RESUMO
The aim of the current study was to determine the activity of the delta-aminolevulinate dehydratase (δ-ALA-D) enzyme, oxidative stress biomarkers and the expression of cytokines in those infected with influenza B virus (IBV). To evaluate the activity of the δ-ALA-D enzyme, lipid peroxidation was estimated as levels of thiobarbituric acid reactive substances, protein and non-protein thiol groups, ferric-reducing antioxidant power (FRAP), vitamin C concentration and cytokine levels in IBV-infected individuals (n = 50) and a control group (n = 30). δ-ALA-D activity was significantly lower in IBV-infected individuals compared with controls, as well as levels of thiols, vitamin C and FRAP. Lipid peroxidation and cytokine levels of IL-6, IL-10, IL-17A and IFN-y were statistically higher in the IBV group. In conclusion, we found evidence of the generation of oxidants, the depletion of the antioxidant system, decrease in the activity of the δ-ALA-D enzyme and an increase in the synthesis of cytokines, thus contributing to a better understanding of oxidative and inflammatory pathways during IBV infection.
Assuntos
Infecções por Herpesviridae , Influenza Humana , Humanos , Antioxidantes , Sintase do Porfobilinogênio/metabolismo , Vírus da Influenza B/metabolismo , Estresse Oxidativo , Ácido Ascórbico , Ferro , Citocinas/metabolismoRESUMO
Lead (Pb) is a metal that can produces irreversible damage in living organisms. Some studies had reported that Pb produces histophysiological alterations in the digestive system (mainly liver) of birds; however, the effect of this metal on small intestine has not been fully examined. Additionally, little information is available on Pb disturbances in native birds of South America. The present study aimed to evaluate the effect of different Pb exposure times on blood δ-aminolevulinic acid dehydratase (δ-ALAD) activity and on the histological and morphometric characteristics of the digestive system (liver and proximal intestine) of eared doves (Zenaida auriculata). A decrease of the blood δ-ALAD activity, dilatation of blood vessels and leukocyte infiltrates in intestinal submucosa and muscular layers, and reduction of the enterocyte nuclear diameter and Lieberkühn crypts area were observed. In liver were noted steatosis, proliferation of bile ducts, dilated sinusoids, leukocyte infiltrates, and melanomacrophage centers. The portal tract area and the thickness of the portal vein wall were increased. In conclusion, the results showed that Pb produces histological and morphometric alterations on the liver and small intestine according to the exposure time, which should be considered when the dangerousness of environmental pollutants is evaluated in wild animals.
Assuntos
Columbidae , Chumbo , Animais , Chumbo/farmacologia , Fígado , América do Sul , Intestinos , Sintase do PorfobilinogênioRESUMO
INTRODUCTION: Oxidative stress is closely related to the pathophysiology of gestation, where the placenta is susceptible to oxidative damage, contributing to the onset of gestational complications. Currently, few studies evaluate the use of oxidative markers for prediction of risk of gestational complications. However, there are some reports that suggest these biomarkers as potential prognostic biomarkers. Therefore, the objective of this study was to compare the biomarkers of oxidative stress from gestations with and without complications, and also evaluate the delta of variation in these markers from the first gestational trimester. MATERIAL AND METHODS: A total of 45 pregnant women were evaluated during the three gestational trimesters, of whom 15 developed gestational complications by the end of gestation. The evaluated oxidative damage markers were thiobarbituric acid reactive substances and nitric oxide dosage. Evaluation of the antioxidant system was performed by the quantification of vitamin C, sulfhydryl groups, total antioxidant capacity, plasmatic iron reduction ability, the evaluation of catalase and delta-aminolevulinate dehydratase enzymatic activity. RESULTS: According to the results, the markers of oxidative damage are increased, and the antioxidant profile decreased, in the third trimester of complicated pregnancies as compared to uncomplicated pregnancies. Moreover, the delta of variation in both oxidative damage markers and antioxidants was higher in complicated gestations as compared to uncomplicated gestations, thus suggesting a higher oxidative stress in pregnancies with complications. CONCLUSIONS: Oxidative stress parameters appear altered in pregnant women with gestational complications. The markers to oxidative stress can be possible biomarkers, helping in understanding mechanisms underlying the associations between complications during pregnancy and various health outcomes.
