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1.
Bull Environ Contam Toxicol ; 105(2): 255-260, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32632463

RESUMO

The present study investigated the biochemical toxicity and potential detoxification mechanisms in earthworms Eisenia fetida exposed to sulfamethazine (SMZ) (7.5, 15 and 30 mg kg-1) either alone or in combination with Copper (Cu) (100 mg kg-1) in soil. The results showed that increasing concentrations of SMZ in soil activated superoxide dismutase, catalase and glutathione peroxidase isozymes, suggesting reactive oxygen species (ROS) burst in earthworms. Treatment with SMZ and Cu separately or in combination caused protein oxidation and damage, elevating the synthesis of ubiquitin, the 20S proteasome, cytochrome P450 (CYP450), and heat shock protein 70 (HSP70). Such treatments also induced the activities of proteases, endoproteinase (EP) and glutathione S-transferases (GSTs). The results suggested that the ubiquitin-20S proteasome, proteases, EP and HSP70 were involved in degradation or remediation of oxidatively damaged proteins. Elevated levels of CYP450 and GSTs also participated in the detoxification of the earthworms.


Assuntos
Cobre/toxicidade , Oligoquetos/efeitos dos fármacos , Poluentes do Solo/toxicidade , Solo/química , Sulfametazina/toxicidade , Animais , Biodegradação Ambiental , Catalase/metabolismo , China , Cobre/metabolismo , Glutationa Peroxidase/metabolismo , Oligoquetos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Poluentes do Solo/metabolismo , Sulfametazina/metabolismo , Superóxido Dismutase/metabolismo
2.
Life Sci ; 257: 118072, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32659367

RESUMO

AIMS: Sunitinib (Su), a tyrosine kinase inhibitor, is one of the most commonly used anti-angiogenic drugs. Some studies have described retinal detachment and photoreceptor damage following systemic exposure to Su, despite beneficial effects achieved with local treatment of ocular pathologies. The aim of this study was to explore the role of NADPH oxidase system and oxidative stress in eyes from Su-treated animals. MAIN METHODS: Male Wistar rats were administered 25 mg Su/kg body weight/day incorporated in the chow for 3 weeks. Upon treatment completion, NADPH oxidase activity and ROS levels were measured in ocular tissue by chemiluminescence and dihydroethidium (DHE) staining, respectively. The expression of NADPH oxidase isoforms (NOX1, NOX2 and NOX4), antioxidant enzymes and endothelial/inducible nitric oxidase isoforms (eNOS/iNOS) in the eyecup and/or retina were measured via immunofluorescence, immunoblotting and RT-qPCR. KEY FINDINGS: NADPH oxidase activity/expression increased in eyecup and retinas from Su-treated rats. Immunohistofluorescence studies in retinal layer confirmed a higher signal of NADPH oxidase isoforms after Su treatment. Treated animals also presented with reductions in NO levels and eNOS expression, whereas iNOS was upregulated. Finally, a significant depletion of antioxidant enzyme glutathione peroxidase was measured in eyecups of rats following Su exposure, and the opposite pattern was seen for glutathione reductase and superoxide dismutase. SIGNIFICANCE: This study demonstrates that Su treatment is associated with NADPH oxidase-derived oxidative stress in the eye. Long-term treatment of Su should be properly monitored to avoid retinotoxic effects that might result in ocular pathologies and sight-threatening conditions.


Assuntos
Estresse Oxidativo/efeitos dos fármacos , Inibidores de Proteínas Quinases/toxicidade , Retina/efeitos dos fármacos , Sunitinibe/toxicidade , Animais , Antioxidantes/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Masculino , NADPH Oxidases/metabolismo , Ratos , Ratos Wistar , Retina/patologia , Superóxido Dismutase/metabolismo
3.
Int J Nanomedicine ; 15: 4191-4203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606672

RESUMO

Purpose: To characterize the nanoparticle of antroquinonol from A. cinnamomea and its ameliorative effects on the reproductive dysfunction in the diabetic male rat. Material and Methods: The chitosan-silicate nanoparticle was used as the carrier for the delivery of antroquinonol from solid-state-cultured A. cinnamomea extract (AC). The rats were fed with a high-fat diet and intraperitoneally injected with streptozotocin to induce diabetes. The rats were daily oral gavage by water [Diabetes (DM) and Control groups], three different doses of chitosan-silicate nanoparticle of antroquinonol from solid-state-cultured A. cinnamomea (nano-SAC, NAC): (DM+NAC1x, 4 mg/kg of body weight; DM+NAC2x, 8 mg/kg; and DM+NAC5x, 20 mg/kg), solid-state-cultured AC (DM+AC5x, 20 mg/kg), or metformin (DM+Met, 200 mg/kg) for 7 weeks. Results: The nano-SAC size was 37.68±5.91 nm, the zeta potential was 4.13±0.49 mV, encapsulation efficiency was 79.29±0.77%, and loading capacity was 32.45±0.02%. The nano-SAC can improve diabetes-induced reproductive dysfunction by regulating glucose, insulin, and oxidative enzyme and by increasing the level of testosterone, follicle-stimulating hormone, luteinizing hormone, and sperm count as well as sperm mobility. In testicular histopathology, the seminiferous tubules of A. cinnamomea-supplemented diabetic rats showed similar morphology with the control group. Conclusion: The nanoparticle of antroquinonol from Antrodia cinnamomea can be used as an effective strategy to improve diabetes-induced testicular dysfunction.


