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1.
Artigo em Inglês | MEDLINE | ID: mdl-36669813

RESUMO

In the present review we addressed the determination of DNA damage induced by small-molecule carcinogens, considered their persistence in DNA and mutagenicity in in vitro and in vivo systems over a period of 30 years. The review spans from the investigation of the role of DNA damage in the cascade of chemical carcinogenesis. In the nineties, this concept evolved into the biomonitoring studies comprising multiple biomarkers that not only reflected DNA/chromosomal damage, but also the potential of the organism for biotransformation/elimination of various xenobiotics. Since first years of the new millennium, dynamic system of DNA repair and host susceptibility factors started to appear in studies and a considerable knowledge has been accumulated on carcinogens and their role in carcinogenesis. It was understood that the final biological links bridging the arising DNA damage and cancer onset remain to be elucidated. In further years the community of scientists learnt that cancer is a multifactorial disease evolving over several decades of individual´s life. Moreover, DNA damage and DNA repair are inseparable players also in treatment of malignant diseases, but affect substantially other processes, such as degeneration. Functional monitoring of DNA repair pathways and DNA damage response may cast some light on above aspects. Very little is currently known about the relationship between telomere homeostasis and DNA damage formation and repair. DNA damage/repair in genomic and mitochondrial DNA and crosstalk between these two entities emerge as a new interesting topic.


Assuntos
Exposição Ocupacional , Xenobióticos , Humanos , Ensaio Cometa , Xenobióticos/toxicidade , Dano ao DNA , Reparo do DNA , Carcinogênese/genética , DNA , Carcinógenos
2.
J Pharm Biomed Anal ; 225: 115224, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36603394

RESUMO

Xiaokeyinshui extract combination (XEC), originating from a traditional Chinese formula Xiaokeyinshui (XKYS) recorded in ancient Bencao, has been reported to exert significant hypoglycemic effects. However, the chemical profiles, metabolic transformation and pharmacokinetic behavior of XEC in vivo were unclear. The research was to investigate the chemical constituents, metabolic profiles and pharmacokinetic behavior of XEC. A UPLC-QE-Orbitrap-HRMS qualification method was developed to identify the chemical constituents in XEC and xenobiotics of XEC in plasma, urine, feces and bile of rats after oral administration. A LC-MS quantification method was established and applied for the pharmacokinetic studies of major active compounds of XEC in normal and T2DM rats and Coptidis Rhizoma extracts (CRE) in T2DM rats. Fifty eight compounds in XEC and a total of 152 xenobiotics were identified in T2DM rats, including 28 prototypes and 124 metabolites. The metabolic pathways were demethylation, demethyleneization, reduction, hydroxylation, hydrolysis and subsequent binding reactions, including glucuronidation, sulfation and methylation. According to the results of chemical constituents and metabolites, 7 ingredients, including berberine, palmatine, coptisine, epiberberine, berberrubine, magnoflorine and aurantio-obtusin were suggested for markers to comparative pharmacokinetics study in normal rats and T2DM rats. Compared with normal rats, the Tmax of berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine was significantly longer. The value of Cmax for palmatine, coptisine, epiberberine and berberrubine was significantly decreased in XEC T2DM group. The value of AUC for alkaloids was higher in diabetic rats. After oral CRE, alkaloids including berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine could be detected in vivo. Compared with T2DM rats after oral administration of CRE, the value of Tmax and Cmax for berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine exhibited significant differences in XEC T2DM group. This research provided an overview of the chemical profiles and metabolic profiling of XEC and elucidated the effect of diabetic state and compatibility on pharmacokinetic behaviors of active components in XEC. This research also can provide the material basis of XEC for subsequent quality control research.