Assuntos
Antioxidantes , Complicações na Gravidez , Antioxidantes/metabolismo , Ácido Ascórbico , Biomarcadores , Catalase/metabolismo , Feminino , Humanos , Ferro , Óxido Nítrico , Estresse Oxidativo/fisiologia , Sintase do Porfobilinogênio/metabolismo , Gravidez , Gestantes , Substâncias Reativas com Ácido TiobarbitúricoRESUMO
Lolium multiflorum Lam. is a winter weed of difficult control found as diploid (2n) and tetraploid plants (4n). Our study aimed to evaluate the responses of antioxidant enzymes and lipid peroxidation, in both diploid and tetraploid ryegrass varieties. Treatments consisted of control plants (without any herbicide application), and four herbicides with different mechanisms of action. Leaf material was collected 36 h after treatment imposition to determine the lipid peroxidation by ferrous oxidation-xylenol (FOX) content, and the activity of the enzymes superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), glutathione-S-transferase (GST), and δ-aminolevulinic acid dehydratase (ALAD). Both ryegrass varieties showed oxidative stress mainly due to a downregulated decreased (>31%) in SOD activity and an increase (>32%) in lipid peroxidation (FOX), mainly in ryegrass genotypes exposed to haloxyfop, glyphosate, and iodosulfuron. On the other hand, clethodim-treated plants had an increase in SOD and APX activities, associated with a reduced ALAD activity in both 2n (32%) and 4n (11%) genotypes. In general, the 2n genotype was more affected than the 4n genotype.
Assuntos
Herbicidas , Lolium , Antioxidantes/metabolismo , Ascorbato Peroxidases/genética , Catalase/genética , Catalase/metabolismo , Glutationa , Glutationa Transferase/metabolismo , Herbicidas/farmacologia , Peroxidação de Lipídeos , Lolium/genética , Lolium/metabolismo , Estresse Oxidativo , Sintase do Porfobilinogênio , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , TetraploidiaRESUMO
Exposure to lead in environmental and occupational settings continues to be a serious public health problem. At environmentally relevant doses, two mechanisms may underlie lead exposition-induced genotoxicity, disruption of the redox balance and an interference with DNA repair systems. The aim of the study was to evaluate the ability of lead exposition to induce impaired function of Ape1 and its impact on DNA repair capacity of workers chronically exposed to lead in a battery recycling plant. Our study included 53 participants, 37 lead exposed workers and 16 non-lead exposed workers. Lead intoxication was characterized by high blood lead concentration, high lipid peroxidation and low activity of delta-aminolevulinic acid dehydratase (δ-ALAD). Relevantly, we found a loss of DNA repair capacity related with down-regulation of a set of specific DNA repair genes, showing specifically, for the first time, the role of Ape1 down regulation at transcriptional and protein levels in workers exposed to lead. Additionally, using a functional assay we found an impaired function of Ape1 that correlates with high blood lead concentration and lipid peroxidation. Taken together, these data suggest that occupational exposure to lead could decrease DNA repair capacity, inhibiting the function of Ape1, as well other repair genes through the regulation of the ZF-transcription factor, promoting the genomic instability.
