RESUMO
PURPOSE: To evaluate the effects of taurine supplementation associated or not with chronic exercise on body composition, mitochondrial function, and expression of genes related to mitochondrial activity and lipid oxidation in the subcutaneous white adipose tissue (scWAT) of obese women. METHODS: A randomized and double-blind trial was developed with 24 obese women (BMI 33.1 ± 2.9 kg/m2, 32.9 ± 6.3 y) randomized into three groups: Taurine supplementation group (Tau, n = 8); Exercise group (Ex, n = 8); Taurine supplementation + exercise group (TauEx, n = 8). The intervention was composed of 3 g of taurine or placebo supplementation and exercise training for eight weeks. Anthropometry, body fat composition, indirect calorimetry, scWAT biopsy for mitochondrial respiration, and gene expression related to mitochondrial activity and lipid oxidation were assessed before and after the intervention. RESULTS: No changes were observed for the anthropometric characteristics. The Ex group presented an increased resting energy expenditure rate, and the TauEx and Ex groups presented increased lipid oxidation and a decreased respiratory quotient. Both trained groups (TauEx and Ex) demonstrated improved scWAT mitochondrial respiratory capacity. Regarding mitochondrial markers, no changes were observed for the Tau group. The TauEx group had higher expression of CIDEA, PGC1a, PRDM16, UCP1, and UCP2. The genes related to fat oxidation (ACO2 and ACOX1) were increased in the Tau and Ex groups, while only the TauEx group presented increased expression of CPT1, PPARa, PPARγ, LPL, ACO1, ACO2, HSL, ACOX1, and CD36 genes. CONCLUSION: Taurine supplementation associated with exercise improved lipid metabolism through the modulation of genes related to mitochondrial activity and fatty acid oxidation, suggesting a browning effect in the scWAT of obese women.
Assuntos
Tecido Adiposo Branco/metabolismo , Exercício Físico , Ácidos Graxos/metabolismo , Mitocôndrias/metabolismo , Obesidade/metabolismo , Taurina/administração & dosagem , Adulto , Composição Corporal/efeitos dos fármacos , Suplementos Nutricionais , Método Duplo-Cego , Metabolismo Energético/efeitos dos fármacos , Feminino , Expressão Gênica , Humanos , Peroxidação de Lipídeos/genética , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Oxirredução/efeitos dos fármacos , Placebos , Gordura SubcutâneaRESUMO
Leptin levels and oxidative stress are implicated in obesity risk. Reports of association of leptin gene (LEP) and leptin receptor gene (LEPR) polymorphisms with leptin elevation are contradictory in a diverse population. Only a few studies report the linkage of obesity with biochemical markers and genetic factors. OBJECTIVE: The aim of this study was to examine whether plasma lipid peroxidation, antioxidant capability, leptin levels are associate selected LEP -2548 A/G and LEPR Q223R polymorphisms in mestizo and indigenous obesity Mexican population. METHODS: We identified and characterized 50 overweight or obese subjects and 50 healthy, normal- weight volunteers with indigenous Tepehuana or Mexican mestizo ethnicity from Durango, Mexico. LEP -2548 A/G and LEPR Q223R polymorphisms were determined by genotyping. Concentrations of leptin, antioxidant capacity (CA) and lipoperoxidation (LIPX) were determined in fast conditions on plasma with Enzyme-Linked ImmunoSorbent Assay (ELISA) in all participants. RESULTS: The highest genotype frequency was the heterozygous LEPR, which was associated with lipid peroxidation levels in normal-weight Tepehuan populations. A positive correlation was observed (r = 0.5; p <0.01) between LEP polymorphism and lipoperoxidation in normal weight Tepehuan subjects. On the other hand, the LEPR polymorphism was associated with the level of lipoperoxidation (r = 0.13; P <0.05) in mestizo populations of normal weight. CONCLUSION: It is probable that there is a synergistic effect for obesity, where the presence of oxidative stress and single nucleotide polymorphisms (SNP) of leptin and its receptor contributes to the generation of pathological subcutaneous fat of obesity, together with the environmental conditions of the populations.
