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OBJECTIVES: This study was to investigate the correlation between oxidative balance score (OBS) and the prevalence of kidney stones in the general adult population. MATERIALS AND METHODS: We conducted an analysis using data from the 2007-2018 National Health and Nutrition Examination Survey (NHANES) project, including 17,988 participants. The OBS was computed based on previous research, combining 16 dietary factors and 4 lifestyle factors. Multiple logistic regressions and restricted cubic spline (RCS) regressions were utilized to explore the associations between OBS and kidney stone prevalence. RESULTS: Our analysis included 1,622 adults with kidney stones and 16,366 adults without kidney stones. The average age of participants was 46.86 ± 0.27 years, with 50.72% being male. The median OBS was 22.00 (17.00, 27.00). After adjusting for all covariates, each one-unit increase in OBS was associated with a 3% decrease in kidney stone prevalence (odds ratio [OR] = 0.97 [0.96-0.98], P < 0.001). Moreover, compared to the first quartile, the fourth quartile of OBS (OR = 0.65 [0.50-0.84], P = 0.001) exhibited a negative association with kidney stone prevalence after adjusting for multiple variables. Furthermore, we observed a non-linear negative relationship between OBS and kidney stone prevalence, with inflection points at 18.2 (P for nonlinearity = 0.048). Stratified analysis did not identify any variables significantly affecting the results. CONCLUSION: Our findings indicate that a higher OBS is associated with a decreased prevalence of kidney stones in the general adult population.
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Cálculos Renais , Humanos , Cálculos Renais/epidemiologia , Cálculos Renais/metabolismo , Cálculos Renais/química , Masculino , Feminino , Pessoa de Meia-Idade , Prevalência , Adulto , Estresse Oxidativo , Inquéritos Nutricionais , Estudos TransversaisRESUMO
Neutrophils have recently gained recognition for their potential in the fight against cancer. Neutrophil plasticity between the N1 anti-tumor and N2 pro-tumor subtypes is now apparent, as is the ability to polarize these individual subtypes by interventions such as intratumoral injection of various agents including bacterial products or pro-oxidants. Metabolic responses and the production of reactive oxygen species (ROS) such as hydrogen peroxide act as potent chemoattractants and activators of N1 neutrophils that facilitates their recruitment and ensuing activation of a toxic respiratory burst in tumors. Greater understanding of the precise mechanism of N1 neutrophil activation, recruitment and regulation is now needed to fully exploit their anti-tumor potential against cancers both locally and at distant sites. This systematic review critically analyzes these new developments in cancer immunotherapy.
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Neoplasias , Neutrófilos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Neutrófilos/metabolismo , Explosão Respiratória , Imunoterapia , Neoplasias/metabolismoRESUMO
Fungi are considered among the most efficient microbial degraders of plastics, as they produce salient enzymes and can survive on recalcitrant compounds with limited nutrients. In recent years, studies have reported numerous species of fungi that can degrade different types of plastics, yet there remain many gaps in our understanding of the processes involved in biodegradation. In addition, many unknowns need to be resolved regarding the fungal enzymes responsible for plastic fragmentation and the regulatory mechanisms which fungi use to hydrolyse, assimilate and mineralize synthetic plastics. This review aims to detail the main methods used in plastic hydrolysis by fungi, key enzymatic and molecular mechanisms, chemical agents that enhance the enzymatic breakdown of plastics, and viable industrial applications. Considering that polymers such as lignin, bioplastics, phenolics, and other petroleum-based compounds exhibit closely related characteristics in terms of hydrophobicity and structure, and are degraded by similar fungal enzymes as plastics, we have reasoned that genes that have been reported to regulate the biodegradation of these compounds or their homologs could equally be involved in the regulation of plastic degrading enzymes in fungi. Thus, this review highlights and provides insight into some of the most likely regulatory mechanisms by which fungi degrade plastics, target enzymes, genes, and transcription factors involved in the process, as well as key limitations to industrial upscaling of plastic biodegradation and biological approaches that can be employed to overcome these challenges.
