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1.
Biotech Histochem ; 94(6): 420-428, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31017002

RESUMO

Despite their benefits, technological devices such as cell phones may also have deleterious effects on human health. Considerable debate continues concerning the effects of the electromagnetic field (EMF) emitted during cell phone use on human health. We investigated the effects of exposure to 900 megahertz (MHz) EMF during mid to late adolescence on the rat liver. Control (ContGr), sham (ShmGr) and EMF (EMFGr) groups of female rats were established. We exposed the EMFGr rats daily to 900 MHz EMF on postnatal days 35-59. ShmGr rats underwent sham procedures. No procedure was performed on ContGr rats. Rats were sacrificed on postnatal day 60 and the livers were extracted. One part of the liver was stained with Masson's trichrome or hematoxylin and eosin. The remaining tissue was used to measure oxidative stress markers including malondialdehyde, glutathione, catalase, superoxide dismutase, 8-hydroxydeoxyguanosine (8-OHdG) and nitrotyrosine. Total antioxidant status and total oxidant status were used to calculate the oxidative stress index. We found normal hepatic morphology in the ContGr and ShmGr groups. The EMFGr group exhibited occasional irregularities in the radial arrangement of hepatocytes, cytoplasmic vacuolization, hemorrhage, sinusoid expansion, hepatocyte morphology and edema. Biochemical analysis revealed that 8-OHdG and SOD levels in EMFGr decreased significantly compared to the ContGr and ShmGr groups. Exposure to a continuous 900 MHz EMF for 1 h daily during mid to late adolescence may cause histopathological and biochemical alterations in hepatic tissue.


Assuntos
Campos Eletromagnéticos , Fígado/metabolismo , Fígado/fisiologia , Superóxido Dismutase/efeitos dos fármacos , Envelhecimento , Animais , Antioxidantes/farmacologia , Biomarcadores/análise , Catalase/efeitos dos fármacos , Feminino , Glutationa/metabolismo , Glutationa/farmacologia , Fígado/efeitos dos fármacos , Fígado/patologia , Malondialdeído/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
2.
Chemosphere ; 222: 175-183, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30708151

RESUMO

Psychiatric pharmaceuticals are one of the most prescribed active substances globally. Bupropion (BPP) is an antidepressant that acts via inhibition of norepinephrine and dopamine reuptake. It has been found in various water matrices, and thus its effects on aquatic organisms must be studied. The present study aimed to evaluate the acute toxic effects of BPP on zebrafish (Danio rerio) early life stages. For developmental analysis, organisms were exposed for 168 h to concentrations ranging from 0 to 82000 µg/L. Two other experiments were performed by exposing embryos to a wide range of concentrations (from 0 to 50000 µg/L) in order to evaluate BPP effects on embryonic behavior, using the Zebrabox and testing at the biochemical level (acetylcholinesterase, glutathione-S-transferase, lactate dehydrogenase and catalase). Developmental analysis indicated that BPP had low acute toxicity with a calculated 168 h-LC50 of 50346 µg/L. Concentrations equal to or above 44800 µg/L elicited several effects such as hatching delay, edemas and tail deformities. However, concentrations from 7300 µg/L upwards elicited equilibrium alteration. Behavioral analysis showed that BPP affected zebrafish locomotor behavior by decreasing activity at 0.6 µg/L, increasing activity at 8.8 and 158 µg/L, and decreasing activity at 50000 µg/L. Biochemical analysis showed an increase of AChE activity at 158 and 2812 µg/L, an increase in GST at the highest concentrations, CAT alteration and increase of LDH at 0.6, 2812 and 50000 µg/L. We can conclude that BPP affects zebrafish early life stages at environmental concentrations.


Assuntos
Bupropiona/farmacologia , Embrião não Mamífero/efeitos dos fármacos , Peixe-Zebra/fisiologia , Acetilcolinesterase/efeitos dos fármacos , Animais , Organismos Aquáticos/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Bupropiona/toxicidade , Catalase/efeitos dos fármacos , Embrião não Mamífero/enzimologia , Glutationa Transferase/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade
3.
Med Sci Monit ; 25: 991-1000, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30718447

RESUMO

BACKGROUND Literature shows that serum selenium concentration is low in rheumatoid arthritis (RA) patients. Biochemical properties of nanoparticles (NPs) are depend in its medium dispersed. Biochemical properties could effectively alter the therapeutic potential of NPs. Phytochemicals could serve as suitable medium for dispersion of NPs. P-Coumaric acid (CA) known to have anti-inflammatory activity. MATERIAL AND METHODS In the present experiment, we investigated the anti-inflammatory effect of SeNPs dispersed in 1% CA against Complete Freund's adjuvant induced RA. Celecoxib was used as a reference drug. RESULTS Selenium NPs (SeNPs) size is maintained in 1% CA solution. We observed that supplementation with 500 µg/Kg body weight (b.w.) eNPs significantly restored the levels of thiobarbituric acid reactive substances, COX-2 activity, different antioxidant enzyme activities, and inflammatory cytokines (TNF-α, IL-1ß, IL-6, and MCP-1) in RA rats. The mRNA expression of antioxidant enzymes such as MnSOD, Cu/ZnSOD, ECSOD, CAT, and GPx1 was found to be downregulated, whereas COX-2 was upregulated in RA rats; however, the mRNA expression of CAT, GPx1, and COX-2 reverted back to near normal levels in SeNPs-treated animals. CONCLUSIONS The therapeutic potential of SeNPs was confirmed through histological observation of angle joints in different experimental animals. Our results collectively suggest that SeNPs dispersed in CA can be an effective therapeutic agent for inflammatory disorders like acute gouty arthritis.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Selênio/metabolismo , Selênio/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Artrite Experimental/tratamento farmacológico , Catalase/efeitos dos fármacos , Celecoxib/farmacologia , Ácidos Cumáricos/farmacologia , Ciclo-Oxigenase 2/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Glutationa Peroxidase/efeitos dos fármacos , Masculino , Nanopartículas Metálicas/uso terapêutico , Nanopartículas , Estresse Oxidativo/efeitos dos fármacos , Compostos Fitoquímicos/metabolismo , Compostos Fitoquímicos/uso terapêutico , Ratos , Ratos Wistar
4.
Mol Biol Rep ; 46(2): 2285-2292, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30756334

