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1.
J Environ Pathol Toxicol Oncol ; 39(3): 201-212, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865912

RESUMO

Acute and chronic effects of ultraviolet radiation (UVR) on human health have long been a concern. It is well known that acute UVR causes epidermal hyperplasia, erythema, delayed tanning, pigment darkening, and free-radical formation. Apart from acute effects of UVR, its chronic effects involve immunosuppression, photoaging, exacerbation, photodermatoses, and photocarcinogenesis. To protect skin from harmful effects of UVR, UV filters were developed. But these may cause harmful effects in humans and on the environment; adverse effects of these chemicals have been evaluated for > 20 yr. Studies show that UV filters may lead to endocrine disruption, hepatotoxicity, mutagenicity, and systemic toxicity. Literature on environmental effects of UV filters suggests that they are bioaccumulative, pseudopersistent, and possibly toxic to aquatic ecosystems. The objective of this review is to summarize toxic effects and safety concerns of organic UV filters on human beings and the environment. We focus on UV filters' organic endocrine-disrupting effects by reviewing both in vivo and in vitro studies.


Assuntos
Disruptores Endócrinos/toxicidade , Compostos Orgânicos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Protetores Solares/toxicidade , Animais , Biotransformação , Disruptores Endócrinos/química , Disruptores Endócrinos/farmacocinética , Humanos , Estrutura Molecular , Compostos Orgânicos/química , Compostos Orgânicos/farmacocinética , Protetores Solares/química , Protetores Solares/farmacocinética
2.
Science ; 369(6507)2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32855308

RESUMO

Microbial consortia are a promising alternative to monocultures of genetically modified microorganisms for complex biotransformations. We developed a versatile consortium-based strategy for the direct conversion of lignocellulose to short-chain fatty acids, which included the funneling of the lignocellulosic carbohydrates to lactate as a central intermediate in engineered food chains. A spatial niche enabled in situ cellulolytic enzyme production by an aerobic fungus next to facultative anaerobic lactic acid bacteria and the product-forming anaerobes. Clostridium tyrobutyricum, Veillonella criceti, or Megasphaera elsdenii were integrated into the lactate platform to produce 196 kilograms of butyric acid per metric ton of beechwood. The lactate platform demonstrates the benefits of mixed cultures, such as their modularity and their ability to convert complex substrates into valuable biochemicals.


Assuntos
Clostridium tyrobutyricum/metabolismo , Ácidos Graxos Voláteis/biossíntese , Lignina/metabolismo , Megasphaera elsdenii/metabolismo , Consórcios Microbianos , Veillonella/metabolismo , Biotransformação , Ácido Láctico/metabolismo
3.
Bioresour Technol ; 316: 123910, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32750640

RESUMO

The present study investigated the bacterial community, metabolome and biotransformation of phenolic compounds in sainfoin silage inoculated either with or without Lactobacillus plantarum. Our results revealed that the epiphytic microbiota of wilted sainfoin mainly comprised Acinetobacter, Spingomonas, Pseudomonas, Lactobacillus, Delftia and Aquabacterium. After ensiling, L. acetotolerans, L. buchneri, L. plantarum, L. pentosus and Clostridium tyrobutricum were the dominant species. Compared to the control, the inoculant L. plantarum increased the relative abundance of L. buchneri while decreased that of the other dominant species. The ensiling process increased the concentrations of 21 flavones, 16 flavonols, 16 flavonoids, 14 flavanones and 9 isoflavones while decreased other 32 flavones and 11 anthocyanins, which mainly modulated by the "isoflavonoid biosynthesis" and "flavonoid biosynthesis" pathways. The inoculant L. plantarum mainly reduced the concentrations of 10 flavones. Compared with the control, the inoculant L. plantarum mainly affected the metabolism pathways related to carbohydrates and nitrogen.