Assuntos
Antrodia/química , Diabetes Mellitus Experimental/tratamento farmacológico , Nanopartículas/química , Reprodução , Ubiquinona/análogos & derivados , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Jejum/sangue , Glutationa Peroxidase/metabolismo , Humanos , Insulina/efeitos adversos , Insulina/sangue , Rim/efeitos dos fármacos , Rim/fisiopatologia , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Estreptozocina , Superóxido Dismutase/metabolismo , Testículo/efeitos dos fármacos , Testículo/patologia , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico
4.
Int J Nanomedicine ; 15: 4501-4521, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606691

RESUMO

Purpose: Elevation of blood homocysteine (Hcy) level (hyperhomocysteinemia) is a risk factor for cardiovascular disorders and is closely associated with endothelial dysfunction. The present study aims to investigate the protective effect and underlying mechanism of nanoscale selenium (Nano-Se) in Hcy-mediated vascular endothelial cell dysfunction in vitro and in vivo. Materials and Methods: By incubating vascular endothelial cells with exogenous Hcy and generating hyperhomocysteinemic rat model, the effects of Nano-Se on hyperhomocysteinemia-mediated endothelial dysfunction and its essential mechanisms were investigated. Results: Nano-Se inhibited Hcy-induced mitochondrial oxidative damage and apoptosis by preventing the downregulation of glutathione peroxidase enzyme 1 and 4 (GPX1, GPX4) in the vascular endothelial cells, thus effectively prevented the vascular damage in vitro and in vivo in the hyperhomocysteinemic rats. Nano-Se possessed similar protective effects but lower toxicity against Hcy in vascular endothelial cells when compared with other forms of Se. Conclusion: The application of Nano-Se could serve as a novel promising strategy against Hcy-mediated vascular dysfunction with reduced risk of Se toxicity.


Assuntos
Antioxidantes/farmacologia , Células Endoteliais da Veia Umbilical Humana/patologia , Hiper-Homocisteinemia/tratamento farmacológico , Hiper-Homocisteinemia/fisiopatologia , Nanopartículas/uso terapêutico , Selênio/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Disponibilidade Biológica , Glutationa Peroxidase/metabolismo , Homocisteína , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Hiper-Homocisteinemia/complicações , Hipertensão/complicações , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Nanopartículas/ultraestrutura , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Selênio/farmacologia
5.
Ecotoxicol Environ Saf ; 203: 111008, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32678766

RESUMO

Glutathione peroxidases (Gpxs) play vital roles in elimination of hydroperoxide and other reactive oxygen species through catalyzing reduced glutathione to protect from oxidative stress caused by heavy metals such as lead. Among the family of Gpxs, Gpx3 is the only extracellular enzyme synthesized in the kidney and actively secreted into the plasma. This study investigated mechanisms of lead-induced GPx3 inactivation both at the animal and molecular levels. Six-week-old mice were randomly divided into 4 groups, and exposed to different lead concentrations (0, 1, 2 and 4 g/L) in their drinking water for 4 weeks. Contents of GPx3 in blood serum were tested by enzyme-linked immunosorbent assay (ELISA) and the mRNA levels of Gpx3 in mice nephrocytes were determined by quantitative real-time PCR (qPCR), both of which showed significantly inhibited at higher lead concentrations accompanied by the decreased Gpx3 activities and the elevated levels of malondialdehyde (MDA) in nephrocytes, which indicated that lead could induce strongly oxidative stress through affecting Gpx3 function. So we further investigated molecular mechanisms of GPx3 inactivation caused by lead with multiple spectroscopic techniques, isothermal titration calorimetry (ITC) and molecular docking studies in vitro. Results showed that lead statically quenched GPx3 fluorescence by tightly binding to the structural domain of GPx3 in a 3:1 ratio with high binding affinity (K = 3.1(±0.087) × 107 mol-1). Further investigation of the conformation of GPx3 by UV-visible spectroscopy and circular dichroism (CD) spectroscopy indicated that lead changed the secondary structure of GPx3 by loosening the GPx3 skeleton and decreasing the hydrophobicity around tryptophan residues. This work proved in vivo and in vitro experiments that lead could induce oxidative stress in mice nephrocytes by interacting with GPx3.