RESUMO

Oxidative stress occurs due to an imbalance between antioxidant defenses and pro-oxidant agents in brain. This condition has been associated to the pathogenesis of several brain diseases; therefore, increasing the use of compounds that exert antioxidant activity. Thus, the objective of this study was to evaluate, in vitro, the effect of isoflavones in: (1) lipid peroxidation, catalase activity and thiol groups in the presence of pro-oxidants: sodium nitroprusside or Fe2+/EDTA complex in rat brain homogenates; (2) the activity of the enzyme monoamine oxidase (MAO). As a result, the isoflavones reduced lipid peroxidation in a manner dependent on the concentration and protected against the reduction of catalase activity as well as the induced thiol oxidation in brain tissue. In addition, isoflavones inhibited MAO activity (MAO-A and MAO-B). Taken together, our results showed that isoflavones avoided oxidative stress and decreased the MAO activity, suggesting a promissory use in the treatment of neurodegenerative diseases.


Assuntos
Isoflavonas/metabolismo , Isoflavonas/uso terapêutico , Inibidores da Monoaminoxidase/metabolismo , Animais , Encéfalo/metabolismo , Catalase/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/farmacologia , Nitroprussiato/farmacologia , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/farmacologia
5.
Microb Pathog ; 128: 342-346, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30682524

RESUMO

2-(2-nitrovinyl) furan is a broad-spectrum antibacterial agent with activity against Gram-positive and Gram-negative bacteria. In this study, the contributions of reactive oxygen species, oxidative DNA damage and glutathione depletion to its activity against Acinetobacter baumannii was investigated. Inactivation of sodB, katG and recA lowered the minimum inhibitory concentration of 2-(2-nitrovinyl) furan. Furthermore, the inactivation increased the superoxide anion radical and hydrogen peroxide contents of 2-(2-nitrovinyl) furan-treated A. baumannii. Antioxidant (thiourea) reversed the elevated levels of superoxide anion radical and hydrogen peroxide. In addition, thiourea lowered the susceptibility of A. baumannii to 2-(2-nitrovinyl) furan. 2-(2-nitrovinyl) furan depleted reduced glutathione (GSH) contents of parental, sodB, katG and recA strains of A. baumannii. NAD+/NADH ratio parental, sodB, katG and recA strains of A. baumannii exposed to 2-(2-nitrovinyl) furan increased significantly. Inactivation of type-I NADH dehydrogenase lowered the reactive oxygen species generation in 2-(2-nitrovinyl) furan-treated A. baumannii. It is evident from this study that 2-(2-nitrovinyl) furan stimulates respiratory chain activity of A. baumannii leading to enhanced ROS generation, which depletes GSH and reacts with Fe2+ to produce hydroxyl radical that damage DNA.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/metabolismo , Antibacterianos/farmacologia , Dano ao DNA/efeitos dos fármacos , Furanos/farmacologia , Glutationa/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Compostos de Vinila/farmacologia , Antioxidantes/metabolismo , Proteínas de Bactérias/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Catalase/efeitos dos fármacos , Catalase/metabolismo , Peróxido de Hidrogênio/metabolismo , Radical Hidroxila/metabolismo , Radical Hidroxila/farmacologia , Testes de Sensibilidade Microbiana , NAD/metabolismo , NADH Desidrogenase/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Recombinases Rec A/efeitos dos fármacos , Recombinases Rec A/metabolismo , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Superóxidos/metabolismo , Tioureia/metabolismo
6.
Plant Biol (Stuttg) ; 21(4): 634-642, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30664832