Assuntos
Alcaloides , Berberina , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas , Ratos , Animais , Xenobióticos , Alcaloides/química , Medicamentos de Ervas Chinesas/química
3.
Sci Rep ; 13(1): 276, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609626

RESUMO

Hypertension-related left ventricular hypertrophy is recognized as a good predictor of adverse cardiovascular events. However, the underlying mechanism of left ventricular hypertrophy is still not fully understood. This study employed liquid chromatography coupled with tandem mass spectrometry to investigate global changes in protein profile in myocardium of spontaneously hypertensive rat, a classical animal model of essential hypertension. There were 369 differentially expressed proteins in myocardium between spontaneously hypertensive rats and normotensive rats. Xenobiotic catabolic process, cholesterol binding and mitochondrial proton-transporting ATP synthase were found to be the most significantly enriched biological process, molecular function and cellular component terms of Gene Ontology, respectively. Drug metabolism-cytochrome P450 was revealed to be the most significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways. FYN proto-oncogene, Src family tyrosine kinase was found to have the most interactions with other proteins. Differentially expressed proteins involved in xenobiotic catabolic process, lipid transport and metabolism, mitochondrial function might be targets for further study of hypertension-related left ventricular hypertrophy.


Assuntos
Hipertensão , Hipertrofia Ventricular Esquerda , Ratos , Animais , Ratos Endogâmicos SHR , Proteômica/métodos , Xenobióticos/metabolismo , Ratos Endogâmicos WKY , Miocárdio/metabolismo
4.
Methods Mol Biol ; 2616: 441-451, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36715952

RESUMO

Cigarette smoking is a major prodromal factor for the onset of many adverse health effects that may occur in the short run and is the leading cause of preventable disease, disability, and death in the United States. Moreover, it is well established that chronic smoking is associated with vascular endothelial dysfunction in a causative and dose-dependent manner primarily related to the release of reactive oxygen species (ROS), nicotine, and the induction of oxidative stress (OS)-driven inflammation. Preclinical studies have also shown that nicotine (the principal e-liquid ingredient used in e-cigarettes) can also cause OS, exacerbating cerebral ischemia and secondary brain injury. Likewise, chronic e-Cig vaping could be prodromal to cerebrovascular impairment and promote cerebrovascular conditions favoring stroke onset and worsening post-ischemic brain injury. Therefore, using mouse models is crucial to understand how xenobiotics such as those released by conventional and/or e-cigs can impact the onset and severity of stroke as well as post-stroke recovery. To appropriately model human-like smoking/vaping behavior in mice, however, the exposure to these xenobiotics must be standardized and undertaken in a controlled environment. This chapter describes a well-validated protocol to reproduce standardized chronic tobacco smoke or e-cigarette vape exposure in mice in the setting of a mouse transient ischemic stroke model.


Assuntos
Lesões Encefálicas , Fumar Cigarros , Sistemas Eletrônicos de Liberação de Nicotina , Acidente Vascular Cerebral , Vaping , Camundongos , Humanos , Animais , Nicotina/efeitos adversos , Vaping/efeitos adversos , Fumar Cigarros/efeitos adversos , Xenobióticos , Acidente Vascular Cerebral/etiologia
5.
Int J Mol Sci ; 24(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36674588

RESUMO

Glycogen, the branched polymer of glucose is found mainly in the liver and muscle in mammals. Along with several other proteins, glycogen forms separate cellular organelles, and particles in cells. Glycogen particles in the liver have a special metabolic and also regulatory connection to the intracellular endomembrane system, particularly the endoplasmic reticulum. This connection is part of the organelle homeostasis in hepatocytes and forms a "glycogenoreticular system". The actual size of hepatic glycogen stores and the rate of glycogenolysis determines several essential liver-specific metabolic processes, such as glucose secretion for the maintenance of blood glucose levels or the glucuronidation of certain vital endo-, and xenobiotics, and are also related to liver antioxidant defense. In starvation, and in certain physiological and pathological states, where glycogen stores are depleted, functions of the glycogenoreticular system are altered. The starvation-induced depletion of hepatic glycogen content changes the biotransformation of various endo- and xenobiotics. This can be observed especially in acute DILI (drug-induced liver injury) due to paracetamol overdose, which is the most common cause of acute liver failure in the West.