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In women, breast cancer is the most commonly diagnosed cancer (11.7% of total cases) and the leading cause of cancer death (6.9%) worldwide. Bioactive dietary components such as Sea buckthorn berries are known for their high carotenoid content, which has been shown to possess anti-cancer properties. Considering the limited number of studies investigating the bioactive properties of carotenoids in breast cancer, the aim of this study was to investigate the antiproliferative, antioxidant, and proapoptotic properties of saponified lipophilic Sea buckthorn berries extract (LSBE) in two breast cancer cell lines with different phenotypes: T47D (ER+, PR+, HER2-) and BT-549 (ER-, PR-, HER2-). The antiproliferative effects of LSBE were evaluated by an Alamar Blue assay, the extracellular antioxidant capacity was evaluated through DPPH, ABTS, and FRAP assays, the intracellular antioxidant capacity was evaluated through a DCFDA assay, and the apoptosis rate was assessed by flow cytometry. LSBE inhibited the proliferation of breast cancer cells in a concentration-dependent manner, with a mean IC50 of 16 µM. LSBE has proven to be a good antioxidant both at the intracellular level, due to its ability to significantly decrease the ROS levels in both cell lines (p = 0.0279 for T47D, and p = 0.0188 for BT-549), and at the extracellular level, where the ABTS and DPPH inhibition vried between 3.38-56.8%, respectively 5.68-68.65%, and 35.6 mg/L equivalent ascorbic acid/g LSBE were recorded. Based on the results from the antioxidant assays, LSBE was found to have good antioxidant activity due to its rich carotenoid content. The flow cytometry results revealed that LSBE treatment induced significant alterations in late-stage apoptotic cells represented by 80.29% of T47D cells (p = 0.0119), and 40.6% of BT-549 cells (p = 0.0137). Considering the antiproliferative, antioxidant, and proapoptotic properties of the carotenoids from LSBE on breast cancer cells, further studies should investigate whether these bioactive dietary compounds could be used as nutraceuticals in breast cancer therapy.
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Hippophae , Neoplasias , Humanos , Antioxidantes/química , Carotenoides/química , Hippophae/química , Células MCF-7 , Frutas/química , Extratos Vegetais/químicaRESUMO
Ascorbate (H2 A) is a well-known antioxidant to protect cellular components from free radical damage and has also emerged as a pro-oxidant in cancer therapies. However, such "contradictory" mechanisms underlying H2 A oxidation are not well understood. Herein, we report Fe leaching during catalytic H2 A oxidation using an Fe-N-C nanozyme as a ferritin mimic and its influence on the selectivity of the oxygen reduction reaction (ORR). Owing to the heterogeneity, the Fe-Nx sites in Fe-N-C primarily catalyzed H2 A oxidation and 4 e- ORR via an iron-oxo intermediate. Nonetheless, trace O2 â - produced by marginal N-C sites through 2 e- ORR accumulated and attacked Fe-Nx sites, leading to the linear leakage of unstable Fe ions up to 420â ppb when the H2 A concentration increased to 2â mM. As a result, a substantial fraction (ca. 40 %) of the N-C sites on Fe-N-C were activated, and a new 2+2 e- ORR path was finally enabled, along with Fenton-type H2 A oxidation. Consequently, after Fe ions diffused into the bulk solution, the ORR at the N-C sites stopped at H2 O2 production, which was the origin of the pro-oxidant effect of H2 A.