Assuntos
Glutationa Peroxidase/metabolismo , Rim/efeitos dos fármacos , Chumbo/toxicidade , Poluentes da Água/toxicidade , Animais , Glutationa Peroxidase/química , Rim/metabolismo , Rim/patologia , Chumbo/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Ligação Proteica , Estrutura Secundária de Proteína , Selênio/metabolismo , Poluentes da Água/metabolismo
6.
Aquat Toxicol ; 226: 105554, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32653664

RESUMO

The NF-E2-related factor 2 (Nrf2), an ubiquitous, evolutionarily conserved transcription factor, acts as a major sensor of oxidative stress in cells. In the present study, a Nrf2 homolog was newly identified in the thick shell mussel Mytilus coruscus. Accordingly, its functional role in antioxidant defense in response to acute benzo(a)pyrene (Bap) exposure was assessed. The newly identified McNrf2 affiliated to traditional Nrf2 family through Blast, multiple alignment and phylogenetic analysis. After acute exposure to Bap, antioxidants including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathine reductase (GR) were significantly induced in gills and digestive glands at both mRNA and enzymatic levels, and the expression of McNrf2 mRNA was also up-regulated. The analysis of correlating the expression of McNrf2 and the mRNA levels of these antioxidant genes showed positive ties, indicating that Nrf2 was needed for protracted induction of such genes. Further, the recombinant McNrf2 was produced through pET-32a prokaryotic system. After 50 µg/L Bap exposure, ROS generation and LPO level in gills of Nrf2 over-expressed mussels significantly decreased compared to Nrf2 wild-type mussels, as well as reduced ROS production in digestive glands. Collectively, these results show that Nrf2 pathway can provide protection from oxidative stress triggered by Bap in the thick shell mussel.


Assuntos
Antioxidantes/metabolismo , Benzo(a)pireno/toxicidade , Mytilus/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Catalase/metabolismo , Sistema Digestório/efeitos dos fármacos , Sistema Digestório/metabolismo , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Glutationa Peroxidase/metabolismo , Mytilus/metabolismo , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/genética , Filogenia , Superóxido Dismutase/metabolismo
7.
PLoS One ; 15(7): e0236507, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730281

RESUMO

In air-breathing fish a reduction of gill surface area reduces the danger of losing oxygen taken up in the air-breathing organ (ABO) to hypoxic water, but it also reduces the surface area available for ion exchange, so that ion regulation may at least in part be transferred to other organs, like the kidney or the gut. In the air-breathing Arapaima gigas, gill lamellae regress as development proceeds, and starting as a water-breathing embryo Arapaima turns into an obligate air-breathing fish with proceeding development, suggesting that ion regulation is shifted away from the gills as the fish grows. In Arapaima the kidney projects medially into the ABO and thus, probably a unique situation among fishes, is in close contact to the gas of the ABO. We therefore hypothesized that the kidney would be predestined to adopt an increased importance for ion homeostasis, because the elevated ATP turnover connected to ion transport can easily be met by aerobic metabolism based on the excellent oxygen supply directly from the ABO. We also hypothesized that in gill tissue the reduced ion regulatory activity should result in a reduced metabolic activity. High metabolic activity and exposure to high oxygen tensions are connected to the production of reactive oxygen species (ROS), therefore the tissues exposed to these conditions should have a high ROS defense capacity. Using in vitro studies, we assessed metabolic activity and ROS production of gill, kidney and ABO tissue, and determined the activity of ROS degrading enzymes in small (~ 5g, 2-3 weeks old) and larger (~ 670 g, 3-4 months old) A. gigas. Comparing the three tissues revealed that kidney tissue oxygen uptake by far exceeded the uptake measured in gill tissue or ABO. ROS production was particularly high in gill tissue, and all three tissues had a high capacity to degrade ROS. Gill tissue was characterized by high activities of enzymes involved in the glutathione pathway to degrade ROS. By contrast, the tissues of the ABO and in particular the kidney were characterized by high catalase activities, revealing different, tissue-specific strategies in ROS defense in this species. Overall the differences in the activity of cells taken from small and larger fish were not as pronounced as expected, while at the tissue level the metabolic activity of kidney cells by far exceeded the activity of ABO and gill cells.


