluripotent and proliferative ability of hPSCs. Understanding the role of culture components would enable the development of appropriate conditions to promote large-scale, quality-controlled expansion of hPSCs thereby increasing their potential applications.

Microbiome-Linked Crosstalk in the Gastrointestinal Exposome towards Host Health and Disease

The gastrointestinal exposome represents the integration of all xenobiotic components and host-derived endogenous components affecting the host health, disease progression and ultimately clinical outcomes during the lifespan. The human gut microbiome as a dynamic exposome of commensalism continuously interacts with other exogenous exposome as well as host sentineling components including the immune and neuroendocrine circuit. The composition and diversity of the microbiome are established on the basis of the luminal environment (physical, chemical and biological exposome) and host surveillance at each part of the gastrointestinal lining. Whereas the chemical exposome derived from nutrients and other xenobiotics can influence the dynamics of microbiome community (the stability, diversity, or resilience), the microbiomes reciprocally alter the bioavailability and activities of the chemical exposome in the mucosa. In particular, xenobiotic metabolites by the gut microbial enzymes can be either beneficial or detrimental to the host health although xenobiotics can alter the composition and diversity of the gut microbiome. The integration of the mucosal crosstalk in the exposome determines the fate of microbiome community and host response to the etiologic factors of disease. Therefore, the network between microbiome and other mucosal exposome would provide new insights into the clinical intervention against the mucosal or systemic disorders via regulation of the gut-associated immunological, metabolic, or neuroendocrine system.

Abstract 20069: Serum-Free Culture Conditions Support Human Cardiac Stem Cell Outgrowth

Introduction: Autologous cardiac stem cell (CSC) therapies represent an emerging treatment option for patients with congestive heart failure. Unfortunately, straightforward translation to the clinic is limited by traditional culture conditions that are supplemented by ill-defined or xenobiotic components such as fetal bovine serum. As such, overcoming these barriers is the next critical step in developing next generation CSC therapies for clinical use. Methods/Results: Transition of CSC culture methods to serum-free, xeno-free culture conditions demonstrated negligible effects on the overall numbers of cells cultured with equivalent cardiac (c-Kit+; 7.8±0.2 %, p=0.34) and mesenchymal (CD90+; 32±7 %, p=0.57) progenitor content as compared to standard culture conditions. Flow cytometry morphometry demonstrated that serum free cells provide a smaller, more homogeneous cell product. Exposure to hypoxic stress conditions demonstrated equivalent secretion of SDF-1α, SCF, HGF, and VEGF-A with reduced production of the pro-inflammatory cytokine IL-6 from serum-free cells (7±2 fold less; p=0.005). Despite differences in cytokine production, conditioned media from serum-free CSCs promoted similar new vessel formation (37±5 vs. 41±7 % of positive control within a HUVEC tube formation assay; p=0.69) and circulating stem cell recruitment (39±9 vs. 47±12% of the positive control within a transwell assay, p=0.64) when compared to media conditioned by standard cultures. Storage of cell suspensions at 4°C had negligible effects on 12 hour viability (95.3±1.6%, p=0.50), suggesting a shelf life sufficient for transport between institutions. Finally, injection of CSCs through a clinically approved coronary artery perfusion catheter did not alter cell viability (99.2±1.7 % after delivery, p=0.77) while ensuring successful product delivery to the peri-infarct zone. Conclusions: Transitioning CSCs to clinically acceptable protocols provides a more uniform cell product ready for clinical delivery. These findings represent the first published evidence that altered serum-free xeno-free culture conditions can provide a superior CSC cell product with the potential for ready translation to clinical use.

The effect of isolation and culture methods on epithelial stem cell populations and their progeny—toward an improved cell expansion protocol for clinical application

Background aimsThe use of cultured epithelial keratinocytes in the treatment of burns and skin graft donor sites is well established in clinical practice. The most widely used culture method for clinical use was originally developed by Rheinwald and Green 40 years ago. This system uses irradiated mouse dermal fibroblasts as a feeder cell layer to promote keratinocyte growth, a process that is costly and labor-intensive for health care providers. The medium formulation contains several components of animal origin, which pose further safety risks for patients. Improvements and simplification in the culturing process would lead to clear advantages: improved safety through reduction of xenobiotic components and reduction in cost for health care providers by dispensing with feeder cells. MethodsWe compared the Rheinwald and Green method to culture in three commercially available, feeder-free media systems with defined/absent components of animal origin. ResultsDuring the isolation process, short incubation times in high-strength trypsin resulted in increased numbers of liberated keratinocyte stem cells compared with longer incubation times. All three commercially available media tested in this study could support the expansion of keratinocytes, with phenotypes comparable to cells expanded using the established Rheinwald and Green method. Growth rates varied, with two of the media displaying comparable growth rates, whereas the third was significantly slower. Discussion.Our study demonstrates the suitability of such feeder-free media systems in clinical use. It further outlines a range of techniques to evaluate keratinocyte phenotype when assessing the suitability of cells for clinical application.

