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The aim of this work was to evaluate possible mechanisms involved in the protective effect of N-acetyl-L-cysteine (NAC) on hepatic endocrine-metabolic, oxidative stress, and inflammatory changes in prediabetic rats. For that, normal male Wistar rats (60 days old) were fed for 21 days with 10% sucrose in their drinking water and 5 days of NAC administration (50 mg/kg, i.p.) and thereafter, we determined: serum glucose, insulin, transaminases, uric acid, and triglyceride levels; hepatic fructokinase and glucokinase activities, glycogen content, lipogenic gene expression; enzymatic and non-enzymatic oxidative stress, insulin signaling pathway, and inflammatory markers. Results showed that alterations evinced in sucrose-fed rats (hypertriglyceridemia, hyperinsulinemia, and high liver fructokinase activity together with increased liver lipogenic gene expression and oxidative stress and inflammatory markers) were prevented by NAC administration. P-endothelial nitric oxide synthase (P-eNOS)/eNOS and pAKT/AKT ratios, decreased by sucrose ingestion, were restored after NAC treatment. In conclusion, the results suggest that NAC administration improves glucose homeostasis, oxidative stress, and inflammation in prediabetic rats probably mediated by modulation of the AKT/NOS pathway. Administration of NAC may be an effective complementary strategy to alleviate or prevent oxidative stress and inflammatory responses observed in type 2 diabetes at early stages of its development (prediabetes).
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Estado Pré-Diabético , Ratos , Masculino , Animais , Acetilcisteína/farmacologia , Acetilcisteína/metabolismo , Estado Pré-Diabético/tratamento farmacológico , Ratos Wistar , Diabetes Mellitus Tipo 2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sacarose/farmacologia , Estresse Oxidativo , Insulina/metabolismo , Transdução de Sinais , Glucose/farmacologia , Óxido Nítrico/metabolismoRESUMO
Enzymes of the sulfur assimilation pathway of plants have been identified as potential targets for herbicide development, given their crucial role in synthesizing amino acids, coenzymes, and various sulfated compounds. In this pathway, O-acetylserine (thiol) lyase (OAS-TL; EC 2.5.1.47) catalyzes the synthesis of L-cysteine through the incorporation of sulfate into O-acetylserine (OAS). This study used an in silico approach to select seven inhibitors for OAS-TL. The in silico experiments revealed that S-benzyl-L-cysteine (SBC) had a better docking score (-7.0 kcal mol-1) than the substrate OAS (-6.6 kcal mol-1), indicating its suitable interaction with the active site of the enzyme. In vitro experiments showed that SBC is a non-competitive inhibitor of OAS-TL from Arabidopsis thaliana expressed heterologously in Escherichia coli, with a Kic of 4.29 mM and a Kiu of 5.12 mM. When added to the nutrient solution, SBC inhibited the growth of maize and morning glory weed plants due to the reduction of L-cysteine synthesis. Remarkably, morning glory was more sensitive than maize. As proof of its mechanism of action, L-cysteine supplementation to the nutrient solution mitigated the inhibitory effect of SBC on the growth of morning glory. Taken together, our data suggest that reduced L-cysteine synthesis is the primary cause of growth inhibition in maize and morning glory plants exposed to SBC. Furthermore, our findings indicate that inhibiting OAS-TL could potentially be a novel approach for herbicidal action.
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Arabidopsis , Herbicidas , Liases , Arabidopsis/metabolismo , Cisteína , Cisteína Sintase/metabolismo , Herbicidas/farmacologia , Plantas/metabolismo , Compostos de Sulfidrila/metabolismoRESUMO
This investigation aimed to assess the effect of N-acetylcysteine (NAC) as an adjuvant treatment to alleviate visceral leishmaniasis (VL). The present work includes both blinded randomized clinical intervention and experimental in vitro studies. The clinical trial included 60 patients with VL randomly allocated into two groups: a test group (n = 30) treated with meglumine antimoniate plus NAC (SbV + NAC) and a control group (n = 30) treated with meglumine antimoniate only (SbV). The primary outcome was clinical cure (absence of fever, spleen and liver sizes reduction, and hematological improvement) in 180 days. The cure rate did not differ between the groups; both groups had similar results in all readout indices. The immunological parameters of the patients treated with SbV + NAC showed higher sCD40L in sera during treatment, and the levels of sCD40L were negatively correlated with Interleukin-10 (IL-10) serum levels. In addition, data estimation showed a negative correlation between the sCD40L levels and the spleen size in patients with VL. For the in vitro experiments, peripheral blood mononuclear cells (PBMCs) or PBMC-derived macrophages from healthy donors were exposed to soluble Leishmania antigen (SLA) or infected with stationary promastigotes of Leishmania infantum in the presence or absence of NAC. Results revealed that NAC treatment of SLA-stimulated PBMCs reduces the frequency of monocytes producing IL-10 and lowers the frequency of CD4+ and CD8+ T cells expressing (pro-)inflammatory cytokines. Together, these results suggest that NAC treatment may modulate the immune response in patients with VL, thus warranting additional investigations to support its case use as an adjuvant to antimony therapy for VL.