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Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by parenchymal scarring, leading progressively to alveolar architecture distortion, respiratory failure, and eventually death. Currently, there is no effective treatment for IPF. Previously, 3'5-dimaleamylbenzoic acid (3'5-DMBA), a maleimide, demonstrated pro-apoptotic, anti-inflammatory, and anti-cancer properties; however, its potential therapeutic effects on IPF have not been addressed. Bleomycin (BLM) 100 U/kg was administered to CD1 mice through an osmotic minipump. After fourteen days of BLM administration, 3'5-DMBA (6 mg/kg or 10 mg/kg) and its vehicle carboxymethylcellulose (CMC) were administered intragastrically every two days until day 26. On day 28, all mice were euthanized. The 3'5-DMBA effect was assessed by histological and immunohistochemical staining, as well as by RT-qPCR. The redox status on lung tissue was evaluated by determining the glutathione content and the GSH/GSSG ratio. 3'5-DMBA treatment re-established typical lung histological features and decreased the expression of BLM-induced fibrotic markers: collagen, α-SMA, and TGF-ß1. Furthermore, 3'5-DMBA significantly reduced the expression of genes involved in fibrogenesis. In addition, it decreased reduced glutathione and increased oxidized glutathione content without promoting oxidative damage to lipids, as evidenced by the decrease in the lipid peroxidation marker 4-HNE. Therefore, 3'5-DMBA may be a promising candidate for IPF treatment.
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Bleomicina , Fibrose Pulmonar Idiopática , Animais , Anti-Inflamatórios/farmacologia , Bleomicina/efeitos adversos , Colágeno/metabolismo , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Fator de Crescimento Transformador beta1/metabolismoRESUMO
In this study, organo-inorganic nanohybrids LHGd-MTSPP with enzyme-like activity were prepared by in situ intercalation of anionic 5,10,15,20-tetrakis-(4-sulfonatophenyl)porphyrin and its complexes with Zn(II) and Pd(II) (MTSPP, M = 2H, Zn(II) and Pd(II)) into gadolinium layered hydroxide (LHGd). The combination of powder XRD, CHNS analysis, FT-IR, EDX, and TG confirmed the layered structure of the reaction products. The basal interplanar distances in LHGd-MTSPP samples were 22.3-22.6 Å, corresponding to the size of an intercalated tetrapyrrole molecule. According to SEM data, LHGd-MTSPP hybrids consisted of individual lamellar nanoparticles 20-50 nm in thickness. The enzyme-like activity of individual constituents, LHGd-Cl and sulfoporphyrins TSPP, ZnTSPP and PdTSPP, and hybrid LHGd-MTSPP materials, was studied by chemiluminescence analysis using the ABAP/luminol system in phosphate buffer solution. All the individual porphyrins exhibited dose-dependent antioxidant properties with respect to alkylperoxyl radicals at pH 7.4. The intercalation of free base TSPP porphyrin into the LHGd preserved the radical scavenging properties of the product. Conversely, in LHGd-MTSPP samples containing Zn(II) and Pd(II) complexes, the antioxidant properties of the porphyrins changed to dose-dependent prooxidant activity. Thus, an efficient approach to the design and synthesis of advanced LHGd-MTSPP materials with switchable enzyme-like activity was developed.
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Porfirinas , Porfirinas/química , Gadolínio , Espectroscopia de Infravermelho com Transformada de Fourier , Hidróxidos/químicaRESUMO
OBJECTIVES: We investigated the influence of oral cannabidiol (CBD) on vacuous chewing movements (VCM) and oxidative stress parameters induced by short- and long-term administration of haloperidol in a rat model of tardive dyskinesia (TD). METHODS: Haloperidol was administered either sub-chronically via the intraperitoneal (IP) route or chronically via the intramuscular (IM) route to six experimental groups only or in combination with CBD. VCM and oxidative stress parameters were assessed at different time points after the last dose of medication. RESULTS: Oral CBD (5 mg/kg) attenuated the VCM produced by sub-chronic administration of haloperidol (5 mg/kg) but had minimal effects on the VCM produced by chronic administration of haloperidol (50 mg/kg). In both sub-chronic and chronic haloperidol groups, there were significant changes in brain antioxidant parameters compared with CBD only and the control groups. The sub-chronic haloperidol-only group had lower glutathione activity compared with sub-chronic haloperidol before CBD and the control groups; also, superoxide dismutase, catalase, and 2,2-diphenyl-1-picrylhydrazyl activities were increased in the sub-chronic (IP) haloperidol only group compared with the CBD only and control groups. Nitric oxide activity was increased in sub-chronic haloperidol-only group compared to the other groups; however, the chronic haloperidol group had increased malondialdehyde activity compared to the other groups. CONCLUSIONS: Our findings indicate that CBD ameliorated VCM in the sub-chronic haloperidol group before CBD, but marginally in the chronic haloperidol group before CBD. There was increased antioxidant activity in the sub-chronic group compared to the chronic group.