Assuntos
Intoxicação por Chumbo , Exposição Ocupacional , Reparo do DNA , Humanos , Chumbo/toxicidade , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Sintase do Porfobilinogênio , ReciclagemRESUMO
Delta-aminolevulinic acid dehydratase (ALAD) enzyme catalyzes the second phase of the heme biosynthesis and is involved in lead toxicokinetics. This research aimed to evaluate its influence on the relationship between blood lead (PbB) levels and intellectual performance in Afro-Brazilian children. PbB, hemoglobin concentration, ALAD activity, and polymorphism were determined in whole blood. Anthropometric, socioeconomic, and family environment stimuli data were collected with appropriate instruments. The non-verbal intelligence of children and their mothers or guardians was assessed using the correspondent Raven's Progressive Matrix versions. The medians (range) of PbB levels and ALAD activity were 1.0 µg/dL (0.1-21.3) and, 71 U/L (31-113), respectively. ALAD G177C was distributed as follows: 97.9% for ALAD1/1 and 2.1% for ALAD1/2 genotypes. The mean of Raven raw score was 19.3 (± 5.6) points and there were no differences according to sex or environmental Pb exposure. No statistically significant association was observed between PbB level and children's IQ. However, ALAD activity presented an inverse significant association with PbB levels, children's percentile IQ, and children's IQ/Age ratio, suggesting a neuroprotective role of ALAD1 genotype in those with low PbB level.
Assuntos
Inteligência , Chumbo , Sintase do Porfobilinogênio , Fatores Sociais , Brasil , Criança , Exposição Ambiental , Etnicidade , Genótipo , Humanos , Chumbo/sangue , Sintase do Porfobilinogênio/genéticaRESUMO
Genetic polymorphisms involved in mercury toxicokinetics and toxicodynamics may be associated with severe mercury toxicity. This study aimed to investigate the impact of an ALAD polymorphism on chronic mercury exposure and the health situation of indigenous children from the Brazilian Amazon. One-hundred-and-three indigenous children (under 15 years old) were included and genotyped (rs1800435) using a TaqMan validated assay. The mean age was 6.6 ± 4.5 years old, 60% were female, 49% presented with anemia, and the mean hair mercury concentration was 7.0 ± 4.5 (1.4-23.9) µg/g, with 49% exceeding the reference limit (≥6.0 µg/g). Only two children were heterozygous ALAD, while the others were all wild type. Minor allele frequency (ALAD G) and heterozygous genotype (ALAD CG) were 1% and 2%, respectively. The two children (12 and 14 years old) with the ALAD polymorphism had mercury levels above the average as well as had neurological symptoms related to chronic mercury exposure, such as visual field alterations, memory deficit, distal neuropathy, and toe amyotrophy. Both children also reported frequent consumption of fish in the diet, at least three times a week. In conclusion, our data confirm that an ALAD polymorphism can contribute to mercury half-life time, harmful effects, and neuropsychological disorders in indigenous children with chronic mercury exposure to gold mining activity.
Assuntos
Mercúrio , Sintase do Porfobilinogênio , Animais , Criança , Pré-Escolar , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Polimorfismo Genético , Sintase do Porfobilinogênio/genéticaRESUMO
Previous studies have shown the porphobilinogen synthase (PBGS) zinc-binding mechanism and its conservation among the living cells. However, the precise molecular interaction of zinc with the active center of the enzyme is unknown. In particular, quantum chemistry techniques within the density functional theory (DFT) framework have been the key methodology to describe metalloproteins, when one is looking for a compromise between accuracy and computational feasibility. Considering this, we used DFT-based models within the molecular fractionation with conjugate caps scheme to evaluate the binding energy features of zinc interacting with the human PBGS. Besides, phylogenetic and clustering analyses were successfully employed in extracting useful information from protein sequences to identify groups of conserved residues that build the ions-binding site. Our results also report a conservative assessment of the relevant amino acids, as well as the benchmark analysis of the calculation models used. The most relevant intermolecular interactions in Zn2+-PBGS are due to the amino acids CYS0122, CYS0124, CYS0132, ASP0169, SER0168, ARG0221, HIS0131, ASP0120, GLY0133, VAL0121, ARG0209, and ARG0174. Among these residues, we highlighted ASP0120, GLY0133, HIS0131, SER0168, and ARG0209 by co-occurring in all clusters generated by unsupervised clustering analysis. On the other hand, the triple cysteines at 2.5 Å from zinc (CYS0122, CYS0124, and CYS0132) have the highest energy attraction and are absent in the taxa Viridiplantae, Sar, Rhodophyta, and some Bacteria. Additionally, the performance of the DFT-based models shows that the processing time-dependence is more associated with the choice of the basis set than the exchange-correlation functional.