Assuntos
Leishmania infantum , Leishmaniose Visceral , Humanos , Acetilcisteína/farmacologia , Acetilcisteína/uso terapêutico , Adjuvantes Imunológicos/uso terapêutico , Imunidade , Interleucina-10 , Leishmaniose Visceral/tratamento farmacológico , Leucócitos MononuclearesRESUMO
The disruption of neurodevelopment is a hypothesis for the emergence of schizophrenia. Some evidence supports the hypothesis that a redox imbalance could account for the developmental impairments associated with schizophrenia. Additionally, there is a deficit in glutathione (GSH), a main antioxidant, in this disorder. The injection of metilazoximetanol acetate (MAM) on the 17th day of gestation in Wistar rats recapitulates the neurodevelopmental and oxidative stress hypothesis of schizophrenia. The offspring of rats exposed to MAM treatment present in early adulthood behavioral and neurochemical deficits consistent with those seen in schizophrenia. The present study investigated if the acute and chronic (250 mg/kg) treatment during adulthood with N-acetyl-L-cysteine (NAC), a GSH precursor, can revert the behavioral deficits [hyperlocomotion, prepulse inhibition (PPI), and social interaction (SI)] in MAM rats and if the NAC-chronic-effects could be canceled by L-arginine (250 mg/kg, i.p, for 5 days), nitric oxide precursor. Analyses of markers involved in the inflammatory response, such as astrocytes (glial fibrillary acid protein, GFAP) and microglia (binding adapter molecule 1, Iba1), and parvalbumin (PV) positive GABAergic, were conducted in the prefrontal cortex [PFC, medial orbital cortex (MO) and prelimbic cortex (PrL)] and dorsal and ventral hippocampus [CA1, CA2, CA3, and dentate gyrus (DG)] in rats under chronic treatment with NAC. MAM rats showed decreased time of SI and increased locomotion, and both acute and chronic NAC treatments were able to recover these behavioral deficits. L-arginine blocked NAC behavioral effects. MAM rats presented increases in GFAP density at PFC and Iba1 at PFC and CA1. NAC increased the density of Iba1 cells at PFC and of PV cells at MO and CA1 of the ventral hippocampus. The results indicate that NAC recovered the behavioral deficits observed in MAM rats through a mechanism involving nitric oxide. Our data suggest an ongoing inflammatory process in MAM rats and support a potential antipsychotic effect of NAC.
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Oral halitosis is characterized by a foul, unpleasant breath that emanates from the oral cavity due to local or systemic conditions. Approximately 90% of offensive odors are caused by volatile sulfur compounds (VSCs). L-cysteine, used as a test solution to control bad breath, induces the formation of VSCs and serves as a preliminary rinse. The study aim was to investigate the effectiveness of L-cysteine solution in differentiating the origin of oral halitosis using a gas chromatography apparatus. Methods: In total, 37 patients with an average age of 49.56 years were evaluated and divided into two groups: halimetry before the use of L-cysteine (n= 37) and halimetry after the use of L-cysteine (n= 37). Patients over 18 years of age, without severe systemic health impairment or infectious/contagious diseases, and who did not use medicines that influenced their breath were included. Halimetry was performed using the OralCroma™ device. In the halimetry before the use of L-cysteine group, 5.40%, 5.40%, and 64.86% of the patients had high levels of sulfide, methyl mercaptan, and dimethyl sulfide, respectively. After the use of L-cysteine, 48.64%, 8.10%, and 37.84% of the patients had high levels of sulfide, methyl mercaptan, and dimethyl sulfide. In this study, L-cysteine proved to be important for the assessment of oral halitosis and effective in differentiating the origin of oral halitosis; therefore, this compound could be used for the differential diagnosis of oral halitosis origin using the OralChroma™ device.
