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61 results for “xenobiotic”
Hyper-specialized bamboo lemurs possess a reduced suite of xenobiotic-metabolizing cytochrome P450 genes
<p><span>Subfamilies of cytochrome P450 proteins have been strongly linked to the metabolism of physiologically disruptive compounds such as alkaloids, terpenoids, and other xenobiotics. Consistent with this function, these genes have adaptively evolved in response to environmental pressures exerted on animals, such as herbivores, that consume elevated amounts of toxic xenobiotics or plant secondary metabolites (PSMs). Theory on evolutionary tradeoffs predicts that highly specialized herbivores should exhibit a relatively narrow toolkit of adaptations to accommodate the concomitantly narrow arrays of PSMs in their diets. The bamboo lemurs of Madagascar (genera </span><em>Prolemur</em> and <em>Hapalemur</em>) represent an interesting test case for this theory because of their dietary hyper-specialization, as these lemurs consume bamboo and grasses at rates otherwise unseen in the order Primates. To test whether the hyper-specialized folivory of these primates is reflected in a similarly specialized and narrow P450 gene suite, we assembled a dataset of confidently assembled CYP1-3 genes for two species of bamboo lemur and 13 additional lemur species. With this dataset, we tested the predictions that bamboo lemurs would exhibit, first, greater rates of gene loss for xenobiotic-metabolizing P450s and, second, relaxed selection on xenobiotic-metabolizing P450 subfamilies relative to lemurs without such dietary hyper-specialization. We found support for the prediction of gene loss in the <em>CYP2B,</em> <em>CYP2C</em>, <em>CYP2D</em>, <em>CYP2J</em>, and <em>CYP3A</em> subfamilies, all of which encode xenobiotic metabolizers. We inferred relaxation of selection for the <em>CYP1A</em> and <em>CYP2D</em> subfamilies. The <em>CYP2F</em> subfamily exhibited a signal of significant intensification of selection in the bamboo-lemur lineage. The evolution of the P450 genes in bamboo lemurs provides support for the evolutionary tradeoff hypothesis, and we further hypothesize that, rather than adapting to a general array of PSMs, bamboo lemurs have instead adapted to the primary toxin in their diet, the highly potent poison cyanide.</p>
Hyper-specialized bamboo lemurs possess a reduced suite of xenobiotic-metabolizing cytochrome P450 genes
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Data from: In vivo assessment of respiratory burst inhibition by xenobiotic exposure using larval zebrafish
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Fig. 4. A in Biotransformation of xenobiotics by hairy roots
Fig. 4. A Biotransformation of paracetamol into conjugates of glutathione to form a stable complex during phase II reaction stage B Biotransformation of paracetamol into conjugates of glucoside to form a stable complex which undergoes storage into lignin fraction of cell wall during phase III reaction by HRs of A. rusticana.
Fig. 5 in Biotransformation of xenobiotics by hairy roots
Fig. 5. Biotransformation of oxybenzone into conjugates of glucose and malonyl-glucoside during phase II reaction and further storage of malonyl conjugate in vacuole or cell wall during phase III reaction by HRs of A. rusticana.
Fig. 2 in Biotransformation of xenobiotics by hairy roots
Fig. 2. Biotransformation of phenols by hydroxylation, dehydrogenation, ortho-cleavage and oxidation reactions of Phase I reaction by HRs of H. annuus.
Fig. 7 in Biotransformation of xenobiotics by hairy roots
Fig. 7. Proposed biotransformation stages of TNT (2,4,6-trinitrotoluene) to 4-amino-2,6-dinitrotoluene and 2-amino-4,6-nitrotoluene by HRs of C. roseus.
Fig. 3 in Biotransformation of xenobiotics by hairy roots
Fig. 3. Biotransformation of 2, 4-dichlorophenol into 2-chloro-6-(2,4-dichlorophenoxy)-1,4-benzoquinone by HRs of N. tabacum during phase II reaction.
Fig. 6 in Biotransformation of xenobiotics by hairy roots
Fig. 6. Biotransformation of DDT to DDD, DDE, and DDMU during phase I reaction by HRs of B. juncea and C. intybus.
Fig. 8 in Biotransformation of xenobiotics by hairy roots
Fig. 8. Biotransformation of textile azo dyes: A) Reactive Red 198, B) Acid Red 114 by HRs of T. patula and I. carnea, respectively.