Assuntos
Lactobacillus plantarum , Microbiota , Biotransformação , Fermentação , Metaboloma , Silagem/análise , Zea mays
4.
Sci Total Environ ; 747: 141144, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-32777496

RESUMO

Safety and environmental behavior of bisphenol A (BPA) alternatives have attracted considerable attention because of their wide use. In the present study, toxicity and biotransformation of bisphenol S (BPS), a primary alternative to BPA, in Chlorella vulgaris were investigated. BPS had a significant inhibition on the growth rate of C. vulgaris with an inhibition rate of 41.6%, 103.7% and 238.4% under exposure of 1, 10 and 100 mg L-1 BPS, respectively. BPS (2 d EC50: 3.16 mg L-1) had a higher acute toxicity to C. vulgaris than BPA (2 d EC50: 41.43 mg L-1), but its toxicity was gradually lower than BPA as the exposure time increased. BPS underwent rapid degradation and was more recalcitrant to degradation by C. vulgaris than BPA at 5 and 10 mg L-1. BPS was less accumulated in algal cells than BPA (p < 0.05), suggesting that it may pose less risk than BPA on the aquatic algophagous organisms and other high-trophic-level predators through the food chain. In addition, six new metabolites of BPS were identified in algal cells using high-resolution mass spectrometry. This is the first time that degradation pathway for BPS in algae is described, and these results represent a significant advance in understanding the fate of BPS and other BPA substitutes in the aquatic environment.


Assuntos
Chlorella vulgaris , Compostos Benzidrílicos/análise , Compostos Benzidrílicos/toxicidade , Biotransformação , Água Doce , Fenóis , Sulfonas
5.
Sci Total Environ ; 746: 141020, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32750576

RESUMO

Carbon nanomaterials (CNs), which gain heightened attention as novel materials, are increasingly incorporated into daily products and thus are released into the environment. Limited research on CNs environmental fates lags their industry growth, only few bacteria have been confirmed to biotransform CNs and the mechanism behind has not been revealed yet. In this study, four types of commercial CNs, i.e. graphene oxide (GO), reduced graphene oxide (RGO), single walled carbon nanotubes (SWCNTs), and oxidized (carboxylated) SWCNTs, were selected for investigation. The biotransformation of CNs by Labrys sp. WJW, which could grow with these CNs as the sole carbon source, was investigated. The bacterial transformation was proved by qPCR, transmission electron microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, liquid chromatography/time-of-flight/mass spectrometry, and gas chromatograph-mass spectrometry analyses. The biotransformation resulted in morphology change, defect increase and functional group change of these CNs. Furthermore, the underlying mechanism of CNs biodegradation mediated by extracellular Fenton-like reaction was demonstrated. In this reaction, the OH production was mediated by reduction of H2O2 involved a continuous cycle of Fe(II)/Fe(III). These findings reveal a novel degradation mechanism of microorganism towards high molecular weight substrate, which will provide a new insight into the environmental fate of CNs and the guidance for their safer use.


Assuntos
Nanoestruturas , Nanotubos de Carbono , Biotransformação , Compostos Férricos , Peróxido de Hidrogênio
6.
Chemosphere ; 260: 127532, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32683017

RESUMO

Acetaminophen (APAP), a widely used analgesic-antipyretic drug, is frequently detected in the environment and may pose ecological risks to aquatic communities. In this work, an APAP-degrading organism, designated as Ensifer sp. POKHU, was isolated from activated sludge (AS) enriched with APAP. POKHU degraded up to 630 mg/L of APAP without substrate inhibition. The bacterium metabolized APAP to hydroquinone (HQ) via 4-aminophenol (4-AP). APAP derivatives, 4AP, HQ, and 1,4-benzoquinone (BQ), frequently detected in the environment, were found to inhibit nitrogen metabolism (ammonium oxidation) to a greater extent than APAP. POKHU had the ability to degrade varying levels (0.4-40 mg/L) of 4-AP, HQ, and BQ, which indicated a great potential for detoxification in environments contaminated with both APAP and its derivatives. The addition of POKHU to fresh AS samples taken from a wastewater treatment plant greatly increased the biotransformation rates of APAP from 5.6 d-1 (no POKHU augmentation) to >20.0 d-1 (5% POKHU). Bioaugmentation with POKHU reduced 400 µg/L of APAP to levels below its ecotoxicity threshold within 4 h, which is shorter than the typical hydraulic retention times for full-scale AS processing. Overall, this study identified a new auxiliary biological agent for APAP detoxification, which could degrade both APAP and its metabolic derivatives (those that can be more toxic than the parent contaminant, APAP). The results have practical implications for developing a biological means (detoxification and bioaugmentation) of treating high-strength pharmaceutical waste streams, such as wastewater from hospitals and drug manufactures, and of landfill leachates.