Assuntos
Peixes/fisiologia , Consumo de Oxigênio/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Brasil , Catalase/metabolismo , Brânquias/enzimologia , Brânquias/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Rim/metabolismo , Mitocôndrias/metabolismo , Superóxido Dismutase/metabolismo
8.
Ecotoxicol Environ Saf ; 202: 110892, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32593098

RESUMO

Carbon nanotubes presence in the environment increases every year because of exponential industrial production around the world. In aquatic environments, carbon nanotubes can interact with other pollutants based on their adsorbent surface chemistry properties. Heavy metal ions represent one of the biggest concerns in water resources nowadays due to anthropogenic activities, in which cadmium (Cd) is one of the most harmful metal for aquatic organisms. This study investigated the influence of two co-exposure protocols differing by the order of interaction of oxidized multiwalled carbon nanotubes (ox-MWCNT) with Cd in zebrafish liver cell line (ZFL). The ox-MWCNT was characterized, Cd content in culture medium and uptake by cells were quantified using ICP-MS and, the reactive oxygen species (ROS), the biotransformation enzymes activity of phase I and II as well as the antioxidants defenses and oxidative damage were analyzed. The effects on the cell cycle were investigated by flow cytometry and DNA damage by comet assay. The exposure to ox-MWCNT alone decreased the activity of catalase, glutathione peroxidase, and glutathione S-transferase and altered the cell cycle with a reduction of cells in the G2/M phase. Cd exposure alone decreased the activity of catalase and glutathione S-transferase, increased ROS, metallothionein, and lipid peroxidation content and causes genotoxicity in the cells. Despite different incubation protocol, the co-exposure ox-MWCNT-Cd increased the Cd content in ZFL cells after 24 h exposure, increased ROS production and DNA damage without differences between them. Our results showed the modulation of ox-MWCNT on Cd effects and contributed to future co-exposure toxicity investigations and nanosafety regulations involving carbon nanomaterials and aquatic pollutants.


Assuntos
Cádmio/toxicidade , Nanotubos de Carbono/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Ciclo Celular , Linhagem Celular , Ensaio Cometa , Dano ao DNA , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Metais Pesados/farmacologia , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Testes de Toxicidade , Peixe-Zebra/metabolismo
9.
Ecotoxicol Environ Saf ; 201: 110861, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32544748

RESUMO

Marine biota have been co-challenged with ocean warming and mercury (Hg) pollution over many generations because of human activities; however, the molecular mechanisms to explain their combined effects are not well understood. In this study, a marine planktonic copepod Pseudodiaptomus annandalei was acutely exposed to different temperature (22 and 25 °C) and Hg (0 and 118 µg/L) treatments in a 24-h cross-factored experiment. Hg accumulation and its subcellular fractions were determined in the copepods after exposure. The expression of the genes of superoxide dismutase (SOD), glutathione peroxidase (GPx), metallothionein1 (mt1), heat shock protein 70 (hsp70), hsp90, hexokinase (hk), and pyruvate kinase (pk) was also analyzed. Both the Hg treatment alone and the combined exposure of warmer temperature plus Hg pollution remarkably facilitated Hg bioaccumulation in the exposed copepods. Compared with the Hg treatment alone, the combined exposure increased total Hg accumulation and also the amount of Hg stored in the metal-sensitive fractions (MSF), suggesting elevated Hg toxicity in P. annandalei under a warmer environment, given that the MSF is directly related to metal toxicity. The warmer temperature significantly up-regulated the mRNA levels of mt1, hsp70, hsp90, and hk, indicating the copepods suffered from thermal stress. With exposure to Hg, the mRNA level of SOD increased strikingly but the transcript levels of hsp90, hk, and pk decreased significantly, indicating that Hg induced toxic events (e.g., oxidative damage and energy depletion). Particularly, in contrast to the Hg treatment alone, the combined exposure significantly down-regulated the mRNA levels of SOD and GPx but up-regulated the mRNA levels of mt1, hsp70, hsp90, hk, and pk. Collectively, the results of this study indicate that ocean warming will potentially boost Hg toxicity in the marine copepod P. annandalei, which is information that will increase the accuracy of the projections of marine ecosystem responses to the joint effects of climate change stressors and metal pollution on the future ocean.


Assuntos
Copépodes/efeitos dos fármacos , Temperatura Alta , Mercúrio/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Copépodes/genética , Copépodes/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Hexoquinase/genética , Hexoquinase/metabolismo , Mercúrio/farmacocinética , Metalotioneína/genética , Metalotioneína/metabolismo , Piruvato Quinase/genética , Piruvato Quinase/metabolismo , RNA Mensageiro/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Regulação para Cima , Poluentes Químicos da Água/farmacocinética
11.
Aquat Toxicol ; 225: 105528, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32569996

RESUMO

Abamectin (ABM) has been extensively used in Chinese aquaculture systems for parasite control, but no information is available regarding its effects on the important freshwater commercial fish species Schizothorax prenanti. We performed an acute toxicity test to determine the effects of ABM on S. prenanti, and the 48- and 96-h median lethal concentration values were 33.32 and 15.98 µg/L, respectively. In a second test, animals were exposed to sublethal concentrations of ABM (0.5, 2 or 8 µg/L) for 8 days, and various cytological and biochemical parameters were measured. ABM caused DNA damage in hepatocytes, with significant increases in Olive Tail Moment values and 8-hydroxy-2'-deoxyguanosine levels. Hepatocytic apoptosis occurred following all treatments, and was accompanied by an increase in reactive oxygen species (ROS) generation and caspase activity in a dose- and time-dependent manner. In addition, there were significant decreases in glutathione peroxidase levels and superoxide dismutase and catalase activity and increases in malonaldehyde levels. ABM-induced hepatocytic apoptosis in S. prenanti was probably triggered by ROS generation following a cascade reaction of caspases in mitochondrial or death receptor pathways, which caused antioxidant inhibition, oxidative product accumulation, and DNA damage in the liver.