RESUMO

Pogonatherum crinitum is a promising lead (Pb) hyperaccumulator due to its high Pb tolerance and accumulation ability. However, the mechanisms that support Pb accumulation and tolerance in P. crinitum are not yet clearly understood. An indoor hydroponic experiment was conducted by cultivating P. crinitum seedlings exposed to intermittent Pb stress for 60 days, divided into four stages (T1, T2, T3 and T4), with a 15-day duration per stage. The following concentrations of Pb were used: 0, 500, 0, 500 mg·l-1 and 0, 1000, 0, 1000 mg·l-1 ). Antioxidant enzyme activity, Pb concentration and subcellular distribution of Pb were measured at each of the above stages. The results showed that superoxide dismutase (SOD) activity in shoots, and SOD, peroxidase (POD) and malondialdehyde (MDA) activity in shoots and roots significantly increased from T1 (no Pb stress) to T2 (Pb stress) in both 500 mg·l-1 and 1000 mg·l-1 treatments; however, no significant difference was noted between stages T3 (no Pb stress) and T4 (Pb stress). There was no obvious effect of Pb stress on catalase (CAT) activity in shoots and roots among different stages. The Pb concentration in shoots was up to 5090.90 mg·kg-1 and 7573.57 mg·kg-1 , and the bioconcentration factor (BFC) was 10.18 and 7.57 for the 500 mg·l-1 and 1000 mg·l-1 treatments, respectively, which confirmed the Pb hyperaccumulator characteristics of P. crinitum. For plants under Pb stress, most of the Pb was fixed in the cell walls, with a smaller amount in leaves and root vacuoles. Both SOD and POD scavenging of reactive oxygen radicals and fixing and compartmentalisation of Pb in the cell wall might play important roles in detoxification of P. crinitum seedlings in response to Pb stress. There was no phased response of P. crinitum to intermittent Pb stress and the physiological response to Pb stress may be contiguous.


Assuntos
Catalase/efeitos dos fármacos , Chumbo/metabolismo , Peroxidase/efeitos dos fármacos , Proteínas de Plantas/efeitos dos fármacos , Poaceae/efeitos dos fármacos , Plântula/efeitos dos fármacos , Superóxido Dismutase/efeitos dos fármacos , Catalase/metabolismo , Relação Dose-Resposta a Droga , Chumbo/toxicidade , Malondialdeído/metabolismo , Peroxidase/metabolismo , Proteínas de Plantas/metabolismo , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/metabolismo , Poaceae/enzimologia , Poaceae/crescimento & desenvolvimento , Poaceae/metabolismo , Plântula/enzimologia , Plântula/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Frações Subcelulares/metabolismo , Superóxido Dismutase/metabolismo
7.
Int J Neurosci ; 129(4): 363-368, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30334640

RESUMO

AIM OF THE STUDY: Rotenone is a commonly used pesticide that inhibits complex I of the mitochondrial electron transport system. Rotenone exposed rats demonstrate many characteristics of Parkinson Disease (PD). Oxidative stress is one of the hallmarks of PD, being the major sources of ROS in the DA neurons. In recent years the strong connection between the intestinal environment and the function of the central nervous system (CNS) has gained widespread popularity. In order to explain the mechanism underlying the GI dysfunction in PD, we aimed to investigate oxidant-antioxidant status in the brain and intestine, as well as locomotor activity, in rotenone exposed zebrafish. MATERIALS AND METHODS: Adult zebrafish were exposed to 2 mg/L rotenone for 30 days. At the end of the experiment, locomotor activity was determined by simple observation. Lipid peroxidation (LPO), nitric oxide (NO) levels, superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) activities were determined in the homogenates. RESULTS: Locomotor activity decreased in the rotenone exposed zebrafish. LPO increased in both brain and intestines whereas NO increased only in the brain. Decreased GST and CAT activities were found in both tissues whereas SOD activity decreased only in the intestines. CONCLUSION: As a conclusion, the results of our study support the connection between gut and brain axis in rotenone exposed zebrafish by means of oxidative stress and NO for the first time in literature.


Assuntos
Encéfalo/efeitos dos fármacos , Catalase/efeitos dos fármacos , Glutationa Transferase/efeitos dos fármacos , Inseticidas/efeitos adversos , Intestinos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Óxido Nítrico/metabolismo , Rotenona/efeitos adversos , Superóxido Dismutase/efeitos dos fármacos , Proteínas de Peixe-Zebra/efeitos dos fármacos , Peixe-Zebra/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/enzimologia , Feminino , Inseticidas/administração & dosagem , Intestinos/enzimologia , Masculino , Rotenona/administração & dosagem
8.
Pathol Res Pract ; 215(1): 21-28, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30501931

RESUMO

Melanoma is the most aggressive skin tumour, which incidence is rising fast over the year. The metastatic stage of disease is extremely difficult to treat and the mortality rate is still high. Emerging evidence suggested that oxidative stress (OS) is involved in the pathophysiological pathways of several chronic diseases and in the transformation and progression of many common cancers, including melanoma. In particular, it has emerged that OS interacts with inflammatory and immune response, all taking part in the melanomagenic process. In light of the interest shown by the scientific community for this topic, it was analysed the association between melanoma and oxidative stress. A systematic review was performed according to PRISMA guideline employing PubMed database. It identified n = 29 articles which investigated this aspect. Melanoma cells resulted to have adaptive mechanisms to overcome effects of high reactive oxygen species (ROS) levels. Furthermore, OS influences the metastatic ability of melanoma cells and their resistance to therapy. Nonetheless, the included studies were conducted on heterogeneous patient population and with differences in the design of the studies and in the protocols. Therefore, it is mandatory performing further studies which analyze all the aspect of OS pathways: ROS imbalance, its effect to proliferation and metastasis, role of microenvironment, ROS effect to drug resistance. All this in order to understand the role of oxidative stress in the complex biology of melanoma and to provide possibilities of defining new strategy of therapy.