Assuntos
Acetaminofen/metabolismo , Biodegradação Ambiental , Rhizobiaceae/isolamento & purificação , Esgotos/microbiologia , Purificação da Água/métodos , Acetaminofen/análogos & derivados , Acetaminofen/química , Analgésicos não Entorpecentes/metabolismo , Biotransformação , Hidroquinonas/metabolismo , Cinética , Rhizobiaceae/metabolismo , Águas Residuárias/química , Poluentes Químicos da Água/química
7.
Sci Total Environ ; 744: 140652, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-32693271

RESUMO

Due to their wide-distribution, high-biocompatibility and low-cost, nature-derived quinone redox mediators (NDQRM) have shown great potential in bioremediation through mediating electron transfers between microorganisms and between microorganisms and contaminants in anaerobic biotransformation processes. It is obvious that their performance in bioremediation was limited by the availability of quinone-based groups in NDQRM. A sustainable solution is to enhance the electron transfer capacity and retention capacity by the modification of NDQRM. Therefore, this review comprehensively summarized the modification techniques of NDQRM according to their multiple roles in anaerobic biotransformation systems. In addition, their potential applications in greenhouse gas mitigation, contaminant degradation in anaerobic digestion, contaminant bioelectrochemical remediation and energy recovery were discussed. And the problems that need to be addressed in the future were pointed out. The obtained knowledge would promote the exploration of novel NDQRM, and provide suggestions for the design of anaerobic consortia in biotransformation systems.


Assuntos
Quinonas , Anaerobiose , Biodegradação Ambiental , Biotransformação , Oxirredução
8.
Elife ; 92020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32639233

RESUMO

Hydroxychloroquine and chloroquine are used extensively in malaria and rheumatological conditions, and now in COVID-19 prevention and treatment. Although generally safe they are potentially lethal in overdose. In-vitro data suggest that high concentrations and thus high doses are needed for COVID-19 infections, but as yet there is no convincing evidence of clinical efficacy. Bayesian regression models were fitted to survival outcomes and electrocardiograph QRS durations from 302 prospectively studied French patients who had taken intentional chloroquine overdoses, of whom 33 died (11%), and 16 healthy volunteers who took 620 mg base chloroquine single doses. Whole blood concentrations of 13.5 µmol/L (95% credible interval 10.1-17.7) were associated with 1% mortality. Prolongation of ventricular depolarization is concentration-dependent with a QRS duration >150 msec independently highly predictive of mortality in chloroquine self-poisoning. Pharmacokinetic modeling predicts that most high dose regimens trialled in COVID-19 are unlikely to cause serious cardiovascular toxicity.


Assuntos
Cloroquina/envenenamento , Overdose de Drogas/mortalidade , Tentativa de Suicídio , Suicídio , Adulto , Antimaláricos/administração & dosagem , Antimaláricos/envenenamento , Antimaláricos/uso terapêutico , Biotransformação , Cloroquina/administração & dosagem , Cloroquina/efeitos adversos , Cloroquina/análogos & derivados , Cloroquina/sangue , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Relação Dose-Resposta a Droga , Reposicionamento de Medicamentos , Eletrocardiografia , Feminino , Cardiopatias/induzido quimicamente , Cardiopatias/mortalidade , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/envenenamento , Hidroxicloroquina/uso terapêutico , Síndrome do QT Longo/induzido quimicamente , Malária/tratamento farmacológico , Masculino , Pandemias , Pneumonia Viral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Medição de Risco
9.
Chem Biol Interact ; 328: 109192, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32712081

RESUMO

Many natural products are prodrugs which are biotransformed and activated after oral administration. The investigation of gastrointestinal and hepatic biotransformation can be facilitated by in vitro screening methods. This study compares two widely used in vitro models for hepatic biotransformation: 1) human S9 fractions and 2) human liver microsomes and cytosolic fractions in a two-step sequence, with the purpose of identifying differences in the biotransformation of medicagenic acid, the putative precursor of active metabolites, responsible for the medicinal effects of the herb Herniaria hirsuta. The combination of liquid chromatography coupled to high-resolution mass spectrometry with subsequent suspect and non-target data analysis allowed the identification of thirteen biotransformation products, four of which are reported here for the first time. Eight biotransformation products resulting from oxidative Phase I reactions were identified. Phase II conjugation reactions resulted in the formation of three glucuronidated and two sulfated biotransformation products. No major differences could be observed between incubations with human liver S9 or when utilizing human microsomal and cytosolic fractions. Apart from two metabolites, both methods rendered the same qualitative metabolic profile, with minor quantitative differences. As a result, both protocols applied in this study can be used to study in vitro human liver biotransformation reactions.