Assuntos
Cisteína , Halitose , Adolescente , Adulto , Testes Respiratórios , Estudos de Casos e Controles , Diagnóstico Diferencial , Halitose/diagnóstico , Halitose/etiologia , Humanos , Pessoa de Meia-Idade , Compostos de Enxofre/análiseRESUMO
Oral mucositis is an inflammation of the oral mucosa mainly resulting from the cytotoxic effect of 5-fluorouracil (5-FU). The literature shows anti-inflammatory action of L-cysteine (L-cys) involving hydrogen sulfide (H2S). In view of these properties, we investigate the effect of L-cys in oral mucositis induced by 5-FU in hamsters. The animals were divided into the following groups: saline 0.9%, mechanical trauma, 5-FU 60-40 mg/kg, L-cys 10/40 mg and NaHS 27 µg/kg. 5-FU was administered on days 1st to 2nd; 4th day excoriations were made on the mucosa; 5th-6th received L-cys and NaHS. For data analysis, histological analyses, mast cell count, inflammatory and antioxidants markers, and immunohistochemistry (cyclooxygenase-2(COX-2)/inducible nitric oxide synthase (iNOs)/H2S) were performed. Results showed that L-cys decreased levels of inflammatory markers, mast cells, levels of COX-2, iNOS and increased levels of antioxidants markers and H2S when compared to the group 5-FU (p < 0.005). It is suggested that L-cys increases the H2S production with anti-inflammatory action in the 5-FU lesion.
Assuntos
Anti-Inflamatórios/farmacologia , Cisteína/farmacologia , Fluoruracila/toxicidade , Sulfeto de Hidrogênio/metabolismo , Inflamação/prevenção & controle , Estomatite/tratamento farmacológico , Animais , Antimetabólitos Antineoplásicos/toxicidade , Antioxidantes/farmacologia , Cricetinae , Ciclo-Oxigenase 2/metabolismo , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Estomatite/induzido quimicamente , Estomatite/imunologia , Estomatite/patologiaRESUMO
One of the main challenges facing materials science today is the synthesis of new biodegradable and biocompatible materials capable of improving existing ones. This work focused on the synthesis of new biomaterials from the bioconjugation of oleic acid with L-cysteine using carbodiimide. The resulting reaction leads to amide bonds between the carboxylic acid of oleic acid and the primary amine of L-cysteine. The formation of the bioconjugate was corroborated by Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, and nuclear magnetic resonance (NMR). In these techniques, the development of new materials with marked differences with the precursors was confirmed. Furthermore, NMR has elucidated a surfactant structure, with a hydrophilic part and a hydrophobic section. Ultraviolet-visible spectroscopy (UV-Vis) was used to determine the critical micellar concentration (CMC) of the bioconjugate. Subsequently, light diffraction (DLS) was used to analyze the size of the resulting self-assembled structures. Finally, transmission electron microscopy (TEM) was obtained, where the shape and size of the self-assembled structures were appreciated.
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OBJECTIVE: Reproductive toxicity is an important health challenge, mostly associated with exposure to several environmental toxicants. Arsenic is a ubiquitous toxic compound naturally present in the environment. This study was carried out to evaluate the dietary supplements of D-Ribose-L-Cysteine against sodium arsenate-induced testicular toxicity in adult male Wistar rats. METHODS: A total of 32 male rats (150-250g) were randomly divided into four (4) groups (n=8). Group A received normal saline as placebo; Group B received 8mg/kg BW of Sodium arsenate only; Group C received 8mg/kg BW of Sodium arsenate and 10 mg/kg BW of D-Ribose- L-cysteine; Group D received 8mg/kg BW of Sodium arsenate and 30 mg/kg BW of D-Ribose- L-cysteine. All administration was done via oral gavage for 28 days, thereafter the animals were sedated with pentobarbital sodium (intraperitoneally); we obtained testes and blood serum for analysis. RESULTS: The results showed abnormal testicular morphology with degeneration and decrease in spermatogonia, vacuolation and empty lumen, intense necrosis, spermatogenesis disruption (decrease sperm count, motility, viability) and degraded germinal epithelium of the seminiferous tubules, reduction in the hormone profile (FSH, LH, and TT) and oxidative stress parameters (CAT, GSH, and SOD) with a corresponding increase in MDA level in the arsenic-only treated rats (group B) compared to their control counterparts (group A), but it was ameliorated after DRLC administration, both in low and high doses, respectively. CONCLUSIONS: D-Ribose-L-Cysteine attenuated distorted testicular morphology, altered semen characteristics, hormone profile, and oxidative stress markers by preventing the deleterious toxicity of sodium arsenate.