Assuntos
Glicogênio , Glicogênio Hepático , Animais , Glicogênio/metabolismo , Xenobióticos/metabolismo , Fígado/metabolismo , Glucose/metabolismo , Retículo Endoplasmático/metabolismo , Mamíferos/metabolismo
6.
Ecotoxicol Environ Saf ; 249: 114427, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36516623

RESUMO

Mycotoxins beauvericin (BEA) and enniatin B (ENN B) affect negatively several systems and demand more studies as the mechanisms are still unclear. The simultaneous presence of contaminants in the environment manifests consequences of exposure for both animals and flora. Daphnia magna is considered an ideal invertebrate to detect effects of toxic compounds and environmental alterations. In this study, the potential toxicity and the basic mechanism of BEA and ENN B individually and combined were studied in D. magna. Acute and delayed toxicity were evaluated, and transcript levels of genes involved in xenobiotic metabolism (mox, gst, abcb1, and abcc5), reproduction, and oxidative stress (vtg-SOD) were analyzed by qPCR. Though no acute toxicity was found, results revealed a spinning around and circular profile of swimming, a strong decrease of survival after 72 h for BEA and ENN B at 16 µM and 6.25 µM, respectively, while for BEA + ENN B [8 + 1.6] µM after 96 h. The amount of mycotoxin remaining in the media revealed that the higher the concentration assayed the higher the amount remaining in the media. Differential regulation of genes suggests that xenobiotic metabolism is affected denoting different effects on transcription for tested mycotoxins. The results provide new insights into the underlying risk assessment of BEA and ENN B not only through food for consumers but also for the environment.


Assuntos
Daphnia , Indicadores Ambientais , Micotoxinas , Animais , Daphnia/efeitos dos fármacos , Daphnia/genética , Micotoxinas/toxicidade , Xenobióticos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos
7.
Chemosphere ; 312(Pt 1): 137265, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36403809

RESUMO

Phthalates are extensively used in the production of plastics products and have been verified to induce lung injury. Lycopene (LYC) has proved an effective preventive and can be utilized to prevent phthalates-induced toxicity. However, the role of phthalate in pathogenesis of lung injury remain poorly researched, and little work has been devoted whether LYC could alleviate phthalate-induced lung toxicity via modulating nuclear xenobiotic receptors (NXRs) response. Here, di (2-ethylhexyl) phthalate (DEHP) is used as the representative of phthalates for further studies on toxicity of phthalates and the antagonistic role of LYC in phthalates-induced lung injury. We found that DEHP exposure caused alveoli destruction and alveolar epithelial cells type II damage. Mechanistically, DEHP exposure increased nuclear accumulation of aryl hydrocarbon receptor (AHR) and its downstream genes level, including cytochrome P450-dependent monooxygenase (CYP) 1A1 and CYP1B1. Constitutive androstane receptor (CAR) and their downstream gene level, including CYP2E1 are also increased after phthalates exposure. Significantly, LYC supplementation relieves lung injury from DEHP exposure by inhibiting the activation of NXRs. We confirm that NXRs plays a key role in phthalates-induced lung injury. Our study showed that LYC may have a positive role in alleviating the toxicity effects of phthalates, which provides an effective strategy for revising phthalates-induced injury.