Assuntos
Microssomos Hepáticos/metabolismo , Triterpenos/metabolismo , Biotransformação , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Masculino , Frações Subcelulares/metabolismo , Fatores de Tempo , Triterpenos/química
10.
Toxicol Lett ; 332: 7-13, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32615244

RESUMO

Root canal sealers are commonly used to endodontically treat teeth with periapical infections. Some root canal sealers based on epoxy resin contain bisphenol A diglycidyl ether (BADGE) and bisphenol F diglycidyl ether (BFDGE). The presence of these chemicals is of concern due to the close contact to the blood stream at the apex and the long setting times of up to 24 h. These chemicals, or any of their degradation products or metabolites, can then exert their toxic effects before being excreted. This study aimed to identify the phase I in vitro biotransformation products of BADGE and BFDGE using human liver microsomes. During incubation with microsomal fractions, the epoxides were rapidly hydrolysed in a NADPH independent manner resulting in the formation of BADGE.2H2O and BFDGE.2H2O. Further, oxidative reactions, such as hydroxylation and carboxylation, generated other BADGE metabolites, such as BADGE.2H2O-OH and BADGE.H2O.COOH, respectively. For BFDGE, further oxidation of BFDGE.2H2O led to the newly reported carboxylic acid, BFDGE.H2O.COOH. In total, three specific metabolites have been identified which can serve in future human biomonitoring studies of BADGE and BFDGE.


Assuntos
Compostos Benzidrílicos/farmacocinética , Compostos de Epóxi/farmacocinética , Fígado/metabolismo , Materiais Restauradores do Canal Radicular/farmacocinética , Compostos Benzidrílicos/toxicidade , Biotransformação , Ácidos Carboxílicos/metabolismo , Compostos de Epóxi/toxicidade , Feminino , Humanos , Hidroxilação , Masculino , Microssomos Hepáticos/metabolismo , NADP/metabolismo , Oxirredução , Materiais Restauradores do Canal Radicular/toxicidade
11.
Toxicol Lett ; 332: 107-117, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32615245

RESUMO

The aim of this study was to assess phthalate exposure of non-occupationally exposed working aged population in Finland. Studied phthalates included diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), diisobutyl phthalate (DiBP), benzyl butyl phthalate (BzBP), dicyclohexyl phthalate (DCHP), di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DiNP), diisodecyl phthalate (DiDP), di(2-propylheptyl) phthalate (DPHP), and di-n-octyl phthalate (DnOP). Sample collection campaign took place in 2015. Metabolites of DEP, DnBP and DiBP were detected in all the first morning void urine samples of the non-occupationally exposed volunteers (n = 60; 42 women and 18 men; aged 25-63). Metabolite of BBP and secondary metabolites of DEHP and DiNP were detected in >90% of the samples. MCHP (1.7%), MEHP (18.3%), cx-MiNP (8.3%) and MnOP (1.7%) were less frequently detected. MiNP and OH-MPHP were not detected in any of the urine samples. The observed levels were mostly comparable to the levels published in the adult population in Europe and the US. One notable difference was the observed higher exposure of the Finnish study population to DnBP in comparison to the German, Austrian, Norwegian and US populations. The levels of individual phthalates did not often correlate very well with each other. In most cases, higher exposure to phthalates was seen in females in comparison to males, which is in accordance with other studies. The urinary levels were compared to the biomonitoring equivalents (BEs), which were calculated on the basis of published DNELs (derived no-effect levels). The P95 levels of individual phthalates remained below the respective BEs, the highest risk characterization ratio (RCR) being 0.88 for DnBP and the second highest 0.34 for DiBP. For other phthalates, the RCRs were below 0.2. Using the P95 levels, combined exposure to DnBP, DiBP, DEHP and BBP resulted in risk characterization ratio exceeding 1. This suggests a need to limit the exposure to these phthalates.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/urina , Ácidos Ftálicos/urina , Adulto , Monitoramento Biológico , Biotransformação , Monitoramento Ambiental , Poluentes Ambientais/efeitos adversos , Feminino , Finlândia , Humanos , Masculino , Pessoa de Meia-Idade , Ácidos Ftálicos/efeitos adversos , Medição de Risco , Caracteres Sexuais
12.
Aquat Toxicol ; 226: 105565, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32682195