Assuntos
Cyprinidae/metabolismo , Dano ao DNA , Ivermectina/análogos & derivados , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Cyprinidae/genética , Cyprinidae/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Água Doce/química , Glutationa Peroxidase/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Ivermectina/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Malondialdeído/metabolismo , Oxirredução , Superóxido Dismutase/metabolismo
12.
Aquat Toxicol ; 225: 105527, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32599436

RESUMO

A diverse range of chemicals are used in agriculture to increase food production on a large scale, and among them is the use of pesticides such as chlorothalonil, a broad-spectrum fungicide used in the control of foliar fungal diseases. This study aimed to elucidate the effects of chlorothalonil on biochemical biomarkers of oxidative stress in tissues of the fish Danio rerio. To achieve this, animals were exposed for 4 and 7 days, to nominal concentrations of chlorothalonil at 0 µg/L (DMSO, 0.001%), 0.1 µg/L and 10 µg/L, and after the exposure period, the tissues (gills and liver) were removed for biochemical analysis. Antioxidant capacity against peroxyl radicals (ACAP) and enzyme activities, such as superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) and glutamate cysteine ligase (GCL), were evaluated in both tissues. In addition, the concentration of reactive oxygen species (ROS), reduced glutathione (GSH) and lipid peroxidation (LPO) levels were also analysed. A significant increase in ROS concentration, ACAP levels, GST and GCL activities and a significant reduction of LPO levels in gills exposed to the highest concentration were observed after 4 days. However, there was a significant reduction of ACAP and CAT activity, as well as a significant increase of GST activity and LPO levels in gills exposed to the lower concentration after 7 days. The liver was less affected, presenting a significant reduction in CAT activity and LPO levels after 4 days. However, a significant increase in SOD activity and LPO levels occurred after 7 days. These results indicate that chlorothalonil, after 4 days, caused activation of the antioxidant defence system in gills of animals exposed to the highest concentration. However, after 7 days, the lowest concentration of this compound caused oxidative stress in this same organ. Also, the results show that gills were more affected than the liver, probably because gills can be involved in chlorothalonil metabolisation. Therefore, it is possible that the liver could be exposed to lower chlorothalonil concentrations or less toxic metabolites due to the metabolism taking place in the gills.


Assuntos
Antioxidantes/metabolismo , Fungicidas Industriais/toxicidade , Nitrilos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Animais , Catalase/metabolismo , Brânquias/efeitos dos fármacos , Brânquias/enzimologia , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Peróxidos/metabolismo , Superóxido Dismutase/metabolismo
13.
Toxicon ; 184: 152-157, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32531289

RESUMO

Aflatoxicosis is one of the threats that cause severe mortalities in fish farms. The dietary functional additives are a friendly approach attributed to beneficial effects on aquatic animals. The study aimed at evaluating the impact of Spirulina platensis (SP) on the biochemical indices and antioxidative function of Nile tilapia (Oreochromis niloticus) intoxicated with aflatoxin B1 (AFB1). A control diet and 3 test diets were enriched with 0% SP/0 mg AFB1/kg (control), 1% SP (SP), 2.5 mg AFB1/kg diet (AFB1), and 1% SP+2.5 mg AFB1/kg diet (SP/AFB1). The diets were supplied to three aquaria for each group twice daily at the rate of 2.5% for 30 days. The blood alanine transaminase (ALT), alkaline phosphatase (ALP), and aspartate transaminase (AST) were significantly increased by AFB1 toxicity with regards to fish fed the control and SP diets (P < 0.05). The inclusion of SP in the diet of tilapia intoxicated with AFB1 lowered the levels of ALT, AST, and ALP in comparison to fish contaminated with AFB1 without SP (P < 0.05). The total blood protein and albumin were decreased in fish contaminated with AFB1 (P < 0.05); however, the dietary SP resulted in improving the blood protein and albumin with similar levels with the control and SP diets. The urea and creatinine were increased in tilapia fed AFB1 diet without SP (P < 0.05); however, the inclusion of SP reduced the levels of urea and creatinine with similar levels with the control and SP diets. The antioxidative capacity of Nile tilapia fed SP and contaminated with AFB1 is expressed by superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) concentration. The activities of SOD and GSH were decreased by AFB1 (P < 0.05); however, dietary SP increased the SOD and GSH in fish fed AFB1. On the other hand, the concentration of MDA was increased in tilapia fed AFB1 (P < 0.05); however, SP decreased the level of MDA in fish fed AFB1. In conclusion, the application of SP in the aquafeed seems to be an innovative approach to relieve the toxic influences of AFB1 on aquatic animals.