Assuntos
Evolução Biológica , Metaloproteínas/química , Metaloproteínas/metabolismo , Sintase do Porfobilinogênio/química , Sintase do Porfobilinogênio/metabolismo , Teoria Quântica , Zinco/metabolismo , Sítios de Ligação , Humanos , Filogenia , Conformação ProteicaRESUMO
Streptozotocin (STZ) is a substance used experimentally to induce a diabetes model, a metabolic disease associated with oxidative tissue damage. This study evaluated if 4-4'-dichloro-diphenyl diselenide (p-ClPhSe)2 modulates oxidative stress in peripheral tissues of diabetic mice. Male Swiss mice received a single STZ injection (i.p.) at a dose of 200 mg/kg or its vehicle and were treated with (p-ClPhSe)2 (7 days, 5 mg/kg) or metformin (200 mg/kg, twice per day). After, the mice were euthanized to collect liver, kidney, and skeletal muscle samples. In the liver, (p-ClPhSe)2 reduced thiobarbituric acid reactive substances (TBARS) and protein carbonyl levels and normalized the superoxide dismutase activity in STZ-treated mice. In the kidney, (p-ClPhSe)2 reversed the increase in the reactive species levels but not the catalase (CAT) activity reduction in STZ-treated mice. There was no evidence of oxidative damage in the skeletal muscle of STZ-treated mice, but an increase in the CAT activity and a reduction in non-protein thiol levels were found. (p-ClPhSe)2 did not reverse a decrease in hepatic and renal δ-aminolevulinic acid dehydratase activity in STZ-treated mice. The results show that the liver and kidney of STZ-treated mice were more susceptible to oxidative stress. This study reveals that (p-ClPhSe)2 modulated oxidative stress, which differently affected peripheral tissues of diabetic mice.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Compostos Organosselênicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Catalase/metabolismo , Diabetes Mellitus Experimental/metabolismo , Rim/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Sintase do Porfobilinogênio/metabolismo , EstreptozocinaRESUMO
BACKGROUND: Acute hepatic porphyrias represent an expanding group of complex inherited metabolic disorders due to inborn errors of metabolism involving heme biosynthesis. OBJECTIVE: We aimed to review the main clinical and therapeutic aspects associated with acute hepatic porphyrias. METHODS: The authors provided a wide non-systematic review of current concepts and recently acquired knowledge about acute hepatic porphyrias. RESULTS: Acute neurovisceral attacks are the most common and life-threatening presentation of this group and are often considered the main clinical manifestation by clinicians during differential diagnosis and the start of proper diagnostic work-up for acute porphyrias. However, atypical presentations with central nervous system involvement, neuropsychiatric disturbances, and some subtypes with photosensitivity usually make the definite diagnosis difficult and late. Early therapeutic interventions are essential during emergency treatment and intercritical periods to avoid recurrent severe presentations. The availability of new disease-modifying therapeutic proposals based on small interfering RNA (siRNA)-based therapies, complementary to the classic intravenous glucose infusion and hemin-based treatments, emphasizes the importance of early diagnosis and genetic counseling of patients. CONCLUSIONS: This review article highlights the main biochemical, pathophysiological, clinical, and therapeutic aspects of acute hepatic porphyrias in clinical practice.