Assuntos
Cisteína , Ribose , Animais , Arseniatos , Masculino , Ratos , Ratos Wistar , EspermatogêneseRESUMO
In this study, we examined the potential use of N-acetyl-L-cysteine (NAC) in association with a polyvalent antivenom and as stand-alone therapy to reduce the acute local and systemic effects induced by Lachesis muta muta venom in rats. Male Wistar rats (300-350 g) were exposed to L. m. muta venom (1.5 mg/kg - i.m.) and subsequently treated with anti-Bothrops/Lachesis serum (antivenom:venom ratio 1:3 'v/w' - i.p.) and NAC (150 mg/kg - i.p.) separately or in association; the animals were monitored for 120 min to assess changes in temperature, locomotor activity, local oedema formation and the prevalence of haemorrhaging. After this time, animals were anesthetized in order to collect blood samples through intracardiac puncture and then euthanized for collecting tissue samples; the hematological-biochemical and histopathological analyses were performed through conventional methods. L. m. muta venom produced pronounced local oedema, subcutaneous haemorrhage and myonecrosis, with both antivenom and NAC successfully reducing the extent of the myonecrotic lesion when individually administered; their association also prevented the occurrence of subcutaneous haemorrhage. Venom-induced creatine kinase (CK) release was significantly prevented by NAC alone or in combination with antivenom; NAC alone failed to reduce the release of hepatotoxic (alanine aminotransferase) and nephrotoxic (creatinine) serum biomarkers induced by L. m. muta venom. Venom induced significant increase of leucocytes which was also associated with an increase of neutrophils, eosinophils and monocytes; antivenom and NAC partially reduced these alterations, with NAC alone significantly preventing the increase of eosinophils whereas neither NAC or antivenom prevented the increase in monocytes. Venom did not induce changes in the erythrogram parameters. In the absence of a suitable antivenom, NAC has the potential to reduce a number of local and systemic effects caused by L. m. muta venom.
Assuntos
Venenos de Crotalídeos , Viperidae , Acetilcisteína/uso terapêutico , Animais , Antivenenos/uso terapêutico , Venenos de Crotalídeos/toxicidade , Masculino , Ratos , Ratos Wistar , Venenos de Víboras/toxicidadeRESUMO
Introduction: Several studies in the literature have evaluated the role of oxidative stress and adjuvant therapies for X-linked adrenoleukodystrophy (X-ALD). Here, we investigated whether n-acetyl-L-cysteine (NAC) and rosuvastatin (RSV) could influence the generation of reactive species, redox status and nitrative stress in fibroblasts from asymptomatic patients with X-ALD. Methods: Skin biopsy samples were cultured and treated for 2 hours (37 °C) with NAC and RSV. Results: X-ALD fibroblasts generated high levels of reactive oxygen species. These levels were significantly lower in fibroblasts treated with NAC and RSV relative to untreated samples. The X-ALD fibroblasts from asymptomatic patients also had higher catalase activity, and only NAC was able to increase enzyme activity in the samples. Conclusions: Our results indicated that NAC and RSV were able to improve oxidative stress parameters in fibroblasts from asymptomatic patients with X-ALD, showing that adjuvant antioxidant therapy may be a promising treatment strategy for asymptomatic patients with this disease. (AU)
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Humanos , Masculino , Feminino , Acetilcisteína , Estresse Oxidativo , Adrenoleucodistrofia/terapia , Rosuvastatina Cálcica , FibroblastosRESUMO
Generally, the selection of fructans prebiotics and probiotics for the formulation of a symbiotic has been based on arbitrary considerations and in vitro tests that fail to take into account competitiveness and other interactions with autochthonous members of the intestinal microbiota. However, such analyzes may be a valuable step in the development of the symbiotic. The present study, therefore, aims to investigate the effect of lactobacilli strains and fructans (prebiotic compounds) on the growth of the intestinal competitor Klebsiella oxytoca, and to assess the correlation with short-chain fatty acids production. The short-chain fatty acids formed in the fermentation of the probiotic/prebiotic combination were investigated using NMR spectroscopy, and the inhibitory activities were assessed by agar diffusion and co-culture methods. The results showed that Lactobacillus strains can inhibit K. oxytoca, and that this antagonism is influenced by the fructans source and probably associated with organic acid production.