Assuntos
Antioxidantes/uso terapêutico , Melanoma/patologia , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Cutâneas/patologia , Antioxidantes/metabolismo , Catalase/efeitos dos fármacos , Catalase/metabolismo , Humanos , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/metabolismo
9.
Toxicol Ind Health ; 34(11): 787-797, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30269681

RESUMO

Exposure to bisphenol A (BPA), an endocrine disruptor and environmental toxicant, is associated with adverse estrogenic effects in both humans and wildlife species. Because the effects of BPA on the ovary at the cellular level are incompletely understood, the present study was designed to investigate the underlying mechanism of granulosa cell injury following BPA exposure. Eight-week-old female Wistar rats were treated with BPA (25 mg/kg BW/day for 9 days, intraperitonially) with or without pretreatment of the catalase-specific blocker 3-amino-1,2,4-triazole (ATZ; 1 g/kg BW/day for 5 days, intraperitonially). Different oxidative and antioxidant stress parameters, pro-inflammatory cytokines, and hormonal levels were measured. Catalase expression in isolated granulosa cells was analyzed by Western blot. There were noticeable increases in both nitric oxide and lipid peroxidation levels in the granulosa cells of the BPA-treated group with or without pretreatment with ATZ. Compared with the controls, BPA exposure resulted in a significant increase in pro-inflammatory cytokine levels that was further increased following pretreatment with ATZ. Results of the hormonal assays clearly showed a significant decrease in both estrogen and progesterone levels. In contrast, there was a significant increase in both serum follicle-stimulating hormone and luteinizing hormone levels following BPA exposure, with or without ATZ pretreatment. Results of Western blot analysis demonstrated decreased expression of catalase in the BPA-treated group and a further decrease in expression in the group treated with both BPA and ATZ. Our data suggest that catalase plays a role in mediating reproductive damage to granulosa cells exposed to BPA.


Assuntos
Amitrol (Herbicida)/farmacologia , Compostos Benzidrílicos/toxicidade , Catalase/antagonistas & inibidores , Células da Granulosa/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenóis/toxicidade , Animais , Catalase/efeitos dos fármacos , Citocinas/análise , Citocinas/metabolismo , Feminino , Ratos
10.
Mol Biol Rep ; 45(6): 2571-2584, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30315444

RESUMO

N-ethyl-N-nitrosourea (ENU) is highly used in rodent models of tumerogenesis/carcinogenesis. Xenografting human-cancer tissues/cells with estradiol (E2) treatment is also used to generate rodent-models of gynaecological cancers. The altered metabolic-redox environment leading to establishment of pre-tumorigenesis condition and their mechanism are less studied. Here, female Wister rats were treated with these drugs at their pre-tumerogenic dosage (one group ENU single intra-peritoneal dose of 90 mg/kg b.w. and another group were implanted with human breast tumor (stage-IIIB) and fed with 2.5 mg of 17ß-estradiol once in a week for 4 months). After 4 months, animals were sacrificed; their serum and liver tissues were tested. A brief comparison was made with a rat model (regarded as positive control) of toxicity induced by mutagenic environmental pollutant arsenic (0.6 ppm daily/4 weeks). The increase in serum alkaline phosphatase and glutamate-pyruvate transaminase suggests the possible organ toxicity is favoured by the increase in hepatic/systemic free radicals and oxidative stress in all drug application models. But the increase in the serum E2 level as noted in the ELISA data with impairment in the hepatic estrogen sulfotransferase (SULT1E1) protein expression (immuno-blot data) were noticed with interfered hepatic free-thiols only in ENU and xenograft-E2 group compared to arsenic group. It is also evident in the in vitro result from E2/GSH/NAC added hepatic slices with altered antioxidant regulations. Moreover, impairment in hepatic SOD1, catalase and glutathiole peroxidase activities (PAGEzymographic data), especially in the ENU-treated group makes them more vulnerable to the oxidative threat in creating pre-tumerogenic microenvironment. This is evident in the result of their higher DNA-damage and histological abnormalities. The Bioinformatics study revealed an important role of rSULT1E1 in the regulations of E2 metabolism. This study is important for the exploration of the pre-tumerogenic condition by ENU and E2 by impairing SULT1E1 expression and E2 regulations via oxidant-stress signalling. The finding may help to find new therapeutic-targets to treat gynaecological-cancers more effectively.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Estradiol/farmacologia , Etilnitrosoureia/farmacologia , Animais , Antioxidantes/metabolismo , Neoplasias da Mama/metabolismo , Catalase/efeitos dos fármacos , Catalase/metabolismo , Dano ao DNA/efeitos dos fármacos , Estradiol/sangue , Estradiol/metabolismo , Etilnitrosoureia/metabolismo , Feminino , Xenoenxertos , Humanos , Fígado/metabolismo , Oxidantes/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Sulfotransferases/efeitos dos fármacos , Sulfotransferases/genética , Superóxido Dismutase-1/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
11.
BMC Res Notes ; 11(1): 670, 2018 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-30223880

RESUMO

OBJECTIVE: Monosodium glutamate (MSG) has been marred by a lot of controversy on its safety. In a majority of experimental studies, administration of the compound has been parenteral, and yet little is known about MSG safety consumed as a food supplement. In this study, we assessed the effects of low concentrations of MSG on the activity of hydrogen scavenging, catalase activity and climbing as well as lifespan in male Drosophila melanogaster over a 30 days period since this has been sparsely studied. RESULTS: No significant differences were associated with MSG at 5%, 1%, 0.2%, 0.04% on hydrogen peroxide scavenging, negative geotaxis and lifespan in W1118 male D. melanogaster. Significant differences were found in 5% MSG on catalase activity, showing that high MSG concentrations would affect tissue health in male D. melanogaster. MSG consumed as a food supplement would be safe at concentrations below 5% MSG.