Assuntos
Porfiria Aguda Intermitente , Porfirias Hepáticas , Humanos , Neurologistas , Sintase do Porfobilinogênio , Porfiria Aguda Intermitente/diagnóstico , Porfiria Aguda Intermitente/terapia , RNA Interferente PequenoRESUMO
ABSTRACT Background: Acute hepatic porphyrias represent an expanding group of complex inherited metabolic disorders due to inborn errors of metabolism involving heme biosynthesis. Objective: We aimed to review the main clinical and therapeutic aspects associated with acute hepatic porphyrias. Methods: The authors provided a wide non-systematic review of current concepts and recently acquired knowledge about acute hepatic porphyrias. Results: Acute neurovisceral attacks are the most common and life-threatening presentation of this group and are often considered the main clinical manifestation by clinicians during differential diagnosis and the start of proper diagnostic work-up for acute porphyrias. However, atypical presentations with central nervous system involvement, neuropsychiatric disturbances, and some subtypes with photosensitivity usually make the definite diagnosis difficult and late. Early therapeutic interventions are essential during emergency treatment and intercritical periods to avoid recurrent severe presentations. The availability of new disease-modifying therapeutic proposals based on small interfering RNA (siRNA)-based therapies, complementary to the classic intravenous glucose infusion and hemin-based treatments, emphasizes the importance of early diagnosis and genetic counseling of patients. Conclusions: This review article highlights the main biochemical, pathophysiological, clinical, and therapeutic aspects of acute hepatic porphyrias in clinical practice.
RESUMO Introdução: As porfirias hepáticas agudas representam um grupo de doenças metabólicas hereditárias complexas em expansão, decorrentes de erros inatos do metabolismo, envolvendo a via de biossíntese do grupamento heme. Objetivo: realizar revisão dos principais aspectos clínicos e terapêuticos associados com as porfirias hepáticas agudas. Métodos: Os autores realizaram ampla revisão não-sistemática sobre conceitos atuais e conhecimentos recentemente adquiridos. Resultados: Ataques neuroviscerais agudos representam a apresentação clínica mais comum e de maior risco, e são comumente considerados como principal manifestação na prática clínica durante o diagnóstico diferencial e início apropriado da investigação diagnóstica para porfirias agudas. Entretanto, apresentações atípicas com envolvimento do sistema nervoso central, alterações neuropsiquiátricas e alguns subtipos com fotossensibilidade fazem com que o diagnóstico definitivo seja comumente difícil e tardio. As intervenções terapêuticas precoces são essenciais durante o tratamento emergencial e em período intercrítico evitando formas recorrentes graves. A disponibilidade de novas propostas terapêuticas modificadoras de doença baseadas em terapias com pequenas moléculas de RNA de interferência (siRNA) complementares aos clássicos tratamentos com infusão de glicose intravenosa e à base de hemina enfatiza a importância do diagnóstico precoce de tais pacientes e do aconselhamento genético. Conclusões: Este artigo de revisão destaca os principais aspectos bioquímicos, fisiopatológicos, clínicos e terapêuticos das porfirias hepáticas agudas na prática clínica.
Assuntos
Porfirias Hepáticas , Porfiria Aguda Intermitente/diagnóstico , Porfiria Aguda Intermitente/terapia , RNA Interferente Pequeno , Neurologistas , Sintase do PorfobilinogênioRESUMO
AIMS: The objective of this study was to investigate the effect of the type of delivery (vaginal and cesarean) on the activity of the enzyme delta-aminolevulinate dehydratase (δ-ALA-D), which as yet has not been studied, and the markers of oxidative stress. METHODS: Seventy-six mothers and their newborns were divided into two groups: normal birth (VD) and elective cesarean section (ECS). Samples of maternal and umbilical cord blood were collected up to 5 min after birth. Thiobarbituric acid reactive substances (TBARS), advanced oxidation protein products (AOPP), protein thiol (P-SH), nonprotein (NP-SH), the ferric reducing ability of plasma (FRAP), total antioxidant capacity (TAC), catalase, and δ-ALA-D enzyme activity were tested. RESULTS: TBARS and AOPP were significantly higher in mothers of the VD group, while P-SH, NP-SH, FRAP and TAC were reduced. In newborns, TBARS and AOPP did not differ between the groups; however, in the VD group, there was a decrease in P-SH, NP-SH, FRAP, TAC, and catalase. The activity of the δ-ALA-D enzyme was decreased in mothers and neonates born by VD. CONCLUSIONS: Mothers undergoing VD had higher levels of free radicals and lower antioxidant defenses, while their newborns decreased antioxidant defenses likely to contain the oxidative imbalance. The inhibition of the δ-ALA-D enzyme in this scenario allows its use as a useful marker of oxidative stress in different obstetric settings.