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My chemical training provided a somewhat different perspective of biolo-gical problems, in the problem itself and approaches to its solution. I was fortunate to have in my laboratory postdocs and students who shared this perspective and used appropriate tools to address problems in amphetamine pharmacology and air pollution toxicology. These apparently disparate areas of research shared two chemical reactions: prooxidant-based generation of reactive oxygen and formation of covalent bonds between electrophiles and biological nucleophiles. This article is an attempt to summarize that research and to identify those individuals who made the contributions.
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Preparações Farmacêuticas/química , Farmacologia/métodos , Toxicologia/métodos , Animais , HumanosRESUMO
BACKGROUND: Cardiac arrest (CA) results in loss of blood circulation to all tissues leading to oxygen and metabolite dysfunction. Return of blood flow and oxygen during resuscitative efforts is the beginning of reperfusion injury and is marked by the generation of reactive oxygen species (ROS) that can directly damage tissues. The plasma serves as a reservoir and transportation medium for oxygen and metabolites critical for survival as well as ROS that are generated. However, the complicated interplay among various ROS species and antioxidant counterparts, particularly after CA, in the plasma have not been evaluated. In this study, we assessed the equilibrium between pro- and anti-oxidants within the plasma to assess the oxidative status of plasma post-CA. METHODS: In male Sprague-Dawley rats, 10 min asphyxial-CA was induced followed by cardiopulmonary resuscitation (CPR). Plasma was drawn immediately after achieving return of spontaneous circulation (ROSC) and after 2 h post-ROSC. Plasma was isolated and analyzed for prooxidant capacity (Amplex Red and dihydroethidium oxidation, total nitrate and nitrite concentration, xanthine oxidase activity, and iron concentration) and antioxidant capacity (catalase and superoxide dismutase activities, Total Antioxidant Capacity, and Iron Reducing Antioxidant Power Assay). The consequent oxidative products, such as 4-Hydroxyl-2-noneal, malondialdehyde, protein carbonyl, and nitrotyrosine were evaluated to determine the degree of oxidative damage. RESULTS: After CA and resuscitation, two trends were observed: (1) plasma prooxidant capacity was lower during ischemia, but rapidly increased post-ROSC as compared to control, and (2) plasma antioxidant capacity was increased during ischemia, but either decreased or did not increase substantially post-ROSC as compared to control. Consequently, oxidation products were increased post-ROSC. CONCLUSION: Our study evaluated the disbalance of pro- and anti-oxidants after CA in the plasma during the early phase after resuscitation. This disequilibrium favors the prooxidants and is associated with increased levels of downstream oxidative stress-induced end-products, which the body's antioxidant capacity is unable to directly mitigate. Here, we suggest that circulating plasma is a major contributor to oxidative stress post-CA and its management requires substantial early intervention for favorable outcomes.
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Antioxidantes/análise , Reanimação Cardiopulmonar , Parada Cardíaca/terapia , Oxidantes/sangue , Animais , Masculino , Estresse Oxidativo , Ratos Sprague-DawleyRESUMO
To understand foraging strategies and behavioral flexibility in wild animals, it is important to evaluate the physiological costs imposed by foraging efforts and how these costs affect foraging and provisioning behavior. Oxidative stress is a possible physiological indicator associated with foraging behavior in wild seabirds, and may also affect their reproductive performance. However, no previous study has simultaneously recorded foraging behavior and the associated oxidative stress in wild seabirds. Using an integrative approach based on oxidative stress measurements and bio-logging techniques (i.e., the use of animal-borne sensors), we determined the relationships between foraging behavior and oxidative stress in chick-rearing streaked shearwaters Calonectris leucomelas in 2018 and 2019. To quantify their oxidative stress, we measured reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) in their plasma. We found that the d-ROMs levels were positively related to the maximum distance from the colony and the number of takeoffs, especially in 2019 when shearwaters flew further to forage. In 2018, when they flew relatively short distances, the BAP levels were positively related to the levels of their physical activity (overall dynamic body acceleration; ODBA). We conclude that longer and less successful foraging may lead to increase oxidative stress, while successful foraging may mitigate the oxidative stress of foraging by providing dietary antioxidants. Our results highlight that the combined data from bio-logging and oxidative stress measurements aid in evaluating the underlying physiological costs of foraging behavior in wild animals.