RESUMO

Pyrene (PYR) and fluorene (FLU) are among the sixteen priority Polycyclic Aromatic Hydrocarbons (PAH) of the United States Environmental Protection Agency and are both frequently detected in contaminated sites. Due to the importance of bivalve mollusks in biomonitoring programs and the scarce information on the biotransformation system in these organisms, the aim of this study was to investigate the effect of PYR and FLU at the transcriptional level and the enzymatic activities of some biotransformation systems in the Pacific oyster Crassostrea gigas, and to evaluate the histological effects in their soft tissues. Oysters C. gigas were exposed for 24 h and 96 h to PYR (0.25 and 0.5 µM) and FLU (0.6 and 1.2 µM). After exposure, transcript levels of cytochrome P450 coding genes (CYP1-like, CYP2-like, CYP2AU2, CYP356A1, CYP17α-like), glutathione S tranferase genes (omega GSTO-like and microsomal, MGST-like) and sulfotransferase gene (SULT-like), and the activity of ethoxyresorufin O-deethylase (EROD), Glutathione S-transferase (GST) and microssomal GST (MGST) were evaluated in gills. Histologic changes were also evaluated after the exposure period. PYR and FLU bioconcentrated in oyster soft tissues. The half-life time of PYR in water was lower than fluorene, which is in accordance to the higher lipophilicity and bioconcentration of the former. EROD activity was below the limit of detection in all oysters exposed for 96 h to PYR and FLU. The reproductive stage of the oysters exposed to PYR was post-spawn. Exposure to PYR caused tubular atrophy in digestive diverticula, but had no effect on transcript levels of biotransformation genes. However, the organisms exposed for 96 h to PYR 0.5 µM showed higher MGST activity, suggesting a protective role against oxidative stress in gills of oysters under higher levels of PYR in the tissues. Increased number of mucous cells in mantle were observed in oysters exposed to the higher FLU concentration, suggesting a defense mechanisms. Oysters exposed for 24 h to FLU 1.2 µM were in the ripe stage of gonadal development and showed higher transcript levels of CYP2AU2, GSTO-like and SULT-like genes, suggesting a role in the FLU biotransformation. In addition, after 96 h of exposure to FLU there was a significant increase of mucous cells in the mantle of oysters but no effect was observed on the EROD, total GST and MGST activities. These results suggest that PAH have different effects on transcript levels of biotransformation genes and enzyme activities, however these differences could also be related to the reproductive stage.


Assuntos
Crassostrea/efeitos dos fármacos , Fluorenos/toxicidade , Pirenos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Biotransformação/efeitos dos fármacos , Crassostrea/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Fluorenos/metabolismo , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Glutationa Transferase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pirenos/metabolismo , Poluentes Químicos da Água/metabolismo
13.
Chemosphere ; 260: 127515, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32682130

RESUMO

In this work we present an assessment of mercury (Hg) and methyl mercury (MeHg) bioaccumulation in different species of marine sponges collected off the Northwestern Mediterranean and Northeastern Atlantic coasts. Overall the results showed significant accumulation of Hg in sponges, with the Mediterranean sponge Chondrilla nucula exhibiting the highest total Hg content (up to 0.5 mg kg-1) and bio-concentration factor (BCF) up to 23. A significant inter-species variability of Hg bioaccumulation was observed among species collected at the same site. The sponges, collected in marine environment contaminated with Hg show consistently higher Hg accumulation, meaning that the bioaccumulation is proportional to the Hg availability in the surrounding environment. Different extraction protocols were tested for MeHg analysis and, generally, a low MeHg ratio in Hg species (4% and 17% average for Mediterranean and Irish sponges respectively) was detected suggesting a possible demethylation process and therefore a promising role of sponges for Hg bioremediation Additionally, the Hg isotopic composition in these organisms was determined and it showed that MDF (mass dependent fractionation) is the main process in sponges, with the absence of significant MIF. This result suggests a dominant role of associated microbial population in the methylation and/or demethylation processes.