Assuntos
Povos Indígenas/genética , Leptina/genética , Obesidade/genética , Estresse Oxidativo/genética , Receptores para Leptina/genética , Adolescente , Adulto , Substituição de Aminoácidos , Arginina/genética , Estudos de Casos e Controles , Estudos Transversais , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença/etnologia , Ácido Glutâmico/genética , Humanos , Povos Indígenas/estatística & dados numéricos , Leptina/sangue , Peroxidação de Lipídeos/genética , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Obesidade/etnologia , Sobrepeso/etnologia , Sobrepeso/genética , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
Psoriasis is a chronic, autoimmune skin disease. In psoriasis, PON1 activity is diminished and peroxidation biomarkers are elevated. The most studied PON1 polymorphisms are rs662 (A > G) and rs854560 (A > T), which have been associated with the antioxidant activity of PON1, risk of cardiovascular diseases and psoriasis development. The aim of this study, was to determine the association of rs662 (A > G) and rs854560 (A > T) PON1 polymorphisms with psoriasis susceptibility in Western Mexico population. In this case-control study, we included 104 psoriasis patients and 124 control subjects. The genotyping of polymorphisms rs662 (A > G) and rs854560 (A > T) of PON1 was carried out by PCR-RFLPs. The lipid profiles were quantified by enzymatic colorimetric method, and PON1 activity was determined by spectrophotometry. The lipid profile levels, except HDL-C and atherogenic index, were higher in patients vs. controls. Patients presented lower paraoxonase and arylesterase activity. The G allele of rs662 (A > G) is associated with risk for psoriasis, while the T allele of rs854560 (A > T) is associated with low susceptibility to psoriasis. The AG haplotype was more frequent within the patient group (p < 0.05). The AA and AG genotypes of rs662 (A > G) and TT and AA genotypes of rs854560 (A > T) are associated with lower PONase and ARE activity in patients vs. controls. Patients with the G allele of rs662 (G > A) and T alleles of rs854560 (A > T) show significant differences in the lipid levels in comparison to controls. These results suggest that carriers of G allele of rs662 (A > G) present a greater susceptibility to psoriasis.
Assuntos
Arildialquilfosfatase/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Psoríase/genética , Adulto , Idoso , Alelos , Biomarcadores , Feminino , Genótipo , Haplótipos/genética , Humanos , Peroxidação de Lipídeos/genética , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Psoríase/epidemiologia , Psoríase/patologiaRESUMO
Agricultural expansion and the consequent use of pesticides lead to the loss and fragmentation of natural habitats of several wild species. Then, many species are inevitably exposed to a wide amount of pesticide formulations. Glyphosate (GLY)-based formulations are the most used herbicide, whereas two of the most employed insecticides are chlorpyrifos (CPF) and cypermethrin (CYP). The aim of this study was to evaluate genotoxicity, oxidative damage, and the modulation of antioxidants defenses in peripheral blood of Caiman latirostris after embryonic exposure to pesticide formulations and their mixtures. Pesticides concentrations employed were equivalent to those recommended in agricultural practices for application in soybean crops and a half of them: GLY: 2% and 1%; CYP: 0.12% and 0.06%; CPF: 0.8% and 0.4%. Two similar experiments (E1 and E2) were carried out in consecutive years, where C. latirostris eggs were exposed to pesticide formulations separately and in different mixtures through application on the incubation material. After hatching, blood samples were taken and genotoxicity and oxidative stress was evaluated through the micronucleus (MN) test, the modified comet assay, the lipid peroxidation (LPO) levels and the activities of catalase (CAT) and superoxide dismutase (SOD) antioxidant enzymes. The results indicated the presence of DNA damage, oxidation of purines and pyrimidines, and increased frequency of micronucleus (FMN) in the case of GLY, CYP, and CPF formulations exposure, as well as in all the mixtures tested, with respect to the control groups. Specifically, the results observed for the mixtures would indicate independent action or antagonism of the components for DNA damage and base oxidation (purines and pyrimidines) and a possible potentiation interaction for the FMN in two binary mixtures. However, there were not differences regarding lipid peroxidation, the activity of antioxidant enzymes and growth parameters. This study proved that the use of pesticide formulations at concentrations used in the field generate deleterious genetic effects on this species, then, exposure to them could threaten its survival and health status.