Assuntos
Dietilexilftalato , Lesão Pulmonar , Ácidos Ftálicos , Humanos , Dietilexilftalato/toxicidade , Lesão Pulmonar/induzido quimicamente , Licopeno/farmacologia , Ácidos Ftálicos/toxicidade , Receptores Citoplasmáticos e Nucleares/metabolismo , Xenobióticos/toxicidade , Aminoácidos/metabolismo
8.
Inn Med (Heidelb) ; 64(1): 93-101, 2023 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-36480072

RESUMO

Physicians look at drug-drug interactions (DDI), or more correctly xenobiotic interactions, in an emotional mixture of fear and interest, due to the apparently countless number of adverse drug effects (ADE) that can occur. The interactions as such are seen as errors; however, interactions cannot be avoided and are an inevitable part of the normal work of physicians. The problem is how to recognize interactions and how to handle them. A xenobiotic interaction can often even improve the effectiveness of a pharmacotherapy and minimize the risks. If all examples of what can possibly happen are not necessarily counted, the flood of information becomes relatively manageable. There are only seven different classes of interactions, four pharmacodynamic and three pharmacokinetic interactions. Currently, there are hotlines and both analogue as well as digital databanks to answer questions and address uncertainties, unfortunately of markedly different quality! Aids, such as therapeutic drug monitoring (TDM) supplement these offers. Every pharmacokinetic interaction can be recognized by determination of the concentration of the active agent. The comprehensive clinical pharmacological TDM report explain the information contained in the concentration of the active agent about the individual patient from whom the blood was drawn. All physicians can learn how to compile the clinical pharmacological TDM report by themselves or they can request it in interdisciplinary cooperation via a council. Medical expertise in handling xenobiotic interactions not only opens the door to adaptation of the pharmacotherapy to the needs of the individual patient but also saves huge budget resources for the healthcare system.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Inundações , Humanos , Xenobióticos , Interações Medicamentosas , Monitoramento de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle
9.
J Med Toxicol ; 19(1): 26-36, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36525217

RESUMO

SARS-CoV-2 emerged in 2019 and led to the COVID-19 pandemic. Efforts to develop therapeutics against SARS-Cov-2 led to both new treatments and attempts to repurpose existing medications. Here, we provide a narrative review of the xenobiotics and alternative remedies used or proposed to treat COVID-19. Most repositioned xenobiotics have had neither the feared toxicity nor the anticipated efficacy. Repurposed viral replication inhibitors are not efficacious and frequently associated with nausea, vomiting, and diarrhea. Antiviral medications designed specifically against SARS-CoV-2 may prevent progression to severe disease in at-risk individuals and appear to have a wide therapeutic index. Colloidal silver, zinc, and ivermectin have no demonstrated efficacy. Ivermectin has a wide therapeutic index but is not efficacious and acquiring it from veterinary sources poses additional danger. Chloroquine has a narrow therapeutic index and no efficacy. A companion review covers vaccines, monoclonal antibodies, and immunotherapies. Together, these two reviews form an update to our 2020 review.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Xenobióticos , Pandemias/prevenção & controle , Ivermectina/uso terapêutico , Antivirais/uso terapêutico
10.
Int J Mol Sci ; 23(24)2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36555764

RESUMO

The study of insect adaptation to the defensive metabolites of host plants and various kinds of insecticides in order to acquire resistance is a hot topic in the pest-control field, but the mechanism is still unclear. In our study, we found that a general signal pathway exists in H. armigera which can regulate multiple P450s, GSTs and UGTs genes to help insects decrease their susceptibility to xenobiotics. Knockdown of HaNrf2 and HaAhR expression could significantly increase the toxicity of xenobiotics to H. armigera, and simultaneously decrease the gene expression of P450s, GSTs and UGTs which are related to the xenobiotic metabolism and synthesis of insect hormone pathways. Then, we used EMSA and dual luciferase assay to verify that a crosstalk exists between AhR and Nrf2 to regulate multiple P450s, GSTs and UGTs genes to mediate H. armigera susceptibility to plant allelochemicals and insecticides. The detoxification genes' expression network which can be regulated by Nrf2 and AhR is still unknown, and there were also no reports about the crosstalk between AhR and Nrf2 that exist in insects and can regulate multiple detoxification genes' expression. Our results provide a new general signaling pathway to reveal the adaptive mechanism of insects to xenobiotics and provides further insight into designing effective pest-management strategies to avoid the overuse of insecticides.