Assuntos
Bioacumulação , Monitoramento Ambiental/métodos , Mercúrio/análise , Compostos de Metilmercúrio/análise , Poríferos/metabolismo , Poluentes Químicos da Água/análise , Animais , Oceano Atlântico , Biotransformação , Fracionamento Químico , Mar Mediterrâneo , Mercúrio/metabolismo , Compostos de Metilmercúrio/metabolismo , Especificidade da Espécie , Poluentes Químicos da Água/metabolismo
14.
Tohoku J Exp Med ; 251(2): 87-90, 2020 06.
Artigo em Inglês | MEDLINE | ID: covidwho-593619

RESUMO

In light of the recent pandemic, favipiravir (Avigan®), a purine nucleic acid analog and antiviral agent approved for use in influenza in Japan, is being studied for the treatment of coronavirus disease 2019 (COVID-19). Increase in blood uric acid level is a frequent side effect of favipiravir. Here, we discussed the mechanism of blood uric acid elevation during favipiravir treatment. Favipiravir is metabolized to an inactive metabolite M1 by aldehyde oxidase and xanthine oxidase, and excreted into urine. In the kidney, uric acid handling is regulated by the balance of reabsorption and tubular secretion in the proximal tubules. Favipiravir and M1 act as moderate inhibitors of organic anion transporter 1 and 3 (OAT1 and OAT3), which are involved in uric acid excretion in the kidney. In addition, M1 enhances uric acid reuptake via urate transporter 1 (URAT1) in the renal proximal tubules. Thus, favipiravir is thought to decrease uric acid excretion into urine, resulting in elevation of uric acid levels in blood. Elevated uric acid levels were returned to normal after discontinuation of favipiravir, and favipiravir is not used for long periods of time for the treatment of viral infection. Thus, the effect on blood uric acid levels was subclinical in most studies. Nevertheless, the adverse effect of favipiravir might be clinically important in patients with a history of gout, hyperuricemia, kidney function impairment (in which blood concentration of M1 increases), and where there is concomitant use of other drugs affecting blood uric acid elevation.


Assuntos
Amidas/efeitos adversos , Antivirais/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Hiperuricemia/induzido quimicamente , Pneumonia Viral/tratamento farmacológico , Pirazinas/efeitos adversos , Ácido Úrico/sangue , Aldeído Oxidase/metabolismo , Amidas/farmacocinética , Amidas/urina , Antivirais/farmacocinética , Biotransformação , Interações Medicamentosas , Humanos , Hiperuricemia/fisiopatologia , Rim/metabolismo , Nefropatias/metabolismo , Estrutura Molecular , Proteína 1 Transportadora de Ânions Orgânicos/antagonistas & inibidores , Transportadores de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos Sódio-Independentes/antagonistas & inibidores , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Pandemias , Pirazinas/farmacocinética , Pirazinas/urina , Xantina Oxidase/metabolismo
15.
Ecotoxicol Environ Saf ; 202: 110859, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32574861

RESUMO

The effects of quinoid compounds on azo dyes decolorization were studied. Compared with other quinones, menadione was the most effective at aiding azo dye decolorization. Sodium formate was a suitable carbon source for the anaerobic decolorization system. Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis indicated that the microbial structure changed in response to varying carbon sources. Phylogenetic analysis showed that the anaerobic sludge was consisted mainly of nine genera. The mechanism studies showed that the biotransformation of menadione to its hydroquinone form was the rate-limiting step in the dye decolorization process. Moreover, study of the electron transfer mechanism of quinone-mediated reduction showed that azo dye decolorization is not a specific reaction. The NADH chain was involved in the decolorization process. The methane production test indicated that azo dyes had an inhibitory effect on methane production. However, supplementation with a redox mediator could recover the inhibited methanogenesis. High-throughput sequencing analysis revealed that the methanogenic archaeal community was altered in the anaerobic sludge with or without azo dyes and the redox mediator.


Assuntos
Compostos Azo/metabolismo , Quinonas/metabolismo , Eliminação de Resíduos Líquidos , Anaerobiose , Compostos Azo/química , Benzoquinonas , Biotransformação , Catálise , Corantes/química , Metano/metabolismo , Oxirredução , Filogenia , Quinonas/química , Esgotos
16.
Aquat Toxicol ; 225: 105540, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32569997