Assuntos
Aflatoxina B1/toxicidade , Ciclídeos/fisiologia , Venenos/toxicidade , Spirulina/fisiologia , Alanina Transaminase/metabolismo , Ração Animal , Animais , Antioxidantes/metabolismo , Aspartato Aminotransferases/metabolismo , Catalase/metabolismo , Creatinina/metabolismo , Dieta , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Malondialdeído/metabolismo , Estresse Oxidativo , Superóxido Dismutase/metabolismo
14.
PLoS One ; 15(6): e0234076, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520965

RESUMO

This study investigated the effects of oral administration of ß-glucan 1,3 (pharmaceutical grade 10%) on growth performance and carcass traits in two breeds of weanling rabbits adapted to survive in Egypt, New Zealand White (NZW) and Animal Production Research Institute (APRI) rabbits, with special attention to relative mRNA expression of interleukins and antioxidant enzyme genes, biochemical, and histological alterations. Oral administration of ß-glucan with doses 0.25 and 0.5 ml per one-liter of drinking water significantly accelerated body weight gain (BWG) in both rabbits' breeds, reduced total feed consumption (FC), and reduced feed conversion ratio (FCR), especially the 0.5 ml per one-liter dose in both rabbit breeds. There are remarkable differences in all the growth performance traits due to breed effect. The interaction effect between ß-glucan and breed significantly improved BWG, FC, and FCR. There were non-significant differences in all carcass traits studied due to oral administration of ß-glucan with both doses, except in dressing percentages. The highest of the dressing percentages were observed at doses 0.25 ml per one-liter (51%) and 0.5 ml per one-liter (52%) compared with control (50%). Our findings show significant variations in the final BW, total daily gain, feed consumption, and total feed conversion ratio between NZW and APRI rabbits. Absence of significant differences in the hot carcass weight and dressing percentage between the genetic groups had been reported in this study. Supplementing NZW and APRI rabbits with ß-glucan increased blood total protein and globulin. The duodenal villi dimensions, splenic lymphoid diameter, muscular fiber diameter, and muscular glycogen areas were significantly increased by ß-glucan administration. Expression of intestinal interleukin-18 (IL-18) in NZW rabbits treated with 0.25 and 0.5 doses of ß-glucan was significantly upregulated and enhanced the immune response. ß-glucan upregulated the expression of intestinal occludin mRNA particularly at dose 0.5 ß-glucan as well as upregulated intestinal superoxide dismutase 1 (SOD1) and glutathione peroxidase 1 (GPx1), which modulates anti-inflammatory and antioxidant properties. In conclusion, oral administration of ß-glucan at a dose of 0.25 or 0.5 ml per one-liter drinking water provided beneficial effects in the growth performance and health status of rabbits.


Assuntos
Mucosa Intestinal/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos , beta-Glucanas/farmacologia , Imunidade Adaptativa/efeitos dos fármacos , Administração Oral , Animais , Duodeno/metabolismo , Duodeno/patologia , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Interleucina-18/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Ocludina/genética , Ocludina/metabolismo , Coelhos , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Regulação para Cima/efeitos dos fármacos
16.
J Food Sci ; 85(6): 1752-1763, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32476138

RESUMO

Phenolics and carotenoids coexist in fruits and vegetables and could possess interaction effects after consumption. The present study aims to elucidate the possible mechanisms of the antioxidant interactions between anthocyanins and carotenoids using petunidin and lycopene as examples in hydrogen peroxide (H2 O2 )-induced heart myofibroblast cell (H9c2) line model. The results revealed that petunidin and lycopene showed antioxidant effects and petunidin in a larger proportion mixed with lycopene, for example, petunidin: lycopene = 9:1 significantly protected against the loss of the cell viability (8.98 ± 1.03%) and intracellular antioxidant enzyme activities of superoxide dismutase (SOD, 27.07 ± 3.51%), catalase (CAT, 29.51 ± 6.12%), and glutathione peroxidase (GSH-Px, 20.33 ± 2.65%). Moreover, the messenger RNA (mRNA) and protein expressions of NAD(P)H quinone reductase (NQO1) and heme oxygenase (HO-1) of the nuclear factor erythrocyte 2-related factor 2 (Nrf2) signaling pathway were significantly induced in petunidin, lycopene, and synergistic combinations, suggesting that the antioxidant action was through activating the Nrf2 antioxidant response pathway. This was further validated by Nrf2 siRNA, and the results that petunidin significantly induced more of NQO1 expression and lycopene more of HO-1 suggested that the synergism may be a result of concerted actions by the two compounds on these two different target genes of the Nrf2 pathway. The two compounds also significantly increased the phosphorylation of Akt in synergistic combinations. Findings of the present study demonstrated that petunidin and lycopene exerted synergistic antioxidant effects when petunidin in a larger proportion in the combinations and contribute to the prevention of cellular redox homeostasis, which might provide a theoretical basis for phenolics and carotenoids playing beneficial effects on the cardiovascular risk. PRACTICAL APPLICATION: In this study, we revealed that the combined treatments of petunidin and lycopen inhibited H2 O2 -induced oxidative damage in myocardial cells. Moreover, the treatments contributed to the Nrf2 pathway and the restoration of cellular redox homeostasis might provide a theoretical basis for phenolics and carotenoids playing beneficial effects on the cardiovascular risk.