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Aves/fisiologia , Comportamento Alimentar/fisiologia , Estresse Oxidativo , Ração Animal , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Comportamento Animal , Feminino , Geografia , Masculino , Oxidantes/farmacologia , TemperaturaRESUMO
In cancer, mitochondrial functions are commonly altered. Directly involved in metabolic reprogramming, mitochondrial plasticity confers to cancer cells a high degree of adaptability to a wide range of stresses and to the harsh tumor microenvironment. Lack of nutrients or oxygen caused by altered perfusion, metabolic needs of proliferating cells, co-option of the microenvironment, control of the immune system, cell migration and metastasis, and evasion of exogenous stress (e.g., chemotherapy) are all, at least in part, influenced by mitochondria. Mitochondria are undoubtedly one of the key contributors to cancer development and progression. Understanding their protumoral (dys)functions may pave the way to therapeutic strategies capable of turning them into innocent entities. Here, we will focus on the production and detoxification of mitochondrial reactive oxygen species (mtROS), on their impact on tumorigenesis (genetic, prosurvival, and microenvironmental effects and their involvement in autophagy), and on tumor metastasis. We will also summarize the latest therapeutic approaches involving mtROS.
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Mitocôndrias/metabolismo , Neoplasias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Antioxidantes/metabolismo , Carcinogênese/metabolismo , Carcinogênese/patologia , Humanos , Mitocôndrias/patologia , Neoplasias/patologia , Fosforilação OxidativaRESUMO
INTRODUCTION: Unroasted green coffee bean is an increasingly popular beverage and weight loss supplement that contains higher levels of chlorogenic acid derivatives and lower alkaloid levels than roasted beans. Nonetheless, how the gut microbiome metabolizes green coffee constituents has not been studied. OBJECTIVES: To identify possible biotransformation products of green coffee extract by the human gut microbiome, and the potential implications of this process on its biological effects or fate inside the body. METHODS: Molecular networking via the GNPS platform was employed for the visualization of green coffee metabolite profiles acquired using LC-tandem mass spectrometry post-incubation with an ex vivo culture of the human gut microbiome. RESULTS: 36 Metabolites were annotated including four unreported alkyl cinnamate esters in green coffee along with six novel biotransformation products. CONCLUSION: Our finding reveals new biotransformation products of cinnamate esters by the gut microbiome mediated via oxidative reactions such as dehydrogenation and hydroxylation, along with methylation, decarboxylation, and deglycosylation. These findings reveal potential interactions between the gut microbiome and green coffee constituents, and paves the way towards studying the effects of these interactions on both microbiome and the human host.