RESUMO

The zebrafish (Danio rerio) embryo has increasingly been used as an alternative model in human and environmental toxicology. Since the cytochrome P450 (CYP) system is of fundamental importance for the understanding and correct interpretation of the outcome of toxicological studies, constitutive and xenobiotic-induced 7-methoxycoumarin-O-demethylase (MCOD), i.e. 'mammalian CYP2-like', activities were monitored in vivo in zebrafish embryos via confocal laser scanning microscopy. In order to elucidate molecular mechanisms underlying the MCOD induction, dose-dependent effects of the prototypical CYP inducers ß-naphthoflavone (aryl hydrocarbon receptor (AhR) agonist), rifampicin (pregnane X receptor (PXR) agonist), carbamazepine and phenobarbital (constitutive androstane receptor (CAR) agonists) were analyzed in zebrafish embryos of varying age. Starting from 36 h of age, all embryonic stages of zebrafish could be shown to have constitutive MCOD activity, albeit with spatial variation and at distinct levels. Whereas carbamazepine, phenobarbital and rifampicin had no effect on in vivo MCOD activity in 96 h old zebrafish embryos, the model aryl hydrocarbon receptor agonist ß-naphthoflavone significantly induced MCOD activity in 96 h old zebrafish embryos at 46-734 nM, however, without a clear concentration-effect relationship. Induction of MCOD activity by ß-naphthoflavone gradually decreased with progression of embryonic development. By in vivo characterization of constitutive and xenobiotic-induced MCOD activity patterns in 36, 60, 84 and 108 h old zebrafish embryos, this decrease could primarily be attributed to an age-related decline in the induction of MCOD activity in the cardiovascular system. Results of this study provide novel insights into the mechanism and extent, by which specific CYP activities in early life-stages of zebrafish can be influenced by exposure to xenobiotics. The study thus lends further support to the view that zebrafish embryos- at least from an age of 36 h - have an elaborate and inducible biotransformation system.


Assuntos
Sistema Enzimático do Citocromo P-450/biossíntese , Embrião não Mamífero/efeitos dos fármacos , Oxirredutases O-Desmetilantes/biossíntese , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Animais , Biotransformação , Indutores das Enzimas do Citocromo P-450/toxicidade , Embrião não Mamífero/enzimologia , Desenvolvimento Embrionário/efeitos dos fármacos , Receptores de Hidrocarboneto Arílico/metabolismo , Xenobióticos/toxicidade , Proteínas de Peixe-Zebra/metabolismo , beta-Naftoflavona/toxicidade
17.
Phytochemistry ; 176: 112421, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32505862

RESUMO

The exponential industrial growth we see today rides on the back of large scale production of chemicals, explosives and pharmaceutical products. However, the effluents getting released from their manufacturing units are greatly compromising the sustainability of our environment. With greater awareness of the imperative for environmental clean-up, a promising approach that is attracting increasing research interests is biodegradation of xenobiotics. In this approach, biotransformation has proven to be one of the most effective tools. While many different model frameworks have been used to study different aspects of biotransformation, hairy roots (HRs) have been found to be exceptionally valuable. HR cultures are preferred over other in-vitro model systems due to their biochemical stability and hormone-autotrophy. In addition, the multi-enzyme biosynthetic potential of HRs which is similar to the parent plant and their relatively low-cost cultural requirements further characterize their suitability for biotransformation. The recent progress observed in scale-up of HR cultures and understanding of functional genomics has opened up new dimensions providing valuable insights for industrial application. This review article summarizes the potential of HR cultures in the biotransformation of xenobiotics, their limitations in the application on a large scale and current strategies to alleviate them. Advancement in bioreactors engineering enabling large scale cultivation and modern gene technologies improving biotransformation efficiency promises to extend laboratory results to industrial applications.


Assuntos
Raízes de Plantas , Xenobióticos , Biodegradação Ambiental , Reatores Biológicos , Biotransformação
18.
Environ Pollut ; 265(Pt B): 114838, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32563804

RESUMO

Characteristics and transformation of organic phosphorus in water are vital to biogeochemical cycling of phosphorus and support of blooms of phytoplankton and cyanobacteria. Using solution 31P nuclear magnetic resonance (NMR), combined with field surveys and lab analyses, composition and structural characteristics of dissolved phosphorus (DP), particulate phosphorus (PP) and organic P in algae were studied in two eutrophic lakes in China, Tai Lake and Chao Lake. Factors influencing migration and transformation of these constituents in lake ecosystems were also investigated. A method was developed to extract, flocculate and concentrate DP and PP from lake water samples. Results showed that orthophosphate (Ortho-P) constituted 32.4%-81.3% of DP and 43.7%-54.9% of PP, respectively; while monoester phosphorus (Mono-P) was 13.2%-54.0% of DP and 32.9%-43.7% of PP, respectively. Phosphorus in algae was mostly organic P, especially Mono-P, which was ≥50% of TP. Environmental factors and water quality parameters such as temperature (T), electrical conductivity (EC), pH, secchi depth (SD), dissolved oxygen (DO), chemical oxygen demand (CODcr), chlorophyll-a (Chl-a), affected the absolute and relative concentrations of various P components in the two lakes. Increased temperature promoted bioavailable P (Ortho-P and Mono-P) release to the lake waters. The results can provide an important theoretical basis for the mutual conversion process of organic P components between various media in the lake water environment.