OPTIMIZATION OF CARDIAC STEM CELLS FOR CLINICAL TRANSLATION

Autologous cardiac stem cell (CSC) therapies represent an emerging treatment option for patients with congestive heart failure. Unfortunately, straightforward translation to the clinic is limited by traditional culture conditions that are supplemented by ill-defined or xenobiotic components. As such, overcoming these barriers is the next critical step in developing next generation CSC therapies for clinical use.

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Cancer and degenerative diseases are major causes of morbidity and death, derived from the permanent modification of key biopolymers such as DNA and regulatory proteins by usually smaller, reactive molecules, present in the environment or generated from endogenous and xenobiotic components by the body's own biochemical mechanisms (molecular adducts). In particular, protein adducts with organic electrophiles have been studied for more than 30 [see, e.g., Calleman et al., 1978] years essentially for three purposes: (a) as passive monitors of the mean level of individual exposure to specific chemicals, either endogenously present in the human body or to which the subject is exposed through food or environmental contamination; (b) as quantitative indicators of the mean extent of the individual metabolic processing which converts a non-reactive chemical substance into its toxic products able to damage DNA (en route to cancer induction through genotoxic mechanisms) or key proteins (as in the case of several drugs, pesticides or otherwise biologically active substances); (c) to relate the extent of protein modification to that of biological function impairment (such as enzyme inhibition) finally causing the specific health damage. This review describes the role that contemporary mass spectrometry-based approaches employed in the qualitative and quantitative study of protein-electrophile adducts play in the discovery of the (bio)chemical mechanisms of toxic substances and highlights the future directions of research in this field. A particular emphasis is given to the measurement of often high levels of the protein adducts of several industrial and environmental pollutants in unexposed human populations, a phenomenon which highlights the possibility that a number of small organic molecules are generated in the human organism through minor metabolic processes, the imbalance of which may be the cause of "spontaneous" cases of cancer and of other degenerative diseases of still uncharacterized etiology. With all this in mind, it is foreseen that a holistic description of cellular functions will take advantage of new analytical methods based on time-integrated metabolomic measurements of a new biological compartment, the "adductome," aimed at better understanding integrated organism response to environmental and endogenous stressors.

Electrokinetic extraction of surfactants and heavy metals from sewage sludge

Waste management represents a quite serious problem involving aspects of remediation technologies and potential re-utilization in different fields of human activities. Of course, wastes generated in industrial activities deserve more attention because of the nature and amount of xenobiotic components, often difficult to be eliminated. However, also ordinary wastes of urban origin are drawing more and more attention, depending on the concentration of noxious substances like surfactants and some heavy metal, which may eventually require expensive disposal. In the present paper, a research has been carried out on the application of electrokinetic treatments for the abatement of the above xenobiotic components from sewage sludge generated in urban wastewater treatment plants. Experiments were carried out on a laboratory scale, in a 250 mm × 50 mm × 100 mm cell, using 250–300 g of sludge for each test and current densities between 2.4 and 5.7 mA cm −2. As a general result, quite significant abatements of heavy-metal ions and surfactants were achieved, with relatively low energy consumption.

Metabolism of 2-fluoro-4-iodoaniline in earthworm Eisenia veneta using 19F-NMR spectroscopy, HPLC-MS, and HPLC-ICPMS (127I)

A combination of 19F-NMR spectroscopy, HPLC-MS/MS, HPLC-MS with constant neutral loss scanning of 127, and HPLC-ICPMS with iodine detection has enabled the profiling, quantification, and limited characterization of the metabolites produced in the earthworm Eisenia veneta, following exposure to 2-fluoro-4-iodoaniline. Mass spectrometric analysis of the worm tissue and coelomic fluid afforded the identification of two Phase II metabolites, N-glutamyl and N-glucoside conjugates, indicating the importance of these pathways in the detoxification of xenobiotics for earthworms. Several further metabolites were observed and quantified by 19F-NMR spectroscopy and HPLC-127I-ICPMS, although these were of low abundance and their structures were not unequivocally identified. The parent compound and the glutamyl conjugate were found to be the major xenobiotic components of both the coelomic fluid and the worm tissue, representing approximately 23 and approximately 35%, respectively, of the dose that was recovered from the earthworm tissue extract.