Assuntos
Inseticidas , Mariposas , Animais , Inseticidas/farmacologia , Larva/metabolismo , Xenobióticos/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Mariposas/genética , Mariposas/metabolismo , Insetos/metabolismo , Transdução de Sinais
11.
Int J Mol Sci ; 23(23)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36499247

RESUMO

The aryl hydrocarbon receptor (AHR) is a markedly established regulator of a plethora of cellular and molecular processes. Its initial role in the detoxification of xenobiotic compounds has been partially overshadowed by its involvement in homeostatic and organ physiology processes. In fact, the discovery of its ability to bind specific target regulatory sequences has allowed for the understanding of how AHR modulates such processes. Thereby, AHR presents functions in transcriptional regulation, chromatin architecture modifications and participation in different key signaling pathways. Interestingly, such fields of influence end up affecting organ and tissue homeostasis, including regenerative response both to endogenous and exogenous stimuli. Therefore, from classical spheres such as canonical transcriptional regulation in embryonic development, cell migration, differentiation or tumor progression to modern approaches in epigenetics, senescence, immune system or microbiome, this review covers all aspects derived from the balance between regulation/deregulation of AHR and its physio-pathological consequences.


Assuntos
Receptores de Hidrocarboneto Arílico , Transdução de Sinais , Receptores de Hidrocarboneto Arílico/metabolismo , Homeostase , Xenobióticos , Regulação da Expressão Gênica
12.
Yakugaku Zasshi ; 142(11): 1201-1225, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-36328450

RESUMO

ATP-binding cassette (ABC) transporters, which comprise the largest gene-family in humans, are membrane proteins that transport various substrates, depending on ATP hydrolysis. Among these transporters, several include ABCB1 (P-glycoprotein), identified here for the first time in humans, which exports anti-cancer drugs from cancer cells, thus participating in multidrug resistance (MDR). ABC transporters also export drugs, in general, from the human body, therefore affecting overall pharmacokinetics. We have contributed, here, to a better understanding of the role of these exporter proteins in two aspects. First, we have cloned the human ABCC2 gene and identified mutations in hereditary hyperbilirubinemia patients, demonstrating the role of ABCC2 as a xenobiotic export pump. Second, we also found an unexpected role of ABCB1 in cancer, in that it promotes tumor initiation independently of the MDR phenomenon, which was further confirmed by a chemoprevention experiment using verapamil, an ABCB1 inhibitor. In this review, I discuss the role of ABC transporters, both in biodefense against xenobiotics and in cancer development and malignant alterations, based on our results as well as the studies of others.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Neoplasias , Humanos , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Resistência a Múltiplos Medicamentos/genética , Neoplasias/genética , Neoplasias/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Xenobióticos , Trifosfato de Adenosina , Resistencia a Medicamentos Antineoplásicos/genética
13.
Oxid Med Cell Longev ; 2022: 4640161, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388166

RESUMO

The liver is a highly metabolic organ and plays a crucial role in the transportation, storage, and/or detoxication of xenobiotics. Liver damage induced by xenobiotics (e.g., heavy metal, endocrine disrupting chemicals, Chinese herbal medicine, or nanoparticles) has become a pivotal reason for liver diseases, leading to great clinical challenge and much attention for the past decades. Given that endoplasmic reticulum (ER) is the prominent organelle involved in hepatic metabolism, ER dysfunction, namely, ER stress, is clearly observed in various liver diseases. In response to ER stress, a conserved adaptive signaling pathway known as unfolded protein response (UPR) is activated to restore ER homeostasis. However, the prolonged ER stress with UPR eventually leads to the death of hepatocytes, which is a pathogenic event in many hepatic diseases. Therefore, analyzing the perturbation in the activation or inhibition of ER stress and the UPR signaling pathway is likely an effective marker for investigating the molecular mechanisms behind the toxic effects of xenobiotics on the liver. We review the role of ER stress in hepatic diseases and xenobiotic-induced hepatotoxicity, which not only provides a theoretical basis for further understanding the pathogenesis of liver diseases and the mechanisms of hepatotoxicity induced by xenobiotics but also presents a potential target for the prevention and treatment of xenobiotic-related liver diseases.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Hepatopatias , Humanos , Xenobióticos/toxicidade , Estresse do Retículo Endoplasmático/fisiologia , Hepatopatias/etiologia , Resposta a Proteínas não Dobradas
14.
Environ Toxicol Pharmacol ; 96: 104012, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36372389