Assuntos
Lagos , Fósforo/análise , Biotransformação , China , Ecossistema , Monitoramento Ambiental , Eutrofização
19.
Ecotoxicol Environ Saf ; 201: 110797, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32505760

RESUMO

Microalgae play an important role in arsenic (As) bioaccumulation and biogeochemical cycling in marine ecosystems. Marine microalgal growth and As biotransformation processes depend on environmental factors, including salinity, temperature, and nutrient concentrations, and data in this regard are available in the literature. However, research on the integrated effects of environmental factors on marine diatom species remains scarce and unclear. Herein, salinity and temperature are both considered in combination to investigate their influence on As uptake, biotransformation, and photosynthetic efficiency (PE). Two strains of marine diatom species, Asteroplanus karianus and Skeletonema sp., were cultured in an f/2-based nutrient medium. Microalgae were cultured under various temperatures (5.0, 20, and 35 °C) and salinities (1.0‰, 10‰, 25‰, and 40‰) in association with As and phosphate-enriched (1.0 µmol L-1 of As(V) + 10 µmol L-1 of PO43-) or deficient (20 nmol L-1 of As(V) + 1.0 µmol L-1 of PO43-) conditions. For both species, maximum growth, As accumulation, biotransformation, and PE were recorded at 10 and 14 day of culture. Microalgal growth, As accumulation, biotransformation, and PE were maximum at 20 °C with salinities of 10‰ and 20‰. Cell shape was also observed to be good at optimal at this temperature (20 °C) and range of salinity (10‰ and 20‰). A conceptual model of integrated effects of environmental factors on growth and As accumulation and biotransformation activities by these marine microalgae has been proposed. This study contributed to the elucidation of the relationship between environmental factors and As biotransformation mechanisms, which may further provide significant insight about As remediation processes.


Assuntos
Organismos Aquáticos/efeitos dos fármacos , Arseniatos/toxicidade , Microalgas/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Água do Mar/química , Poluentes Químicos da Água/toxicidade , Organismos Aquáticos/metabolismo , Arseniatos/metabolismo , Transporte Biológico , Biotransformação , Ecossistema , Microalgas/metabolismo , Salinidade , Temperatura , Poluentes Químicos da Água/metabolismo
20.
Food Chem ; 331: 127363, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32590269

RESUMO

Rhubarb is a popular food in Europe with laxative properties attributed to anthraquinones. Long term usage of rhubarb anthraquinones has been linked to colonic toxicity, including the formation of melanosis coli, which is associated with increased risk of colon cancer. The major purgative anthraquinone in rhubarb is thought to be sennoside A, which is metabolised by colonic microflora. Here, we sought to identify the toxic metabolite responsible for melanosis coli in rats dosed with rhubarb anthraquinones for up to 90 days. Three metabolites were detected in rat faeces using HPLC. Of these, rhein was identified as the metabolite that accumulated most over time. Fecal flora from treated rats were capable of greater biotransformation of sennoside A to rhein compared to that from control rats. Cell culture experiments suggested that apoptosis and autophagy induced by rhein is the likely mechanism of chronic toxicity of rhubarb anthraquinones.


Assuntos
Antraquinonas/farmacocinética , Antraquinonas/toxicidade , Rheum/química , Animais , Antraquinonas/metabolismo , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Biotransformação , Catárticos/química , Catárticos/farmacologia , Cromatografia Líquida de Alta Pressão , Colo/efeitos dos fármacos , Colo/patologia , Diarreia/induzido quimicamente , Fezes/química , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Células HT29 , Humanos , Laxantes/farmacocinética , Laxantes/toxicidade , Masculino , Ratos Sprague-Dawley , Senosídeos/farmacocinética , Senosídeos/toxicidade
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