Assuntos
Drosophila melanogaster , Glutamato de Sódio/toxicidade , Animais , Catalase/efeitos dos fármacos , Catalase/metabolismo , Hidrogênio/metabolismo , Longevidade , Masculino
12.
Biol Res ; 51(1): 17, 2018 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-29891016

RESUMO

BACKGROUND: Improper control on reactive oxygen species (ROS) elimination process and formation of free radicals causes tissue dysfunction. Pineal hormone melatonin is considered a potent regulator of such oxidative damage in different vertebrates. Aim of the current communication is to evaluate the levels of oxidative stress and ROS induced damage, and amelioration of oxidative status through melatonin induced activation of signaling pathways. Hepatocytes were isolated from adult Labeo rohita and exposed to H2O2 at three different doses (12.5, 25 and 50 µM) to observe peroxide induced damage in fish hepatocytes. Melatonin (25, 50 and 100 µg/ml) was administered against the highest dose of H2O2. Enzymatic and non-enzymatic antioxidants such as malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) was measured spectrophotometrically. Expression level of heat shock proteins (HSP70 and HSP90), HSPs-associated signaling molecules (Akt, ERK, cytosolic and nuclear NFkB), and melatonin receptor was also measured by western blotting analysis. RESULTS: H2O2 induced oxidative stress significantly altered (P < 0.05) MDA and GSH level, SOD and CAT activity, and up regulated HSP70 and HSP90 expression in carp hepatocytes. Signaling proteins exhibited differential modulation as revealed from their expression patterns in H2O2-exposed fish hepatocytes, in comparison with control hepatocytes. Melatonin treatment of H2O2-stressed fish hepatocytes restored basal cellular oxidative status in a dose dependent manner. Melatonin was observed to be inducer of signaling process by modulation of signaling molecules and melatonin receptor. CONCLUSIONS: The results suggest that exogenous melatonin at the concentration of 100 µg/ml is required to improve oxidative status of the H2O2-stressed fish hepatocytes. In H2O2 exposed hepatocytes, melatonin modulates expression of HSP70 and HSP90 that enable the hepatocytes to become stress tolerant and survive by altering the actions of ERK, Akt, cytosolic and nuclear NFkB in the signal transduction pathways. Study also confirms that melatonin could act through melatonin receptor coupled to ERK/Akt signaling pathways. This understanding of the mechanism by which melatonin regulates oxidative status in the stressed hepatocytes may initiate the development of novel strategies for hepatic disease therapy in future.


Assuntos
Hepatócitos/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Melatonina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Western Blotting , Catalase/efeitos dos fármacos , Catalase/metabolismo , Peixes , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Hepatócitos/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Malondialdeído/metabolismo , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Espectrofotometria , Superóxido Dismutase/efeitos dos fármacos
13.
Malawi Med J ; 30(1): 1-5, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29868151

RESUMO

Background: The emergence and spread of drug-resistant Tuberculosis (TB) is a major public health threat. TB resistance originates in the course of treatment due to genomic mutations in Mycobacterium tuberculosis (MTB). An increase in new cases with drug-resistant TB could be an indicator of high levels of circulating resistant strains. This study was conducted to determine the occurrence and frequency of genomic mutations that mediate Isoniazid (INH) and Rifampicin (RIF) resistance among isolates from untreated TB cases in urban Blantyre, Malawi. Methods: A cross-sectional retrospective study was conducted on a panel of 141(n=141) MTB clinical isolates recovered between June 2010 and January 2012 from >2+ Ziehl-Neelsen smear positive new pulmonary-TB patients with no history of treatment. Frozen isolates were revived using the BACTEC MGIT detection system. DNA was extracted using GenoLyse DNA extraction kit and detection of genomic mutations was carried out using the GenoType MTBDRplus Ver 2.0 assay. Results: Out of the 141 isolates studied, 3 (2.1%) were found carrying mutations in the katG gene that confer resistance to Isoniazid (INH). No mutations were detected in the inhA promoter region gene that confer weak INH resistance or in the rpoB gene that confer Rifampicin resistance. All katG mutant genes had a S315T1 single point mutation, a genomic alteration that mediates high INH resistance. Conclusion: The katG mutant gene conferring resistance to INH was the only genomic mutation observed among the isolates studied and the frequency of occurrence was low. Our findings suggest low levels of circulating drug-resistant MTB strains in urban Blantyre, Malawi.