RESUMO

As a plasticizer, di-2-ethylhexyl phthalate (DEHP) has been listed as a potential endocrine disruptor by The World Health Organization. The toxicity of DEHP has been widely studied, but its toxicity on the digestive tract of birds has not been clarified. Female quail were treated by gavage with DEHP (250, 500, 750 mg/kg), with the blank and vehicle control groups reserved. The result showed that DEHP raised the damage severity grade, and decreased the ratio of villus length to crypt depth. The content and activity of cytochrome P450 system (CYP450s) were increased by DEHP. DEHP interfered with the transcription of nuclear xenobiotic receptors (NXRs), CYP isoforms, and the nuclear factor-E2-related factor 2 (Nrf2) signaling pathway. This study revealed DEHP could cause the imbalance in CYP450s mediated by NXRs, and then promote Nrf2 mediated antioxidant defense. This study provided new evidence about the mechanisms of DEHP-induced toxic effects on digestive tract.


Assuntos
Coturnix , Dietilexilftalato , Animais , Feminino , Coturnix/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Codorniz/metabolismo , Dietilexilftalato/toxicidade , Xenobióticos , Jejuno/metabolismo , Receptores Citoplasmáticos e Nucleares , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo
15.
BMC Genomics ; 23(1): 757, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36396986

RESUMO

BACKGROUND: Hemiptera is one of the most speciose orders of insects, and the most speciose considering Hemimetabola. Through their evolutive history, hemipterans with different feeding habits have adapted to deal with different chemical challenges. Three major gene families are involved in xenobiotic detoxification in insects: the cytochromes P450 (CYPs), carboxyl/cholinesterases (CCEs), and glutathione transferases (GSTs). Here we perform a comparative analysis on the complement of these gene superfamilies across five hemipteran species; four heteropterans (the pentatomid plant feeders Nezara viridula and Halyomorpha halys; the hematophagous Cimex lectularius, Cimicidae, and Rhodnius prolixus, Reduviidae), and one Auchenorrhyncha plant feeder (Nilaparvata lugens). RESULTS: Our results point to an expansion of several enzyme families associated with xenobiotic detoxification in heteropterans with respect to other species and the existence of a dynamic evolution pattern including CYP3 clan, hormone and pheromone processing class in the CCE superfamily, and sigma class in GST superfamily. Other detoxification-related families are reduced in the hemipteran species analyzed here: reduction or even absence of epsilon class and reduced delta class in GST superfamily; absence of mitochondrial CYP12 family; absence of CYP9 family in CYP3 clan; and reduction or even absence of some dietary/detoxification groups of CCEs. Interestingly, the most polyphagous species analyzed here (H. halys) is also the one that presents the largest repertoire of detoxification enzymes. Gene cluster analysis suggests that this could be due to gene duplication events. CONCLUSIONS: The evolutionary analysis performed here reveals characteristics that are both common and particular for heteropterans. The composition and organization of detoxification-related gene families could shed light on evolutionary forces that shaped their divergence. These families are important for both the detoxification of diet products and for conferring tolerance or resistance to synthetic insecticides. Furthermore, we present the first comprehensive analysis of detoxification gene superfamilies in N. viridula, an understudied species in spite of its economic relevance as a crop pest. The information obtained is of interest for basic insect science as well as for the control of harmful species and the management of insecticide resistance.