Assuntos
Ácidos Graxos Voláteis/metabolismo , Frutanos/análise , Klebsiella oxytoca/fisiologia , Espectroscopia de Ressonância Magnética/métodos , Prebióticos/análise , Probióticos/análise , Fermentação/fisiologia , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Klebsiella oxytoca/ultraestrutura , Lactobacillus acidophilus/fisiologia , Lactobacillus acidophilus/ultraestrutura , Microscopia Eletrônica de VarreduraRESUMO
In the present work, we obtained polymeric diacetylene liposomes that can associate N-Acetyl-l-Cysteine (NAC), a broad spectrum mucolytic. The reason for studying these formulations is that they could be applied in the future as NAC delivery systems, with a possible dose reduction but maintaining its effect. Liposomes used herein are obtained by a photopolymerization reaction, thus gaining stability and rigidity. Lipids belonging to lung surfactant were added in different ratios to the formulations in order to maximize its possible interaction with the lung tissue. Because of lipopolymer stability, the oral or nasal route could be appropriated. This formulation could efficiently transport NAC to exert its mucolytic activity and help in diseases such as cystic fibrosis, which has abnormal mucus production. Also, this type of treatment could be useful in other types of diseases, interacting with the mucus layer and making the lung tissue more permeable to other therapies. Formulations so obtained presented high levels of polymerization. Also, they present small hollow fibers structures with a high number of polymeric units. These types of arrangements could present advantages in the field of drug delivery, giving the possibility of a controlled release. Lipopolymers with lipids from lung surfactant associated with NAC are promising complexes in order to treat not only respiratory illnesses. The stability of the formulation would allow its inoculation through other routes such as the oral one, helping the reposition of NAC as an antioxidant drug. Finally, these formulations are non-toxic and easy to produce.
Assuntos
Acetilcisteína/química , Fibrose Cística/tratamento farmacológico , Lipídeos/farmacologia , Polímeros/farmacologia , Surfactantes Pulmonares/química , Células A549 , Sobrevivência Celular/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Lipídeos/química , Tamanho da Partícula , Polímeros/química , Propriedades de SuperfícieRESUMO
AIMS: To investigate the effect of long-term N-acetyl-l-cysteine (NAC) treatment in Wistar rats subjected to renal ischemia and reperfusion (IR) and a chronic highsodium diet (HSD). MAIN METHODS: Adult male Wistar rats received an HSD (8.0% NaCl) or a normalsodium diet (NSD; 1.3% NaCl) and NAC (600â¯mg/L) or normal drinking water starting at 8â¯weeks of age. At 11â¯weeks of age, the rats from both diet and NAC or water treatment groups underwent renal IR or Sham surgery and were followed for 10â¯weeks. The study consisted of six animal groups: NSDâ¯+â¯Shamâ¯+â¯water; NSDâ¯+â¯IRâ¯+â¯water; NSDâ¯+â¯IRâ¯+â¯NAC; HSDâ¯+â¯Shamâ¯+â¯water; HSDâ¯+â¯IRâ¯+â¯water; and HSDâ¯+â¯IRâ¯+â¯NAC. KEY FINDINGS: Tail blood pressure (tBP) increased with IR and NAC treatment in the NSD group but not in the HSD group. The serum creatinine level was higher after NAC treatment in both diet groups, and creatinine clearance was decreased in only the HSDâ¯+â¯IRâ¯+â¯NAC group. Albuminuria increased in the HSDâ¯+â¯IRâ¯+â¯water group and decreased in the HSDâ¯+â¯IRâ¯+â¯NAC group. Kidney mass was increased in the HSDâ¯+â¯IR group and decreased with NAC treatment. Renal fibrosis was prevented with NAC treatment and cardiac fibrosis was decreased with NAC treatment in the HSDâ¯+â¯IR group. SIGNIFICANCE: NAC treatment promoted structural improvements, such as decreased albuminuria and fibrosis, in the kidney and heart. However, NAC could not recover kidney function or blood pressure from the effects of IR associated with an HSD. Therefore, in general, long-term NAC treatment is not effective and is deleterious to recovery of function after kidney injury.