Assuntos
Antibióticos Antituberculose/farmacologia , Proteínas de Bactérias/genética , Isoniazida/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Rifampina/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/genética , Proteínas de Bactérias/efeitos dos fármacos , Catalase/efeitos dos fármacos , Estudos Transversais , RNA Polimerases Dirigidas por DNA/efeitos dos fármacos , Humanos , Malaui , Técnicas de Diagnóstico Molecular , Mutação , Mycobacterium tuberculosis/isolamento & purificação , Oxirredutases/efeitos dos fármacos , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas/genética , Estudos Retrospectivos
14.
Med Sci Monit ; 24: 3631-3636, 2018 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-29849019

RESUMO

BACKGROUND This study aimed to investigate the effect and underlying molecular mechanism of sinomenine (SIN) on ankylosing spondylitis (AS). MATERIAL AND METHODS To study the potential role of SIN in the pathogenesis of AS, an AS mouse model was established and mice were treated with different concentrations of SIN (10, 30, and 50 mg/kg, administered intraperitoneally). Markers of inflammation and oxidative stress were determined by ELISA assay. Western blot analysis and qRT-PCR were used to quantify the levels of related proteins and gene mRNA expression. RESULTS The results suggest that AS mice has higher levels of TNF-α, IL-1ß, and IL-6 (p<0.01 for all), and lower levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) (p<0.01 for all). SIN treatment reduced the level of TNF-α, IL-1ß, and IL-6 in a dose-dependent manner, and the levels of SOD, CAT, and GSH-PX were dose-dependently increased (p<0.05 for all). The results also revealed that NF-κBp65 expression decreased, while the level of IkB increased, in a dose-dependent manner, after SIN treatment in AS mice (p<0.05 for all). The level of p-p38 was dose-dependently reduced in AS mice by SIN treatment (p<0.05). Moreover, SIN inhibited Cox-2 expression in AS mice in a dose-dependent manner (p<0.05). CONCLUSIONS SIN has a beneficial role in AS through suppressing inflammatory mediators and by down-regulating oxidative stress via inhibiting the MAPKp38/NF-kB pathway and Cox-2 expression.


Assuntos
Morfinanos/farmacologia , Espondilite Anquilosante/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Catalase/efeitos dos fármacos , Modelos Animais de Doenças , Glutationa Peroxidase/efeitos dos fármacos , Inflamação/tratamento farmacológico , Interleucina-1beta/efeitos dos fármacos , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Morfinanos/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos
15.
Int J Med Mushrooms ; 20(5): 419-429, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29953357

RESUMO

Chronic kidney disease is a health burden worldwide but particularly in sub-Saharan Africa, with dwindling resources as a result of poor commodity export, devaluation of currencies, and corruption that had decreased the average family income and substantially increased the number of persons living on less than $1.90/day. Natural products are part of the healthcare delivery system in that part of the world. This study was conducted to evaluate the protective effects of Pleurotus tuber-regium on the kidneys of rats treated with carbon tetrachloride (CCl4) for 13 weeks. Sixty rats were divided into 6 groups, with 10 animals in each group. Group I (control) received olive oil (3 mL/kg) intraperitoneally twice weekly and were given feed and water ad libitum. Group II received CCl4 (3 mL/kg, 30% in olive oil) twice weekly. Groups III, IV, and V received 100, 200, and 500 mg/kg wild edible P. tuber-regium (33.3% in feed) daily, respectively, in addition to 3 mL/kg CCl4 twice weekly. Group VI received 500 mg/kg P. tuber-regium (33.3% in feed) daily. At the end of 13 weeks, the animals were sacrificed and kidney weights recorded. Serum concentrations of creatinine, urea, and fasting blood glucose were assayed. Malondialdehyde, ascorbic acid, α-tocopherol, superoxide dismutase, catalase, total glutathione, and peroxidase were measured in kidney homogenate. The kidneys were also histologically examined. Administration of CCl4 to rats significantly (P < 0.05) increased the absolute and relative kidney weights from 0.93 ± 0.04 and 0.38 ± 0.02 g in the control group to 1.30 ± 0.04 and 0.58 ± 0.02 g in the treated groups (Groups III, IV, and V), respectively. CCl4 administration increased the concentrations of creatinine, urea, fasting blood glucose, and malondialdehyde from 0.53 ± 0.05 mg/dL, 17.0 ± 1.10 mg/dL, 72 ± 2.80 mg/dL, and 1.40 ± 0.32 µmol/L in the control group to 0.84 ± 0.03 mg/dL, 43.0 ± 6.90 mg/dL, 77 ± 2.2 mg/dL, and 14.0 ± 3.5 µmol/L in the treated groups, respectively. The concentrations of ascorbic acid, α-tocopherol, superoxide dismutase, catalase, total glutathione, and peroxidase decreased significantly (P < 0.05) from 0.41 ± 0.02 mg/dL, 5.15 ± 0.21 µg/mL, 8.49 ± 0.38 units/mL, 75.20 ± 4.57 mU/mL, 1.62 ± 0.03 µg/mL, and 9.74 ± 0.40 mU/mL in the control group to 0.24 ± 0.03 mg/dL, 1.80 ± 0.11 µg/mL, 2.78 ± 0.30 units/mL, 31.9 ± 5.87 mU/mL, 0.36 ± 0.04 µg/mL, and 3.84 ± 0.22 mU/mL in the treated groups, respectively. Photomicrographs showed that P. tuber-regium prevented the fibrosis and tubular and Bowman capsule distortions observed in the CCl4-only group. P. tuber-regium is effective in protecting the kidneys against CCl4-induced damage.