Assuntos
Heterópteros , Inseticidas , Rhodnius , Animais , Xenobióticos , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Glutationa Transferase/genética
16.
J Agric Food Chem ; 70(45): 14386-14394, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36331925

RESUMO

Efficient characterization of xenobiotic metabolites and their dynamics in a changing complex matrix remains difficult. Herein, we proposed a time-series-dependent global data filtering strategy for the rapid and comprehensive characterization of xenobiotic metabolites and their dynamic variation based on metabolome data. A set of data preprocessing methods was used to screen potential xenobiotic metabolites, considering the differences between the treated and control groups and the fluctuations over time. To further identify metabolites of the target, an in-house accurate mass database was constructed by potential metabolic pathways and applied. Taking the extract of Ginkgo biloba (EGB) co-incubated with gut microbiota as an example, 107 compounds were identified as flavonoid-derived metabolites (including 67 original from EGB and 40 new) from 7468 ions. Their temporal metabolic profiles and regularities were also investigated. This study provided a systematic and feasible method to elucidate and profile xenobiotic metabolism.


Assuntos
Microbioma Gastrointestinal , Ginkgo biloba , Ginkgo biloba/metabolismo , Flavonoides/metabolismo , Xenobióticos , Extratos Vegetais/metabolismo , Biotransformação
17.
Int J Mol Sci ; 23(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36361709

RESUMO

Variation of gut microbiota in metabolic diseases seems to be related to dysbiosis induced by exposure to multiple substances called Microbiota Disrupting Chemicals (MDCs), which are present as environmental and dietary contaminants. Some recent studies have focused on elucidating the alterations of gut microbiota taxa and their metabolites as a consequence of xenobiotic exposures to find possible key targets involved in the severity of the host disease triggered. Compilation of data supporting the triad of xenobiotic-microbiota-metabolic diseases would subsequently allow such health misbalances to be prevented or treated by identifying beneficial microbe taxa that could be Next Generation Probiotics (NGPs) with metabolic enzymes for MDC neutralisation and mitigation strategies. In this review, we aim to compile the available information and reports focused on variations of the main gut microbiota taxa in metabolic diseases associated with xenobiotic exposure and related microbial metabolite profiles impacting the host health status. We performed an extensive literature search using SCOPUS, Web of Science, and PubMed databases. The data retrieval and thorough analyses highlight the need for more combined metagenomic and metabolomic studies revealing signatures for xenobiotics and triggered metabolic diseases. Moreover, metabolome and microbiome compositional taxa analyses allow further exploration of how to target beneficial NGP candidates according to their alleged variability abundance and potential therapeutic significance. Furthermore, this holistic approach has identified limitations and the need of future directions to expand and integrate key knowledge to design appropriate clinical and interventional studies with NGPs. Apart from human health, the beneficial microbes and metabolites identified could also be proposed for various applications under One Health, such as probiotics for animals, plants and environmental bioremediation.


Assuntos
Microbioma Gastrointestinal , Microbiota , Probióticos , Animais , Humanos , Disbiose/terapia , Xenobióticos , Probióticos/uso terapêutico
18.
Nutrients ; 14(19)2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36235732

RESUMO

In an in vivo rat model of human exposure to cadmium (Cd; 5 and 50 mg/L, 6 months), whether the supplementation with zinc (Zn; 30 and 60 mg/L, increasing its daily intake by 79% and 151%, respectively) protects against the unfavourable impact of this xenobiotic on the vascular tissue of the abdominal aorta was investigated. The treatment with Cd led to oxidative stress and increased the concentrations of pro-inflammatory interleukin 1ß (IL-1ß), total cholesterol (TC), triglycerides (TG), and endothelial nitric oxide synthase (eNOS) and decreased the concentration of anti-inflammatory interleukin 10 (IL-10) in the vascular tissue. Cd decreased the expression of intercellular adhesion molecule-1 (ICAM-1), platelet endothelial cell adhesion molecule-1 (PECAM-1), and L-selectin on the endothelial cells. The administration of Zn prevented most of the Cd-induced alterations or at least weakened them (except for the expression of adhesive molecules). In conclusion, Zn supplementation may protect from the toxic impact of Cd on the blood vessels and thus exert a beneficial influence on the cardiovascular system. The increase in the intake of Zn by 79% may be sufficient to provide this protection and the effect is related to the antioxidative, anti-inflammatory, and antiatherogenic properties of this essential element.