Data from: Natural allelic variations of xenobiotic metabolizing enzymes affect sexual dimorphism in Oryzias latipes
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Data from: Widespread dysregulation of long non-coding genes associated with fatty acid metabolism, cell division, and immune response gene networks in xenobiotic-exposed rat liver
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Data from: Neonatal activation of the xenobiotic-sensors PXR and CAR results in acute and persistent down-regulation of PPARα-signaling in mouse liver
Safety concerns have emerged regarding the potential long-lasting effects due to developmental exposure to xenobiotics. The pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are critical xenobiotic-sensing nuclear receptors that are highly expressed in liver. The goal of this study was to test our hypothesis that neonatal exposure to PXR- or CAR-activators not only acutely but also persistently regulates the expression of drug-processing genes (DPGs). A single dose of the PXR-ligand PCN (75 mg/kg), CAR-ligand TCPOBOP (3 mg/kg), or vehicle (corn oil) was administered intraperitoneally to 3-day-old neonatal wild-type mice. Livers were collected 24 h post-dose or from adult mice at 60 days of age, and global gene expression of these mice was determined using Affymetrix Mouse Transcriptome Assay 1.0. In neonatal liver, PCN up-regulated 464 and down-regulated 449 genes, whereas TCPOBOP up-regulated 308 and down-regulated 112 genes. In adult liver, there were 15 persistently up-regulated and 22 persistently down-regulated genes following neonatal exposure to PCN, as well as 130 persistently up-regulated and 18 persistently down-regulated genes following neonatal exposure to TCPOBOP. Neonatal exposure to both PCN and TCPOBOP persistently down-regulated multiple Cyp4a members, which are prototypical-target genes of the lipid-sensor PPARα, and this correlated with decreased PPARα-binding to the Cyp4a gene loci. RT-qPCR, western blotting, and enzyme activity assays in livers of wild-type, PXR-null, and CAR-null mice confirmed that the persistent down-regulation of Cyp4a was PXR and CAR dependent. In conclusion, neonatal exposure to PXR- and CAR-activators both acutely and persistently regulates critical genes involved in xenobiotic and lipid metabolism in liver.
Data from: Serum-free and xenobiotic-free preservation of cultured human limbal epithelial cells
Aim/Purpose of the Study: To develop a one-week storage method, without serum and xenobiotics, that would maintain cell viability, morphology, and phenotype of cultured human limbal epithelial sheets. Materials and Methods: Human limbal explants were cultured on intact human amniotic membranes for two weeks. The sheets were stored in a hermetically sealed container at 23°C in either a serum-free medium with selected animal serum-derived compounds (Quantum 286) or a xenobiotic-free medium (Minimal Essential Medium) for 4 and 7 days. Stored and non-stored cultures were analyzed for cell viability, amniotic membrane and epithelial sheet thickness, and a panel of immunohistochemical markers for immature cells (ΔNp63α, p63, Bmi-1, C/EBP∂, ABCG2 and K19), differentiated cells (K3 and Cx43), proliferation (PCNA), and apoptosis (Caspase-3). Results: The cell viability of the cultures was 98 ± 1% and remained high after storage. Mean central thickness of non-stored limbal epithelial sheets was 23 ± 3 μm, and no substantial loss of cells was observed after storage. The non-stored epithelial sheets expressed a predominantly immature phenotype with ΔNp63α positivity of more than 3% in 9 of 13 cultures. After storage, the expression of ABCG2 and C/EBP∂ was reduced for the 7 day Quantum 286-storage group; (P = 0.04), and Bmi-1 was reduced after 4 day Quantum 286-storage; (P = 0.02). No other markers varied significantly. The expression of differentiation markers was unrelated to the thickness of the epithelia and amniotic membrane, apart from ABCG2, which correlated negatively with thickness of limbal epithelia (R = -0.69, P = 0.01) and ΔNp63α, which correlated negatively with amniotic membrane thickness (R = -0.59, P = 0.03). Conclusion: Limbal epithelial cells cultured from explants on amniotic membrane can be stored at 23°C in both serum-free and xenobiotic-free media, with sustained cell viability, ultrastructure, and ΔNp63α-positivity after both 4 and 7 days.
Fig. 1 in Biotransformation of xenobiotics by hairy roots
Fig. 1. Proposed approach of biotransformation of xenobiotics in soil and bioreactor systems.
Cryptorchidism: Impact of in Utero Exposure to Xenobiotics With Hormonal Action
ClinicalTrials.gov study NCT00565513. IPD Sharing: Not stated. Countries: 0. Publications: 0.
Data from: Neonatal activation of the xenobiotic-sensors PXR and CAR results in acute and persistent down-regulation of PPARα-signaling in mouse liver
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Data from: Serum-free and xenobiotic-free preservation of cultured human limbal epithelial cells
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Data from: Widespread epigenetic changes to the enhancer landscape of mouse liver induced by a specific xenobiotic agonist ligand of the nuclear receptor CAR
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Data from: Discovery and evaluation of candidate sex-determining genes and xenobiotics in the gonads of lake sturgeon (Acipenser fulvescens)
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International Brain Laboratory public data
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OpenNeuro
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