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Acetilcisteína/farmacologia , Isquemia Encefálica/fisiopatologia , Rim/irrigação sanguínea , Traumatismo por Reperfusão/fisiopatologia , Cloreto de Sódio na Dieta/efeitos adversos , Injúria Renal Aguda/prevenção & controle , Animais , Pressão Sanguínea/efeitos dos fármacos , Isquemia Encefálica/metabolismo , Sequestradores de Radicais Livres/farmacologia , Isquemia/etiologia , Isquemia/metabolismo , Isquemia/patologia , Isquemia/fisiopatologia , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Ratos , Ratos Wistar , Reperfusão/métodos , Traumatismo por Reperfusão/metabolismo , Cloreto de Sódio na Dieta/administração & dosagemRESUMO
In the present paper, a new analytical preconcentration/speciation method for antimony species determination in bottled mineral water samples using the SiO2/Al2O3/SnO2 adsorbent was developed. The method is based on selective adsorption of Sb(III) ions by SiO2/Al2O3/SnO2 under a wide pH range (2.5-7.5). Total antimony was determined with previous sample treatment using 0.1% (w/v) l-cysteine and the concentration of Sb(V) species was determined by the difference between total and Sb(III). The proposed method provided an analytical curve ranging from 0.50 to 5.00⯵gâ¯L-1 (râ¯=â¯0.999), limit of detection (LD) of 0.17⯵gâ¯L-1 and preconcentration factor (PF) of 136-fold. The method exhibited tolerance to different metal ions and the accuracy was attested from addition and recovery tests (95.2-106.0%) in bottled mineral water samples using 2.0% (w/v) l-cysteine, as well as by analysis of certified material. Only Sb(III) species were determined in mineral water (0.54-1.04⯵gâ¯L-1).
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Antimônio/análise , Água Potável/análise , Águas Minerais/análise , Espectrofotometria Atômica/métodos , Óxido de Alumínio/química , Antimônio/química , Cisteína/química , Análise de Injeção de Fluxo , Limite de Detecção , Oxirredução , Dióxido de Silício/química , Compostos de Estanho/químicaRESUMO
X-linked adrenoleukodystrophy (X-ALD) is an inherited neurometabolic disorder caused by disfunction of the ABCD1 gene, which encodes a peroxisomal protein responsible for the transport of the very long-chain fatty acids from the cytosol into the peroxisome, to undergo ß-oxidation. The mainly accumulated saturated fatty acids are hexacosanoic acid (C26:0) and tetracosanoic acid (C24:0) in tissues and body fluids. This peroxisomal disorder occurs in at least 1 out of 20,000 births. Considering that pathophysiology of this disease is not well characterized yet, and glial cells are widely used in studies of protective mechanisms against neuronal oxidative stress, we investigated oxidative damages and inflammatory effects of vesicles containing lecithin and C26:0, as well as the protection conferred by N-acetyl-L-cysteine (NAC), trolox (TRO), and rosuvastatin (RSV) was assessed. It was verified that glial cells exposed to C26:0 presented oxidative DNA damage (measured by comet assay and endonuclease III repair enzyme), enzymatic oxidative imbalance (high catalase activity), nitrative stress [increased nitric oxide (NO) levels], inflammation [high Interleukin-1beta (IL-1ß) levels], and induced lipid peroxidation (increased isoprostane levels) compared to native glial cells without C26:0 exposure. Furthermore, NAC, TRO, and RSV were capable to mitigate some damages caused by the C26:0 in glial cells. The present work yields experimental evidence that inflammation, oxidative, and nitrative stress may be induced by hexacosanoic acid, the main accumulated metabolite in X-ALD, and that antioxidants might be considered as an adjuvant therapy for this severe neurometabolic disease.
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Acetilcisteína/farmacologia , Cromanos/farmacologia , Ácidos Graxos/farmacologia , Inflamação/patologia , Neuroglia/patologia , Estresse Nitrosativo , Estresse Oxidativo , Rosuvastatina Cálcica/farmacologia , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Vesículas Citoplasmáticas/metabolismo , Dano ao DNA , Interleucina-1beta/metabolismo , Isoprostanos/metabolismo , Neuroglia/metabolismo , Fármacos Neuroprotetores/farmacologia , Nitratos/metabolismo , Nitritos/metabolismo , Estresse Nitrosativo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , RatosRESUMO
Nowadays, chronic kidney disease (CKD) is considered a worldwide public health problem. CKD is a term used to describe a set of pathologies that structurally and functionally affect the kidney, it is mostly characterized by the progressive loss of kidney function. Current therapeutic approaches are insufficient to avoid the development of this disease, which highlights the necessity of developing new strategies to reverse or at least delay CKD progression. Kidney is highly dependent on mitochondrial homeostasis and function, consequently, the idea that mitochondrial pathologies could play a pivotal role in the genesis and development of kidney diseases has risen. Although many research groups have recently published studies of mitochondrial function in acute kidney disease models, the existing information about CKD is still limited, especially in renal mass reduction (RMR) models. This paper focuses on reviewing current experimental information about the bioenergetics, dynamics (fission and fusion processes), turnover (mitophagy and biogenesis) and redox mitochondrial alterations in RMR, to discuss and integrate the mitochondrial changes triggered by nephron loss, as well as its relationship with loss of kidney function in CKD, in these models. Understanding these mechanisms would allow us to design new therapies that target these mitochondrial alterations.