Assuntos
Cesárea , Sintase do Porfobilinogênio , Antioxidantes , Feminino , Humanos , Recém-Nascido , Estresse Oxidativo , Sintase do Porfobilinogênio/metabolismo , Gravidez , Substâncias Reativas com Ácido TiobarbitúricoRESUMO
In this study, we evaluated the usefulness of nondestructive biomarkers approach in giant toads (Rhinella marina). We obtained blood samples and the residual condition index of toads from rural and industrial zones from Coatzacoalcos River, Mexico (COA). In the blood samples, we determined the activity of enzymes, lipid peroxidation, and the presence of cell death (apoptosis). We found that the activity of the enzyme delta-aminolevulinic dehydratase was lower. Still, the glutathione s-transferase activity and the percentage of apoptosis in erythrocytes were higher in the toads of COA than laboratory toads. Meanwhile, some biomarkers in toads showed differences when compared between Industrial and Rural zones. These results and correlations between biomarkers showed how the response changed in the toads living near the industrial zones. We demonstrate that a nondestructive biomarkers approach can be useful in environmental studies with anuran amphibians.
Assuntos
Bufo marinus , Poluentes da Água/toxicidade , Animais , Apoptose , Biomarcadores/sangue , Butirilcolinesterase/sangue , Eritrócitos/efeitos dos fármacos , Feminino , Glutationa Transferase/sangue , Masculino , Malondialdeído/sangue , México , Sintase do Porfobilinogênio/sangue , RiosRESUMO
This study evaluated the toxic effects of inorganic mercury (Hg) in pregnant and lactating rats, as well as the possible protective effect of zinc (Zn) and N-acetylcysteine (NAC). Pregnant and lactating rats were pre-treated with ZnCl2 (27 mg/kg) and/or NAC (5 mg/kg) and after 24 h, they were exposed to HgCl2 (10 mg/kg). Animals were sacrificed 24 h after Hg exposure, and biochemical tests and metal determination were performed. Regarding pregnant rats, Hg exposure caused kidney, blood, and placenta δ-aminolevulinic acid dehydratase (δ-ALA-D) activity inhibition, and the pre-treatments showed a tendency of protection. Moreover, all the animals exposed to Hg presented high Hg levels in the kidney, liver, and placenta when compared with control group. Pregnant rats pre-exposed to Zn (Zn-Hg and Zn/NAC-Hg groups) presented an increase in hepatic metallothionein levels. Therefore, lactating rats exposed to Hg presented renal and blood δ-ALA-D inhibition; the pre-treatments showed a tendency to prevent the renal δ-ALA-D inhibition and prevented the blood δ-ALA-D inhibition caused by Hg. Lactating rats exposed to Hg presented high Hg levels in the kidney and liver. These results showed that 10 mg/kg of HgCl2 causes biochemistry alterations in pregnant and lactating rats, and Zn and NAC present promising results against these damages.
Assuntos
Acetilcisteína , Mercúrio , Acetilcisteína/farmacologia , Animais , Feminino , Rim , Lactação , Fígado , Cloreto de Mercúrio/toxicidade , Mercúrio/toxicidade , Sintase do Porfobilinogênio , Gravidez , Ratos , ZincoRESUMO
Autism is a neuropathology characterized by behavioral disorders. Considering that oxidative stress is involved in the pathophysiology of this disease, we evaluated the effects of quercetin, a flavonoid with antioxidant and neuroprotective properties, in an experimental model of autism induced by valproic acid (VPA). Twelve pregnant female rats were divided into four groups (control, quercetin, VPA, and VPA+quercetin). Quercetin (50 mg/kg) was administered orally to the animals from gestational days 6.5 to 18.5, and VPA (800 mg/kg) was administered orally in a single dosage on gestational day 12.5. Behavioral tests such as open field, social interaction, and tail flick nociceptive assays were performed on pups between 30 and 40 days old, after which the animals were euthanized. Cerebral cortex, hippocampus, striatum, and cerebellum were collected for evaluation of oxidative stress parameters. The pups exposed to VPA during the gestational period showed reduced weight gain, increased latency in the open field and tail flick tests, reduced time of social interaction, accompanied by changes in oxidative stress parameters mainly in the hippocampus and striatum. Prenatal treatment with quercetin prevented the behavioral changes and damage caused by oxidative stress, possibly due to its antioxidant action. Our findings demonstrated that quercetin has neuroprotective effects in an animal model of autism, suggesting that this natural molecule could be an important therapeutic agent for treatment of autism spectrum disorders (ASDs).