Assuntos
Lesão Renal Aguda/prevenção & controle , Antioxidantes/administração & dosagem , Tetracloreto de Carbono/toxicidade , Rim/efeitos dos fármacos , Pleurotus/química , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/patologia , Animais , Antioxidantes/química , Tetracloreto de Carbono/administração & dosagem , Catalase/efeitos dos fármacos , Catalase/metabolismo , Carpóforos/química , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Rim/patologia , Testes de Função Renal , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo
16.
An Acad Bras Cienc ; 90(2): 1533-1542, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29898110

RESUMO

Most herbicides applied in crop field, stay in the soil for a period, affecting next crop or even the plants using as green manure. Nowadays, the use of herbicides grow to increase productivity, mainly in the grain producing region north of Rio Grande do Sul state. The objective of this study was to evaluate the effects of herbicides fomesafen and sulfentrazone on antioxidant system in Avena sativa1, Vicia sativa2, Raphanus sativus and Lupinus albus. The plants were exposed to varying concentrations of fomesafen3 (0, 0.125, 0.25 and 0.5 kg ha -1) and sulfentrazone (0, 0.3, 0.6 and 1.2 kg ha-1). For this, the activities of, ascorbat peroxidase, catalase and guaiacol enzymes were analyzed, and the levels of MDA were quantificated. Fomesafen and sulfentrazone promoted alterations in balance of plants generating oxidative stress and elicited the response of the antioxidant system of plants, mainly in the high doses of fomesafen, for the species V. sativa and R. sativus. At the same time, the 1,2 kg ha -1 dose of sulfentrazone generated lipid peroxidation for V. sativa, R. sativus and L. albus. Additionally, A. sativa was the species that demonstrated low alterations on antioxidant system with the exposure to herbicide fomesafen and sulfentrazone. Thus, we can we can suggest that the species present a better response in defense of the oxidative stress generated by the herbicides.


Assuntos
Benzamidas/farmacologia , Produtos Agrícolas/efeitos dos fármacos , Herbicidas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Sulfonamidas/farmacologia , Triazóis/farmacologia , Avena/efeitos dos fármacos , Catalase/efeitos dos fármacos , Lupinus/efeitos dos fármacos , Peroxidase/efeitos dos fármacos , Raphanus/efeitos dos fármacos , Especificidade da Espécie , Vicia sativa/efeitos dos fármacos
17.
Photodiagnosis Photodyn Ther ; 22: 233-240, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29709605

RESUMO

BACKGROUND: Pseudomonas aeruginosa is the etiological agent of systemic and skin infections that are often difficult to treat. Photodynamic therapy (PDT) and, more recently, phototherapy (PT), are emerging among antimicrobial treatments to be combined with antibiotics. Visible light, either alone or combined with a photosensitizer (PS), elicits photooxidative stress that induces microbial death. The response of bacteria to phototherapy seems to involve the antioxidant machinery. This study relies on the effects of detoxifying catalase A (KatA) in response to PDT and PT-induced photooxidative stress. METHODS: The photo- and photodynamic inactivation experiments have been targeted at P. aeruginosa PAO1 and its isogenic derivative katA- mutant. The microorganisms were irradiated by a wide-spectrum halogen-tungsten lamp or light-emitting diodes (LEDs). Two photosensitizers, Tetrakis-(1-methyl-4-pyridyl)-21H, 23porphine, tetra-p-tosylate (TMPyP) porphyrin and Toluidine Blue O (TBO), were applied as part of the photodynamic approach. RESULTS: P. aeruginosa katA- mutant was more sensitive than wild-type strain PAO1 to wide-spectrum light and blue LED (464 nm) treatments. The complementation of KatA, in katA- mutant, restored the light response of wild-type PAO1. Upon TBO treatment and irradiation by visible light (halogen lamp or LED), the sensitivity of katA- mutant was significant higher (p = 0.028 and p = 0.045, respectively) than that of the PAO1 strain. CONCLUSIONS: This study provides the first description of KatA in the response to photooxidative stress induced by photo- and photodynamic therapy.


Assuntos
Catalase/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Luz , Fotoquimioterapia/métodos , Porfirinas/farmacologia , Pseudomonas aeruginosa/enzimologia , Cloreto de Tolônio/farmacologia
18.
J Cell Physiol ; 233(11): 8731-8739, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29775204

RESUMO

Ochratoxin A (OTA), is a natural contaminant of the food chain worldwide involved in the development of different type of cancers in animals and humans. Several studies suggested that oxidative damage might contribute to increase the cytotoxicity and carcinogenicity capabilities of OTA. The aim of this study was to evaluate the possible protective effect of δ-tocotrienol (Delta), a natural form of vitamin E, against OTA-induced nephrotoxicity. Male Sprague-Dawley rats were treated with OTA and/or Delta by gavage for 14 days. Our results shown that OTA treatment induced the increase of reactive oxigen species production correlated to a strong reduction of Glomerular Filtration Rate (GFR) and absoluted fluid reabsorption (Jv) with conseguent significant increase in blood pressure. Consistent, we noted in the kidney of rats treated with OTA, an increase in malondialdheyde and dihydroethidium production and a reduction of the activity of the catalase, superoxide dismutase, and glutathione peroxidase. Conversly, in the rat group subjected to the concomitant treatment OTA plus Delta, we observed the restored effect, compared the OTA treatment group, on blood pressure, GFR, Jv, and all activities of renal antioxidant enzymes. Finally, as far as concern the tissue damage induced by OTA and measured evaluating fibronectin protein levels, we observed that in OTA plus Delta group this effect is not restored. Our findings releval that a mechanism underlying the renal toxicity induced by OTA is the oxidative stress and provide a new rationale to use a Delta in order to protect, at least in part, against OTA-induced nephrotoxicity.