Assuntos
Aorta Abdominal , Cádmio , Zinco , Animais , Aorta Abdominal/efeitos dos fármacos , Cádmio/toxicidade , Colesterol/metabolismo , Suplementos Nutricionais , Células Endoteliais/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Selectina L/metabolismo , Modelos Teóricos , Óxido Nítrico Sintase Tipo III/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Ratos , Ratos Wistar , Triglicerídeos/metabolismo , Xenobióticos/toxicidade , Zinco/farmacologia
19.
Int J Mol Sci ; 23(20)2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36293398

RESUMO

Adipose stem cells (ASCs) are reported to play a role in normal physiology as well as in inflammation and disease. The objective of this work was to elucidate inter-individual differences in growth, gene expression and response to inflammatory stimuli in ASCs from different donors. Human ASC1 (male donor) and ASC2 (female donor) were purchased from Lonza (Walkersville, MD). Cell proliferation was determined by the sulforhodamine B assay. After time-dependent treatment of ASCs with or without bacterial lipopolysaccharide (LPS), marker gene mRNAs for proliferation, steroid hormones, and xenobiotic and immune pathways were determined using RT-PCR, and secreted cytokine levels in media were measured using the Bio-Plex cytokine assay kit. ASCs from both donors expressed androgen receptors but not estrogen receptors. ASC2 had a 2-fold higher proliferation rate and a 6-fold higher level of proliferation marker Ki67 mRNA than ASC1. ASC2 exhibited significantly greater fold induction of TNF-α and CCL2 by LPS compared to ASC1. TNF-α and GM-CSF protein levels were also significantly higher in the LPS-induced ASC2 media, but IL-6 secretion was higher in the LPS-induced ASC1 media. Our findings suggest that inter-individual variability and/or possible sex differences exist in ASCs, which may serve as a key determinant to inflammatory responses of ASCs.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos , Lipopolissacarídeos , Feminino , Masculino , Humanos , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Receptores Androgênicos/metabolismo , Xenobióticos/metabolismo , Tecido Adiposo/metabolismo , Proliferação de Células , RNA Mensageiro/metabolismo , Citocinas/genética , Citocinas/metabolismo , Hormônios/metabolismo , Expressão Gênica
20.
J Toxicol Sci ; 47(10): 421-428, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36184561

RESUMO

Acetaminophen (APAP) and p-aminophenol (p-AP) are the analogous simple phenolic compounds that undergo sulfate conjugation (sulfation) by cytosolic sulfotransferases. Sulfation is generally thought to lead to the inactivation and disposal of endogenous as well as xenobiotic compounds. This study aimed to investigate the antioxidative effects of O-sulfated form of APAP and p-AP, i.e., APAPS and p-APS, in comparison with their unsulfated counterparts. Using a 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay, the antioxidant capacity of APAPS was shown to be approximately 126-times lower than that of APAP. In contrast, p-APS displayed comparable activity as unsulfated p-AP. Similar trends concerning the suppressive effects of these chemicals on cellular O2- radical generation were found using an activated granulocytic neutrophil cell model. Collectively, these results indicated that, depending on the presence of an additional "active site", sulfation may not always decrease the antioxidant activities of phenolic compounds.


Assuntos
Acetaminofen , Sulfatos , Aminofenóis , Antioxidantes/farmacologia , Fenóis , Sulfotransferases , Xenobióticos
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