Assuntos
Transtorno Autístico/prevenção & controle , Transtorno Autístico/psicologia , Química Encefálica , Sintase do Porfobilinogênio/metabolismo , Quercetina/uso terapêutico , Animais , Anticonvulsivantes , Transtorno Autístico/induzido quimicamente , Feminino , Atividade Motora , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo , Medição da Dor , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos , Ratos Wistar , Interação Social , Ácido Valproico , Aumento de PesoRESUMO
Lead intoxication can generate pro-inflammatory conditions that have been proposed to be associated with cell injuries and oxidative stress. The pro-inflammatory state can participate in the pathophysiology of this toxicity to generate immune response dysfunctions, which could condition the presence of clinical manifestations and susceptibility to infections already described in lead-exposed patients. In the present work, we study workers of a battery recycler factory (nâ¯=â¯24) who are chronically exposed to lead and compared them with non-lead exposed workers (nâ¯=â¯17). Lead-exposed workers had high lead concentrations in blood (med 69.8 vs. 1.7⯵g/dL), low δ-ALAD activity (med 149 vs. 1100â¯nmol PBG/h/mL), high lipid peroxidation (med 0.86 vs. 0.69â¯nmol/mL) and high erythrocytes apoptosis (med 0.81 vs. 0.50% PS externalization) in relation to non-lead exposed workers. Also, lead-exposed workers had a high incidence of signs and symptoms related to lead intoxication and a higher frequency of infections. The higher leukocyte apoptosis (med 18.3 vs. 8.2% PS externalization) and lower basal TNF-α concentration (med 0.38 vs. 0.94â¯pg/mL) in lead-exposed workers imply an immune response dysfunction; however, there was no difference in the TNF-α concentration when leukocytes were stimulated with lipopolysaccharide in whole blood (med 44 vs. 70â¯pg/mL), suggesting that lead-exposed workers might develop adaptation mechanisms to reduce basal TNF-α release through downregulation processes proposed for this cytokine.
Assuntos
Apoptose/efeitos dos fármacos , Intoxicação por Chumbo/patologia , Leucócitos/patologia , Exposição Ocupacional , Fator de Necrose Tumoral alfa/sangue , Adulto , Estudos de Casos e Controles , Eritrócitos/patologia , Feminino , Humanos , Imunidade/efeitos dos fármacos , Chumbo/sangue , Peroxidação de Lipídeos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Sintase do Porfobilinogênio/sangueRESUMO
Purpose: To assess and understand the maternal oxidative stress in twin pregnancies, currently not studied, through ascertain indicators of oxidative damage in maternal blood in response of two fetuses, as well as the relation of placenta with or without the increase of oxidative stress in these gestations.Materials and methods: The activity of delta-aminolevulinate dehydratase (δ-ALA-D) was analyzed as an indirect marker of oxidative stress, as well as the quantification of thiobarbituric acid reactive substances (TBARS), protein thiol groups (P-SH) and nonprotein thiol groups (NP-SH), vitamin C (VIT C) and catalase activity (CAT) in maternal blood samples from twin (n = 30) and single (n = 30) pregnancies. This study was approved by the Human Ethics Committee UFSM (register by the number 49823015.4.0000.5346).Results: TBARS was significantly higher in twin pregnancies, while thiol groups, VIT C and CAT were decreased, asides from the reduced activity of δ-ALA-D in comparison to single fetus gestations.Conclusions: The study established an oxidative stress increased and an antioxidant ability decreased in twin pregnancies, suggesting a possible relation between the levels of oxidants and antioxidants with the complications in those gestations.