Assuntos
Antocianinas/farmacologia , Antioxidantes/farmacologia , Peróxido de Hidrogênio/toxicidade , Licopeno/farmacologia , Miofibroblastos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Carotenoides/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Glutationa Peroxidase/metabolismo , Miofibroblastos/metabolismo , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo
17.
Medicine (Baltimore) ; 99(26): e20433, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590729

RESUMO

Bronchopulmonary dysplasia (BPD) is a chronic lung disease common in premature infants and is one of the leading causes of disability and death in newborns. The Keap-1/Nrf2 signaling pathway plays an important role in antioxidant and anti-inflammatory.Ten clean-grade, healthy pregnant Sprague-Dawley rats (purchased from Experimental Animal Center of Peking university, China) naturally gave birth to 55 neonatal rats from which 40 were selected and randomly divided into a hyperoxia group and a control group (N = 20, each). Thirty-two BPD patient samples are from Neonatal Department of the second Hospital of Jilin University from November 30, 2016 to May 1 2019.In present study, we observed that lung tissues of the control group did not undergo obvious pathological changes, whereas in the hyperoxia group, lung tissues had disordered structures. With increased time of hyperoxia exposure, the alveolar wall became attenuated. Under hypoxia conditions, the activity of oxidative stress-related enzymes (CAT, GSH-Px, SOD) in lung samples was significantly lower than that before treatment. The expression level of Keap1 mRNA and protein in the hyperoxia group was slightly lower than that of control group. The expression of Nrf2 and HO-1 mRNA and protein in the hyperoxia group was significantly higher than that of control group. For the infants with BPD, we found that the activity of SOD, GSH-Px, and CAT was significantly different from those of control group.We constructed a premature BPD animal model and found the abnormal of oxidative stress in different groups and the expression levels of Keap1/Nrf2 signaling pathway-related molecules, and we validated the results in premature infants with BPD.


Assuntos
Displasia Broncopulmonar/genética , Displasia Broncopulmonar/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Pulmão/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Animais , Animais Recém-Nascidos , Estudos de Casos e Controles , Catalase/metabolismo , Modelos Animais de Doenças , Feminino , Glutationa Peroxidase/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Hiperóxia , Hipóxia , Recém-Nascido Prematuro , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Pulmão/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/genética , Gravidez , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Superóxido Dismutase/metabolismo
18.
Ecotoxicol Environ Saf ; 200: 110715, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32450432

RESUMO

Copper (Cu) is a necessary trace mineral due to its biological activity. Excessive Cu can induce inflammatory response in humans and animals, but the underlying mechanism is still unknown. Here, 240 broilers were used to study the effects of excessive Cu on oxidative stress and NF-κB-mediated inflammatory responses in immune organs. Chickens were fed with diet containing different concentrations of Cu (11, 110, 220, and 330 mg of Cu/kg dry matter). The experiment lasted for 49 days. Spleen, thymus, and bursa of Fabricius (BF) on day 49 were collected for histopathological observation and assessment of oxidative stress status. Additionally, the mRNA and protein levels of NF-κB and inflammatory cytokines were also analyzed. The results indicated that excess Cu could increase the number and area of splenic corpuscle as well as the ratio of cortex and medulla in thymus and BF. Furthermore, excessive Cu intake could decrease activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px); but increase contents of malondialdehyde (MDA), TNF-α, IL-1, IL-1ß; up-regulate mRNA levels of TNF-α, IFN-γ, IL-1, IL-1ß, IL-2, iNOS, COX-2, NF-κB and protein levels of TNF-α, IFN-γ, NF-κB, p-NF-κB in immune organs. In conclusion, excessive Cu could cause pathologic changes and induce oxidative stress with triggered NF-κB pathway, and might further regulate the inflammatory response in immune organs of chicken.