Assuntos
Antioxidantes/administração & dosagem , Nefropatias/tratamento farmacológico , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Vitamina E/análogos & derivados , Animais , Catalase/efeitos dos fármacos , Taxa de Filtração Glomerular/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Peroxidase/genética , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Ocratoxinas/toxicidade , Oxirredução/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/genética , Vitamina E/administração & dosagem , Vitamina E/genética
19.
Bratisl Lek Listy ; 119(3): 167-174, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29536746

RESUMO

AIM: We investigated the effects of atorvastatin and N-acetyl cysteine in decreasing ischemia-reperfusion damage after detorsion of a volvulus of the cecum and ascending colon. METHODS: Wistar albino rats (250-300 g) were divided into four groups. A cecal-ascending colon volvulus was created by the intestinal clockwise 720° rotation. At the end of one hour, the bowel was detorsioned. Group I (n = 7) was the sham (laparotomy) group, Group II (n = 7) the control (no treatment, volvulus or detorsion), Group III (n = 7) (N-acetyl cysteine administered ) , and Group IV (n = 7) (atorvastatin administered ) group. Blood samples were collected from each group via peripheral veins and centrifuged one hour after detorsion. The parameters of ischemia including malondialdehyde, glutathione peroxidase, catalase, and superoxide dismutase were then observed in the serous fluid. RESULTS: Malondialdehyde and superoxide dismutase increased in the control group, whereas they were reduced in the Group III and Group IV (p = 0.005; p = 0.008, respectively). The glutathione peroxidase levels revealed no significant differences (p > 0.05), whereas the catalase levels of the group III was higher than in each of the other three groups (p < 0.001). Histopathological evaluation detected reduced lesioning of the organ in the groups which were given atorvastatin and N-acetyl cysteine. CONCLUSION: Atorvastatin and of N-acetyl cysteine have a similar preventive effect in experimental ischemia-reperfusion injury (Tab. 8, Fig. 6, Ref. 24).


Assuntos
Acetilcisteína/farmacologia , Atorvastatina/farmacologia , Doenças do Ceco/metabolismo , Ceco/efeitos dos fármacos , Depuradores de Radicais Livres/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Volvo Intestinal/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Catalase/efeitos dos fármacos , Catalase/metabolismo , Doenças do Ceco/patologia , Ceco/metabolismo , Ceco/patologia , Modelos Animais de Doenças , Feminino , Glutationa Peroxidase/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Volvo Intestinal/patologia , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologia , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo
20.
J Bacteriol ; 200(7)2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29358497

RESUMO

Reactive oxygen species such as peroxides play an important role in plant development, cell wall maturation, and defense responses. During nodulation with the host plant Medicago sativa, Sinorhizobium meliloti cells are exposed to H2O2 in infection threads and developing nodules (R. Santos, D. Hérouart, S. Sigaud, D. Touati, and A. Puppo, Mol Plant Microbe Interact 14:86-89, 2001, https://doi.org/10.1094/MPMI.2001.14.1.86). S. meliloti cells likely also experience oxidative stress, from both internal and external sources, during life in the soil. Here, we present microarray transcription data for S. meliloti wild-type cells compared to a mutant deficient in the key oxidative regulatory protein OxyR, each in response to H2O2 treatment. Several alternative sigma factor genes are upregulated in the response to H2O2; the stress sigma gene rpoE2 shows OxyR-dependent induction by H2O2, while rpoH1 expression is induced by H2O2 irrespective of the oxyR genotype. The activity of the RpoE2 sigma factor in turn causes increased expression of two more sigma factor genes, rpoE5 and rpoH2 Strains with deletions of rpoH1 showed improved survival in H2O2 as well as increased levels of oxyR and total catalase expression. These results imply that ΔrpoH1 strains are primed to deal with oxidative stress. This work presents a global view of S. meliloti gene expression changes, and of regulation of those changes, in response to H2O2IMPORTANCE Like all aerobic organisms, the symbiotic nitrogen-fixing bacterium Sinorhizobium meliloti experiences oxidative stress throughout its complex life cycle. This report describes the global transcriptional changes that S. meliloti makes in response to H2O2 and the roles of the OxyR transcriptional regulator and the RpoH1 sigma factor in regulating those changes. By understanding the complex regulatory response of S. meliloti to oxidative stress, we may further understand the role that reactive oxygen species play as both stressors and potential signals during symbiosis.


Assuntos
Regulação Bacteriana da Expressão Gênica , Estresse Oxidativo/genética , Proteínas Repressoras/genética , Sinorhizobium meliloti/genética , Transcrição Genética , Catalase/efeitos dos fármacos , Catalase/genética , Perfilação da Expressão Gênica , Proteínas de Choque Térmico/genética , Peróxido de Hidrogênio/farmacologia , Análise em Microsséries , Mutação , Estresse Oxidativo/efeitos dos fármacos , Proteínas Repressoras/deficiência , Proteínas Repressoras/efeitos dos fármacos , Fator sigma/genética , Sinorhizobium meliloti/efeitos dos fármacos , Sinorhizobium meliloti/enzimologia , Sinorhizobium meliloti/fisiologia , Fatores de Transcrição/genética
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