Assuntos
Jacarés e Crocodilos/metabolismo , Dano ao DNA , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Óvulo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Praguicidas/toxicidade , Jacarés e Crocodilos/sangue , Jacarés e Crocodilos/genética , Animais , Antioxidantes/metabolismo , Argentina , Ensaio Cometa , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/genética , Testes para Micronúcleos , Óvulo/crescimento & desenvolvimento , Estresse Oxidativo/genéticaRESUMO
INTRODUCTION: The acute kidney injury (AKI) is characterized by a sudden glomerular filtration reduction. Renal or intrinsic causes of AKI include nephrotoxicity induced by exogenous agents like cisplatin, which causes oxidative stress altering the biochemical process and leading to apoptosis. Therefore, this research is aimed at analyzing the embryonic stem cells (ESC) nephroprotective effect in AKI induced by cisplatin, employing genetic, phenotypic, and microspectroscopic techniques. METHODS: Thirty mice were randomly divided into three groups (n = 10): the healthy, isotonic salt solution (ISS), and mouse embryonic stem cells (mESC) groups. The ISS and mESC groups were subjected to AKI using cisplatin; 24 h post-AKI received an intraperitoneal injection of ISS or 1 × 106 mESC, respectively. At days 4 and 8 post-AKI, five mice of each group were sacrificed to analyze the histopathological, genetic (PDK4 and HO-1), protein (p53), and vibrational microspectroscopic changes. RESULTS: Histopathologically, interstitial nephritis and acute tubular necrosis were observed; however, the mESC group showed a more preserved microarchitecture with high cellularity. Additionally, the PDK4 and HO-1 gene expression only increased in the ISS group on day 4 post-AKI. Likewise, p53 was more immunoexpressed at day 8 post-AKI in the ISS group. About biomolecular analysis by microspectroscopy, bands associated with lipids, proteins, and nucleic acids were evidenced. Besides, ratios related to membrane function (protein/lipid), unsaturated lipid content (olefinic/total lipid, olefinic/total CH2, and CH2/CH3), and lipid peroxidation demonstrated oxidative stress induction and lipid peroxidation increase mainly in the ISS group. Finally, the principal component analysis discriminated against each group; nonetheless, some data of the healthy and mESC groups at day 8 were correlated. CONCLUSIONS: The mESC implant diminishes cisplatin nephrotoxicity, once the protective effect in the reduction of lipid peroxidation was demonstrated, reflecting a functional and histological restoration.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Células-Tronco Embrionárias/metabolismo , Peroxidação de Lipídeos/genética , Injúria Renal Aguda/patologia , Animais , Humanos , CamundongosRESUMO
Rebaudioside A (Reb A) is a diterpenoid isolated from the leaves of Stevia rebaudiana (Bertoni) that has been shown to possess pharmacological activity, including anti-inflammatory and antioxidant properties. However, the ability of Reb A to prevent liver injury has not been evaluated. Therefore, we aimed to study the potential of Reb A (20 mg/kg; two times daily intraperitoneally) to prevent liver injury induced by thioacetamide (TAA) administration (200 mg/kg; three times per week intraperitoneally). In addition, cocultures were incubated with either lipopolysaccharide or ethanol. Antifibrotic, antioxidant and immunological responses were evaluated. Chronic TAA administration produced considerable liver damage and distorted the liver parenchyma with the presence of prominent thick bands of collagen. In addition, TAA upregulated the expression of α-smooth muscle actin, transforming growth factor-ß1, metalloproteinases 9, 2 and 13, and nuclear factor kappaB and downregulated nuclear erythroid factor 2. Reb A administration prevented all of these changes. In cocultured cells, Reb A prevented the upregulation of genes implicated in fibrotic and inflammatory processes when cells were exposed to ethanol and lipopolysaccharide. Altogether, our results suggest that Reb A prevents liver damage by blocking oxidative processes via upregulation of nuclear erythroid factor 2, exerts immunomodulatory effects by downregulating the nuclear factor-κB system and acts as an antifibrotic agent by maintaining collagen content.