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Café/metabolismo , Microbioma Gastrointestinal/fisiologia , Metaboloma/fisiologia , Biomarcadores/análise , Biotransformação , Cromatografia Líquida/métodos , Cinamatos/metabolismo , Café/química , Humanos , Espectrometria de Massas/métodos , Metaboloma/genética , Metabolômica/métodos , Microbiota/fisiologia , Fenóis/metabolismo , Folhas de Planta/metabolismoRESUMO
In this study, we have studied the cytotoxicity and genotoxic potency of 3 pro-oxidants; H2O2, menadione and KBrO3 in different dosing scenarios, namely acute (1-day dosing) and chronic (5-days). For this purpose, relative population doubling (RPD%) and mononucleated micronucleus (MN) test were used. TK6 cells and NH32 were employed in in vitro experiments. In the study, the total acute dose was divided into 5 days for each prooxidant chemicals by dose fractionation (1/5th per day) method. Acute dosing was compared to chronic dosing. The oxidative stress caused by the exposure of cells with pro-oxidant chemicals to the cells was determined by an optimized 2',7'-dichlorofluorescein diacetate (DCFHDA) test method. The antioxidant levels of the cell lines were altered with buthionine sulfoxide (BSO) and N-acetyl cysteine (NAC), and the effect of antioxidant capacity on the MN formation in the cells was observed with this method. In the case of H2O2 and menadione, fractional dosing has been observed to result in lower toxicity and lower genotoxicity. But in the case of KBrO3, unlike the other 2 pro-oxidants, higher MN induction was observed with fractionated doses. DCFHDA test clearly demonstrated ROS induction with H2O2 and menadione but not with KBrO3. Unexpectedly, DCFHDA test demonstrated that KBrO3 did not cause an increase ROS levels in both acute and chronic dosing, suggesting an alternative ROS induction mechanism. It was also observed that, treatment with BSO and NAC, caused increasing and decreasing of MN fold change respectively, allowing further ROS specific mechanisms to be explored. Hence, dose fractionation expectedly caused less MN, cytotoxicity and ROS formation with H2O2 and menadione exposure, but not with KBrO3. This implies a unique mechanism of action for KBrO3 induced genotoxicity. Chronic dosing in vitro may be a valuable approach allowing better understanding of how chemicals damage DNA and pose human hazards.
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Dano ao DNA/efeitos dos fármacos , Testes de Mutagenicidade/métodos , Mutagênicos/administração & dosagem , Oxidantes/administração & dosagem , Proteína Supressora de Tumor p53/genética , Linhagem Celular , Células Cultivadas , Resistência a Medicamentos/genética , Glutationa/metabolismo , Humanos , Peróxido de Hidrogênio/administração & dosagem , Peróxido de Hidrogênio/toxicidade , Testes para Micronúcleos/métodos , Mutagênicos/toxicidade , Oxidantes/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/deficiência , Vitamina K 3/metabolismoRESUMO
BACKGROUND: Fetal oxidative balance (achieved when protective prenatal factors counteract sources of oxidative stress) might be critical for preventing asthma and allergic disease. OBJECTIVE: We examined prenatal intakes of hypothesized protective nutrients (including antioxidants) in conjunction with potential sources of oxidative stress in models of adolescent asthma and allergic disease. METHODS: We used data from 996 mother-child pairs in Project Viva. Exposures of interest were maternal prepregnancy body mass index and prenatal nutrients (energy-adjusted intakes of vitamins D, C, and E; ß-carotene; folate; choline; and n-3 and n-6 polyunsaturated fatty acids [PUFAs]), air pollutant exposures (residence-specific third-trimester black carbon or particulate matter with a diameter of less than 2.5 µm [PM2.5]), acetaminophen, and smoking. Outcomes were offspring's current asthma, allergic rhinitis, and allergen sensitization at a median age of 12.9 years. We performed logistic regression. Continuous exposures were log-transformed and modeled as z scores. RESULTS: We observed protective associations for vitamin D (odds ratio [OR], 0.69 [95% CI, 0.53-0.89] for allergic rhinitis), the sum of the n-3 PUFAs eicosapentaenoic acid and docosahexaenoic acid (OR, 0.81 [95% CI, 0.66-0.99] for current asthma), and the n-3 PUFA α-linolenic acid (OR, 0.78 [95% CI, 0.64-0.95] for allergen sensitization and OR, 0.80 [95% CI 0.65-0.99] for current asthma). Black carbon and PM2.5 were associated with an approximately 30% increased risk for allergen sensitization. No multiplicative interactions were observed for protective nutrient intakes with sources of oxidative stress. CONCLUSIONS: We identified potential protective prenatal nutrients (vitamin D and n-3 PUFAs), as well as adverse prenatal pro-oxidant exposures that might alter the risk of asthma and allergic disease into adolescence.