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Mitocôndrias/fisiologia , Insuficiência Renal Crônica/fisiopatologia , Animais , Progressão da Doença , Metabolismo Energético , Humanos , Rim/fisiologia , Renovação Mitocondrial , OxirreduçãoRESUMO
Uvaia (Eugenia pyriformis) is a fruit tree of the Myrtaceae family. It has recalcitrant seeds of limited longevity, making seed propagation difficult. Micropropagation is an alternative method to obtain a large quantity of progeny plants in a short period of time, by using any part of the plant as explant. The high concentration of phenols associated with the chemical composition of the Myrtaceae, and the presence of microorganisms in the plant material or culture media, can make in vitro propagation difficult and/or impossible. The objective was to evaluate various concentrations of antioxidants affecting the control of microbial contamination and phenol oxidation in vitro in uvaia. A completely randomized design was used, with a 3 (antioxidants PVP, L-cysteine, and ascorbic acid) × 3 (antioxidant concentrations 100, 200, and 300 mg L-1) × 2 (activated charcoal at 0 and 2 g L-1) factorial arrangement + 2 additional variables (absence of antioxidants and activated charcoal; absence of antioxidants with 2 g L-1 activated charcoal), with three repetitions comprising four plants each. The percentage of bacterial and fungal contaminations, along with the number of oxidized explants, was evaluated after 7, 14 and 21 days of in vitro cultivation. It was concluded that, where bacterial and fungal contaminations were concerned, in vitro cultivation of uvaia can be performed without the use of antioxidants. PVP or ascorbic acid must, however be used in the process, at a concentration of 300 mg L-1, along with 2 g L-1 of activated charcoal. This helps to minimize phenol oxidation.
A uvaia Eugenia pyriformis é uma frutífera da família das mirtáceas cujas sementes apresentam longevidade curta e aspecto recalcitrante, fato que dificulta a propagação seminífera. A micropropagação surge como alternativa para obtenção de grande quantidade de mudas em curto período de tempo, por meio da utilização de qualquer parte da planta como explante. A elevada concentração de fenóis associados à composição química das mirtáceas e a presença de microrganismos no material vegetal ou no meio de cultura podem dificultar e/ou impossibilitar a propagação in vitro. Objetivou-se avaliar tipos e concentrações de antioxidantes no controle da contaminação microbiana e da oxidação fenólica in vitro de E. pyriformis. Utilizou-se o delineamento inteiramente casualizado em esquema fatorial 3 (antioxidantes PVP, L-cisteína e ácido ascórbico) x 3 (concentrações - 100, 200 e 300 mg L-1) x 2 (carvão ativado 0 e 2 g L-1) + 2 adicionais (ausência de antioxidantes e de carvão ativado; ausência de antioxidantes com 2 g L-1 de carvão ativado), com três repetições constituídas por quatro plantas. Após sete, 14 e 21 dias do cultivo in vitro foram avaliadas a porcentagem de contaminação bacteriana, fúngica e de explantes oxidados. Conclui-se que o cultivo in vitro de E. pyriformis, em relação as contaminações bacterianas e fúngicas, pode ser efetuado sem a utilização de agentes antioxidantes. Entretanto, para reduzir a oxidação fenólica deve ser utilizado o PVP ou ácido ascórbico, ambos na concentração de 300 mg L-1, associados a 2 g L-1 de carvão ativado.
Assuntos
Povidona-Iodo , Ácido Ascórbico , Carvão Vegetal , Myrtaceae , Eugenia , AntioxidantesRESUMO
l-Cysteine is an endogenous sulfur-containing amino acid with multiple and varied roles in the central nervous system, including neuroprotection and the maintenance of the redox balance. However, it was also suggested as an excitotoxic agent implicated in the pathogenesis of neurological disorders such as Parkinson's and Alzheimer's disease. l-Cysteine can modulate the activity of ionic channels, including voltage-gated calcium channels and glutamatergic NMDA receptors, whereas its effects on GABAergic neurotransmission had not been studied before. In the present work, we analyzed the effects of l-cysteine on responses mediated by homomeric GABAA ρ1 receptors, which are known for mediating tonic γ-aminobutyric acid (GABA) responses in retinal neurons. GABAA ρ1 receptors were expressed in Xenopus laevis oocytes and GABA-evoked chloride currents recorded by two-electrode voltage-clamp in the presence or absence of l-cysteine. l-Cysteine antagonized GABAA ρ1 receptor-mediated responses; inhibition was dose-dependent, reversible, voltage independent, and susceptible to GABA concentration. Concentration-response curves for GABA were shifted to the right in the presence of l-cysteine without a substantial change in the maximal response. l-Cysteine inhibition was insensitive to chemical protection of the sulfhydryl groups of the ρ1 subunits by the irreversible alkylating agent N-ethyl maleimide. Our results suggest that redox modulation is not involved during l-cysteine actions and that l-cysteine might be acting as a competitive antagonist of the GABAA ρ1 receptors.