Assuntos
Antioxidantes/uso terapêutico , Diterpenos do Tipo Caurano/uso terapêutico , Cirrose Hepática/prevenção & controle , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Células Cultivadas , Colágeno/metabolismo , Modelos Animais de Doenças , Diterpenos do Tipo Caurano/isolamento & purificação , Diterpenos do Tipo Caurano/farmacologia , Expressão Gênica/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/genética , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Estresse Oxidativo/genética , Ratos , Ratos Wistar , Stevia/química , Tioacetamida/toxicidadeRESUMO
BACKGROUND: Oxidative modifications have been observed in lipids and proteins in lipoproteins isolated from women with preeclampsia. Thus, newborns could also be susceptible to this damage directly through their mothers. In this study, we evaluated the oxidative profile of LDL-c and HDL-c lipoproteins isolated from the umbilical cord from newborns born to women with preeclampsia. METHODS: Thirty newborns born to women with preeclampsia and thirty newborns born to women with healthy pregnancies were included. Lipid-damage biomarkers, including conjugated dienes, lipohydroperoxides and malondialdehyde, were measured. The reduction of nitroblue tetrazolium, formation of dityrosines, and carbonylation of proteins were assessed as indicators of protein damage. The protective activity of paraoxonase-I on HDL-c particles was evaluated. The total antioxidant capacity and lipid profiles were quantified in plasma. Data were analysed using Student's t-tests and Pearson correlation coefficients. RESULTS: Compared with the control group, the preeclampsia group had an increase in the percentage of lipid damage in both lipoproteins. There was an increase of 23.3 and 19.9% for conjugated dienes, 82.4 and 21.1% for lipohydroperoxides, and 103.8 and 51.5% for malondialdehyde in LDL-c and HDL-c, respectively. However, these infants did not show evident damage in protein oxidation. The activity of the enzyme paraoxonase-I was decreased by 36.2%; by contrast, the total antioxidant capacity was increased by 40% (protein) and 28.8% (non-protein). CONCLUSIONS: The oxidative modifications that occur in HDL-c and LDL-c isolated from newborns from women with preeclampsia are mainly caused by lipoperoxidation processes related to evident paraoxonase-I inactivation. The absence of protein damage is likely linked to an increase in total antioxidant capacity. Therefore, antioxidant support could be helpful in reducing oxidative stress in mother/newborn dyads.
Assuntos
HDL-Colesterol/sangue , LDL-Colesterol/sangue , Lipoproteínas HDL/sangue , Pré-Eclâmpsia/sangue , Adulto , Antioxidantes/metabolismo , Biomarcadores/sangue , Feminino , Sangue Fetal , Feto/metabolismo , Humanos , Recém-Nascido , Peroxidação de Lipídeos/genética , Lipídeos/sangue , Malondialdeído/metabolismo , Oxirredução , Estresse Oxidativo/genética , Pré-Eclâmpsia/patologia , Gravidez , Triglicerídeos/sangueRESUMO
Epigallocatechin-3-gallate (EGCG) is a polyhydroxyphenol constituent of green tea (e.g., Camellia sinensis) with known antioxidant properties. Due to these properties, others have proposed it as a potential therapeutic agent for the treatment of Parkinson's disease (PD). Previously, we demonstrated that EGCG prolonged the lifespan and locomotor activity in wild-type Canton-S flies exposed to the neurotoxicant paraquat (PQ), suggesting neuroprotective properties. Both gene mutations and environmental neurotoxicants (e.g., PQ) are factors involved in the development of PD. Thus, the first aim of this study was to create a suitable animal model of PD, which encompasses both of these factors. To create the model, we knocked down dj-1-ß function specifically in the dopaminergic neurons to generate TH > dj-1-ß-RNAi/+ Drosophila melanogaster flies. Next, we induced neurotoxicity in the transgenic flies with PQ. The second aim of this study was to validate the model by comparing the effects of vehicle, EGCG, and chemicals with known antioxidant and neuroprotective properties in vivo (e.g., propyl gallate and minocycline) on life-span, locomotor activity, lipid peroxidation, and neurodegeneration. The EGCG treatment provided protection and prevention from the PQ-induced reduction in the life-span and locomotor activity and from the PQ-induced increase in lipid peroxidation and neurodegeneration. These effects were augmented in the EGCG-treated flies when compared to the flies treated with either PG or MC. Altogether, these results suggest that the transgenic TH > dj-1-ß-RNAi/+ flies treated with PQ serve as a suitable PD model for screening of potential therapeutic agents.