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Asma/sangue , Ácidos Graxos Ômega-3/sangue , Estresse Oxidativo , Terceiro Trimestre da Gravidez/sangue , Efeitos Tardios da Exposição Pré-Natal/sangue , Rinite Alérgica/sangue , Vitamina D/sangue , Adolescente , Asma/etiologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Rinite Alérgica/etiologiaRESUMO
Cancer prevention can be probably obtained with easier, faster and less financial strains by pursuing educational programs aimed to induce changes in lifestyle, starting from dietary habits. In the past decades, observational and case-control studies tried to establish a functional relationship between cancer mortality and morbidity and diet. The field becomes even more intricate when scientists investigated which dietary components are responsible for the putative, protective effects of fruits and vegetables against cancer. A relevant part of the literature focused on the positive role of "antioxidant" compounds in foods, including polyphenols. The present review critically evaluate clinical and pre-clinical studies based on polyphenol administration, which contributed to support the concept, deeply rooted in the general population, that antioxidant polyphenols can fight cancer. The controversial and contradictory issues related to the pros and cons on the use of polyphenols against cancer reflect the confounding assumption that cancer treatment and cancer prevention may overlap. We conclude that a clear cut must be done between these two concepts and that the experimental approaches to investigate one or the other should be significantly different, starting from adequate and specifically selected cellular models.
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Antioxidantes/uso terapêutico , Neoplasias/dietoterapia , Polifenóis/uso terapêutico , Humanos , Neoplasias/epidemiologiaRESUMO
Beside the key inhibition of acetylcholinesterase (AChE), involvement of oxidative stress in organophosphate (OP)-induced toxicity has been supported by experimental and human studies. On the other hand, according to our best knowledge, possible antioxidant properties of oximes, the only causal antidotes to OP-inhibited AChE, have been examined only by a few studies. Thus, we have determined the effect of four conventional (obidoxime, trimedoxime, pralidoxime, asoxime) and two promising experimental oximes (K027, K203) on dichlorvos (DDVP)-induced oxidative changes in vivo. Wistar rats (5/group) were treated with oxime (5% LD50 i.m) immediately after DDVP challenge (75% LD50 s.c). Oxidative stress biomarkers were determined in plasma and brain 60 min after the treatment: prooxidative-superoxide anion (O2·-) and total oxidative status (TOS); antioxidative-superoxide dismutase (SOD), total thiol (SH) groups, total antioxidant status (TAS) and paraoxonase (PON1); tissue oxidative stress burden-prooxidative-antioxidative balance (PAB) and oxidative stress index (OSI); oxidative tissue damage-malondialdehyde (MDA) and advanced oxidation protein products (AOPP). All oximes were able to attenuate DDVP-induced oxidative stress in rat plasma and brain. Changes of determined parameters in brain were not as prominent as it was seen in plasma. Based on OSI, better abilities of oxime K027, K203 and obidoxime to maintain DDVP-induced oxidative stress in rat brain were shown as compared to trimedoxime, pralidoxime and asoxime. Oximes can influence the complex in vivo redox processes that might contribute to their overall therapeutic efficacy. Further research is needed to understand the underlying molecular mechanisms involved in this phenomenon.
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Encéfalo/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Diclorvós/toxicidade , Intoxicação por Organofosfatos/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Oximas/farmacologia , Animais , Arildialquilfosfatase/sangue , Biomarcadores/sangue , Masculino , Malondialdeído/sangue , Cloreto de Obidoxima/farmacologia , Compostos de Pralidoxima , Compostos de Piridínio/farmacologia , Ratos , Superóxido Dismutase/sangue , Trimedoxima/farmacologiaRESUMO
The maternal allocation of carotenoids to eggs has been widely documented and manipulated. However, it is often assumed that the sole adaptive value of this allocation is to increase offspring fitness. Because carotenoids can be pro-oxidants or antioxidants depending on their concentrations and their chemical environment (i.e. presence of other antioxidants), dams may need to dispose of excess carotenoids upon depletion of other antioxidants to prevent oxidative damage. Additionally, the amount of carotenoids deposited in eggs may be dependent on male traits such as quality and coloration. We evaluated these two non-mutually exclusive hypotheses for carotenoid allocation to eggs and assessed paternal effects by supplementing male and female brown anole lizards, Anolis sagrei, with dietary carotenoids or with a combination of carotenoids and vitamin C. We found significant differences in the antioxidant capacities of fertilized and unfertilized eggs produced by female lizards, but the treatment did not affect the antioxidant capacity or carotenoid content of eggs. However, the carotenoid concentration of unfertilized eggs from carotenoid-supplemented females was significantly higher than eggs from the control group. Male coloration and body size did not affect the antioxidant capacity or carotenoid content of the eggs. Carotenoids may be allocated to unfertilized eggs to offset oxidative damage to the dam, with a neutral effect on offspring, rather than to solely provide antioxidant benefits to offspring as has been widely assumed.