Assuntos
Galinhas/imunologia , Cobre/toxicidade , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Bolsa de Fabricius/enzimologia , Bolsa de Fabricius/imunologia , Bolsa de Fabricius/metabolismo , Bolsa de Fabricius/patologia , Catalase/metabolismo , Galinhas/genética , Galinhas/metabolismo , Citocinas/genética , Citocinas/metabolismo , Glutationa Peroxidase/metabolismo , Inflamação/genética , Inflamação/metabolismo , Malondialdeído/metabolismo , NF-kappa B/genética , Baço/enzimologia , Baço/imunologia , Baço/metabolismo , Baço/patologia , Superóxido Dismutase/metabolismo , Timo/enzimologia , Timo/imunologia , Timo/metabolismo , Timo/patologia
19.
Life Sci ; 254: 117770, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32407846

RESUMO

AIMS: Cadmium chloride has various industrial applications and considered an industrial and environmental pollutant. The aim of this study was to evaluate the effect of atorvastatin on Cadmium chloride-induced hepatotoxicity in male rats. MATERIALS AND METHODS: Fifty-six adult male rats, randomly were divided into 8 groups. Groups 1-3 were received atorvastatin (20 mg/kg) intragastrically for 15 days during which Cadmium chloride (1, 2, and 3 mg/kg) were given intraperitoneally from days 8 to 15. Groups 4-6 were as first three groups but animals were received vehicle of atorvastatin. Group 7 was received vehicle of atorvastatin and vehicle of Cadmium chloride and Group 8 was received atorvastatin and vehicle of Cadmium chloride according to timeline of other groups. On day 16, under full anesthesia, blood sampling was prepared from heart, and livers were dissected out to analyses the biochemical and histopathology studies. KEY FINDINGS: Cadmium chloride significantly increased aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) in the serum. Malondialdehyde (MDA) significantly increased and superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione (GSH) significantly decreased the in the liver following Cadmium chloride administration. Atorvastatin significantly improved the levels of MDA, SOD, GPx, GSH, but not ALT, AST, and ALP in Cadmium chloride-treated rats. In histopathological studies, atorvastatin could not improve injured liver tissues induced by Cadmium chloride. SIGNIFICANCE: Atorvastatin has beneficial effects in improving Cadmium chloride-induced antioxidative enzymes disturbance which may be contribute to improving liver function in male rats.


Assuntos
Atorvastatina/farmacologia , Alanina Transaminase/sangue , Fosfatase Alcalina/metabolismo , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/sangue , Atorvastatina/metabolismo , Cádmio/toxicidade , Cloreto de Cádmio/efeitos adversos , Cloreto de Cádmio/farmacologia , Cloreto de Cádmio/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
20.
PLoS One ; 15(5): e0232160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32379770

RESUMO

There is interest in supplementing animals and humans with selenium (Se) above Se-adequate levels, but the only good biomarker for toxicity is tissue Se. We targeted liver because turkeys fed 5 µg Se/g have hepatic Se concentrations 6-fold above Se-adequate (0.4 µg Se/g) levels without effects on growth or health. Our objectives were (i) to identify transcript biomarkers for high Se status, which in turn would (ii) suggest proteins and pathways used by animals to adapt to high Se. Turkey poults were fed 0, 0.025, 0.4, 0.75 and 1.0 µg Se/g diet in experiment 1, and fed 0.4, 2.0 and 5.0 µg Se/g in experiment 2, as selenite, and the full liver transcriptome determined by RNA-Seq. The major effect of Se-deficiency was to down-regulate expression of a subset of selenoprotein transcripts, with little significant effect on general transcript expression. In response to high Se intake (2 and 5 µg Se/g) relative to Se-adequate turkeys, there were only a limited number of significant differentially expressed transcripts, all with only relatively small fold-changes. No transcript showed a consistent pattern of altered expression in response to high Se intakes across the 1, 2 and 5 µg Se/g treatments, and there were no associated metabolic pathways and biological functions that were significant and consistently found with high Se supplementation. Gene set enrichment analysis also found no gene sets that were consistently altered by high-Se and supernutritional-Se. A comparison of differentially expressed transcript sets with high Se transcript sets identified in mice provided high Se (~3 µg Se/g) also failed to identify common differentially expressed transcript sets between these two species. Collectively, this study indicates that turkeys do not alter gene expression in the liver as a homeostatic mechanism to adapt to high Se.


Assuntos
Selênio/metabolismo , Transcriptoma/efeitos dos fármacos , Perus/metabolismo , Animais , Biomarcadores/metabolismo , Dieta , Suplementos Nutricionais/toxicidade , Glutationa Peroxidase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Estado Nutricional , RNA Mensageiro/genética , Selenocisteína/genética , Selenoproteínas/genética , Selenoproteínas/metabolismo , Transcriptoma/genética , Perus/genética
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