Assuntos
Catequina/análogos & derivados , Proteínas de Drosophila/deficiência , Proteínas do Tecido Nervoso/deficiência , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Paraquat/toxicidade , Animais , Animais Geneticamente Modificados , Antioxidantes/metabolismo , Catequina/farmacologia , Catequina/uso terapêutico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Proteínas de Drosophila/genética , Drosophila melanogaster , Feminino , Herbicidas/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/genética , Locomoção/efeitos dos fármacos , Locomoção/genética , Masculino , Minociclina/farmacologia , Minociclina/uso terapêutico , Proteínas do Tecido Nervoso/genética , Doenças Neurodegenerativas/genética , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/genética , Proteína Desglicase DJ-1 , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Prostaglandin reductase-1 (Ptgr1) is an alkenal/one oxidoreductase that is involved in the catabolism of eicosanoids and lipid peroxidation such as 4-hydroxynonenal (4-HNE). Recently, we reported that Ptgr1 is overexpressed in human clinical and experimentally induced samples of hepatocellular carcinoma (HCC). However, how the expression of this gene is regulated and its role in carcinogenesis are not yet known. Here, we studied parameters associated with antioxidant responses and the mechanisms underlying the induction of Ptgr1 expression by the activation of Nuclear Factor (erythroid-derived-2)-like-2 (NRF2). For these experiments, we used two protocols of induced hepatocarcinogenesis in rats. Furthermore, we determined the effect of PTGR1 on cell proliferation and resistance to oxidative stress in cell cultures of the epithelial liver cell line, C9. Ptgr1 was overexpressed during the early phase in altered hepatocyte foci, and this high level of expression was maintained in persistent nodules until tumors developed. Ptgr1 expression was regulated by NRF2, which bound to an antioxidant response element at -653bp in the rat Ptgr1 gene. The activation of NRF2 induced the activation of an antioxidant response that included effects on proteins such as glutamate-cysteine ligase, catalytic subunit, NAD(P)H dehydrogenase quinone-1 (NQO1) and glutathione-S-transferase-P (GSTP1). These effects may have produced a reduced status that was associated with a high proliferation rate in experimental tumors. Indeed, when Ptgr1 was stably expressed, we observed a reduction in the time required for proliferation and a protective effect against hydrogen peroxide- and 4-HNE-induced cell death. These data were consistent with data showing colocalization between PTGR1 and 4-HNE protein adducts in liver nodules. These findings suggest that Ptgr1 and antioxidant responses act as a metabolic adaptation and could contribute to proliferation and cell-death evasion in liver tumor cells. Furthermore, these data indicate that Ptgr1 could be used to design early diagnostic tools or targeted therapies for HCC.
Assuntos
Oxirredutases do Álcool/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Fator 2 Relacionado a NF-E2/genética , Animais , Antioxidantes/metabolismo , Carcinogênese/genética , Carcinoma Hepatocelular/metabolismo , Proliferação de Células/genética , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Peroxidação de Lipídeos/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Estresse Oxidativo/genética , Ratos , Transdução de Sinais/genéticaRESUMO
The present study evaluates the superoxide dismutase (SOD) and catalase (CAT) activities in a wild strain of Drosophila melanogaster and the genotoxic potential induced by Cas II-gly (a new antineoplastic drug) using the somatic mutation and recombination test. Larvae 48h old were treated with Cas II-gly in a range of 0-1.5mM and aliquot were taken every 24h to have individuals treated for 24, 48, 72h and adulthood as well. A dose-dependent toxicity and a significant increase in SOD and CAT activities were found after a 24 and 48h treatment with 0.5-1.5mM concentrations. The comparison of the effect in enzymes with mutation indicated a positive correlation with increased genetic damage, after 24 and 48h of exposure for all concentrations tested. The addition of the genetic damage induced in each exposure time showed a significant effect, but only the small single spots had a concentration-related increase.