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Carotenoides/metabolismo , Lagartos/fisiologia , Comportamento Materno , Óvulo/metabolismo , Animais , Tamanho Corporal , Cor , Feminino , Masculino , Estresse Oxidativo , Zigoto/metabolismoRESUMO
AIM: The main goal of this work was to highlight the significance of redox imbalance in the pathophysiology of bacterial vaginosis (BV). We studied the pro-oxidant (malondialdehyde) and antioxidants (glutathione, total antioxidant capacity) in the vaginal fluids of women and compared them on the basis of their Nugent score (NS). METHODS: Women were clinically screened using Amsel criteria (≥2 were regarded as positive) and were further screened for NS on the basis of microscopic examination. Subjects were classified into one of three groups - healthy controls, intermediate, and BV - on the basis of NS (0-3, 4-6, and 7-10, respectively). High vaginal swabs were collected from the study participants in order to estimate the levels of pro and antioxidants in the vaginal fluids. RESULTS: Our results indicated that levels of both pro- and antioxidants were elevated in high vaginal swabs of women in the intermediate (NS: 4-6) and BV (NS: 7-10) groups as compared to those of healthy control women. The difference in mean values for total antioxidant capacity and glutathione was found to be statistically significant. Furthermore, in the BV group (NS: ≥7) both antioxidants (glutathione and total antioxidant capacity) and the pro-oxidant, malondialdehyde, were found to be negatively correlated to NS. Interestingly, the correlation between NS and malondialdehyde was statistically significant. CONCLUSION: Our results suggest a significant correlation between redox imbalance and NS, which signifies changes in vaginal ecology from normal flora (Lactobacillus spp.) towards a more mixed bacterial population representing BV.
Assuntos
Oxirredução , Vagina , Vaginose Bacteriana , Adulto , Feminino , Humanos , Vagina/diagnóstico por imagem , Vagina/metabolismo , Vagina/microbiologia , Vaginose Bacteriana/diagnóstico , Vaginose Bacteriana/metabolismo , Vaginose Bacteriana/microbiologiaRESUMO
The aim of this study was to assess the effects of neonatal bisphenol A (BPA) administration on neuroendocrine features (the thyroid-brain axis). BPA (20 or 40 µg/kg) was orally administered to juvenile male albino rats ( Rattus norvegicus) from postnatal days (PNDs) 15 to 30. Both doses resulted in lower serum thyroxine (T4), triiodothyronine (T3), and growth hormone levels and higher thyrotropin level than the control levels at PND 30. In the neonatal cerebellum and cerebrum, vacuolation, pyknosis, edema, degenerative changes, and reductions in the size and number of the cells were observed in both treated groups. Alternatively, elevations in oxidative markers (lipid peroxidation, nitric oxide, and hydrogen peroxide [H2O2]) at both dose levels were recorded at PND 30, along with decreased activities of antioxidant markers (ascorbic acid, total thiol [t-SH], glutathione, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and catalase) with respect to control levels. Thus, the BPA-induced hypothyroid state may disturb the neonatal thyroid-brain axis via production of free radicals, and this could damage the plasma membrane and cellular components, delaying cerebrum and cerebellum development.