Assuntos
Cisteína/farmacologia , Antagonistas de Receptores de GABA-A/farmacologia , Receptores de GABA-A/efeitos dos fármacos , Animais , Ligação Competitiva , Cloretos/metabolismo , Cistina/farmacologia , Relação Dose-Resposta a Droga , Etilmaleimida/farmacologia , Homocisteína/farmacologia , Humanos , Transporte de Íons/efeitos dos fármacos , Oócitos , Técnicas de Patch-Clamp , RNA Complementar/genética , Receptores de GABA-A/fisiologia , Proteínas Recombinantes/metabolismo , Xenopus laevis , Ácido gama-Aminobutírico/farmacologiaRESUMO
Introduction: Homocysteine (Hcy) tissue accumulation occurs in a metabolic disease characterized biochemically by cystathionine ß-synthase (CBS) deficiency and clinically by mental retardation, vascular problems, and skeletal abnormalities. Previous studies indicate the occurrence of DNA damage secondary to hyperhomocysteinemia and it was observed that DNA damage occurs in leukocytes from CBS-deficient patients. This study aimed to investigate whether an oxidative mechanism could be involved in DNA damage previously found and investigated the in vitro effect of N-acety-L-cysteine (NAC) on DNA damage caused by high Hcy levels. Methods: We evaluated a biomarker of oxidative DNA damage in the urine of CBSdeficient patients, as well as the in vitro effect of NAC on DNA damage caused by high levels of Hcy. Moreover, a biomarker of lipid oxidative damage was also measured in urine of CBS deficient patients. Results: There was an increase in parameters of DNA (8-oxo-7,8-dihydro-2'- deoxyguanosine) and lipid (15-F2t-isoprostanes levels) oxidative damage in CBS-deficient patients when compared to controls. In addition, a significant positive correlation was found between 15-F2t-isoprostanes levels and total Hcy concentrations. Besides, an in vitro protective effect of NAC at concentrations of 1 and 5 mM was observed on DNA damage caused by Hcy 50 µM and 200 µM. Additionally, we showed a decrease in sulfhydryl content in plasma from CBS-deficient patients when compared to controls. Discussion: These results demonstrated that DNA damage occurs by an oxidative mechanism in CBS deficiency together with lipid oxidative damage, highlighting the NAC beneficial action upon DNA oxidative process, contributing with a new treatment perspective of the patients affected by classic homocystinuria.
Assuntos
Humanos , Feminino , Criança , Adolescente , Adulto , Adulto Jovem , Acetilcisteína/farmacologia , Dano ao DNA , Estresse Oxidativo , Cistationina/metabolismo , Desoxiguanosina/urina , Homocistinúria/genética , Antioxidantes/farmacologia , Biomarcadores/urina , Estudos de Casos e Controles , Creatinina/urina , Ensaio Cometa , Cistationina/biossíntese , Cistationina/sangue , Isoprostanos/análise , Desoxiguanosina/análogos & derivados , Homocisteína/sangue , Homocistinúria/sangueRESUMO
ABSTRACT Proteins have been the subject of electrochemical studies. It is possible to apply electrochemical techniques to obtain information about their structure due to the presence of five electroactive amino acids that can be oriented to the outside of the peptidic chain. These amino acids are L-Tryptophan (L-Trp), L-Tyrosine (L-Tyr), L-Histidine (L-His), L-Methionine (L-Met) and L-Cysteine (L-Cys); their electrochemical behavior being subject of extensive research, but it is still controversial. No spectroscopic investigations have been reported on L-Trp, and due to the short life time of the intermediates, ex situ techniques cannot be employed, leading to a never-ending discussion about possible intermediates. In the L-Tyr and L-His cases, spectroelectrochemical studies were performed and different intermediates were observed, suggesting that some intermediates may be observed under specific conditions, as proposed for L-Cys. This amino acid is the most interesting among the electroactive ones because of the presence of a thiol moiety at its side chain, leading to a wide range of oxidation states. It can adsorb onto surfaces of different crystallographic orientation in stereoselective conformation, modifying the surface for different applications.as a surface engineering tool since it plays the role of as an anchor for the growing of nanocrystals inside proteic templates.