Assuntos
Sintase do Porfobilinogênio , Gravidez de Gêmeos , Antioxidantes , Ácido Ascórbico , Catalase/metabolismo , Estresse Oxidativo , Sintase do Porfobilinogênio/metabolismo , Substâncias Reativas com Ácido TiobarbitúricoRESUMO
The purpose is to determine markers of oxidative stress related to the longer and shorter duration of labor (DOL) of pregnant women in the umbilical cord blood of neonates, not yet studied. Blood samples from the umbilical cord were collected from pregnant women with normal delivery and classified according to DOL in two groups: a group with DOL less than 310 min (n = 33) and a group with DOL greater than or equal to 310 min (n = 35). The oxidative stress parameters were analyzed by the quantification of thiobarbituric acid reactive substances (TBARS), nitrate/nitrite (NOx), protein thiol groups (P-SH) and non-protein (NP-SH), vitamin C and plasma iron reduction capacity (FRAP), in addition to the activity of the enzyme delta-aminolevulinate dehydratase (δ-ALA-D). The activity of the δ-ALA-D enzyme was shown to be decreased in longer DOL, however, the oxidant parameters and antioxidants were higher in the longer DOL, with the exception of NP-SH that was lower. The longer maternal DOL time is related to the alteration of δ-ALA-D enzyme activity and other parameters in neonates, suggesting an increase in the passage of maternal oxidative markers by umbilical cord blood.
Assuntos
Biomarcadores/sangue , Sangue Fetal/metabolismo , Trabalho de Parto/fisiologia , Estresse Oxidativo/fisiologia , Sintase do Porfobilinogênio/metabolismo , Adolescente , Adulto , Antioxidantes/análise , Ácido Ascórbico/sangue , Feminino , Humanos , Recém-Nascido , Óxido Nítrico/sangue , Sintase do Porfobilinogênio/sangue , Gravidez , Compostos de Sulfidrila/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Fatores de Tempo , Adulto JovemRESUMO
Purpose: Determining the post-mortem interval (PMI) is one of the challenging tasks in forensic science due to the lack of quick and inexpensive methods. Our objective is to develop innovative and alternative means for PMI evaluation. Methods: The relationship between PMI and enzymatic modifications in mice tissues was described. After being sacrificed, Swiss mice were randomly divided into groups according to the time elapsed since death. The activities of catalase (CAT) and δ-aminolevulinate dehydratase (δ-ALA-D) were determined in hepatic, renal, skeletal muscle and cerebral tissues. Results: CAT activity increased in kidney and brain 6 h after death and this increase remained for up to 24 h in the brain and 48 h in the kidney. δ-ALA-D had its activity decreased in the liver and kidneys in 6 h. In the skeletal muscle, δ-ALA-D activity was reduced only 48 h after death. Conversely, an increase on δ-ALA-D activity was observed in the brain at 6 h, followed by its decrease at 24 and 48 h. Conclusion: With the association of this set of results, it is possible to provide an estimate of PMI. Additionally, these results can be used as an auxiliary parameter associated with other methods to estimate PMI.
Assuntos
Catalase , Sintase do Porfobilinogênio , Mudanças Depois da Morte , Animais , Autopsia , Catalase/metabolismo , Cérebro/enzimologia , Ensaios Enzimáticos , Rim/enzimologia , Fígado/enzimologia , Camundongos , Músculo Esquelético/enzimologia , Sintase do Porfobilinogênio/metabolismo , Fatores de TempoRESUMO
The increment of eryptosis in lead-exposed workers has been associated with oxidative stress, having as the main mediator [Ca2+]i. However, other molecules could participate as signals, such as PLA2 and SMase, which have been proposed to increase PGE2 and ceramides, both involved in the increment of PS externalization due to osmotic stress. To study the role of these enzymes in lead intoxication, we studied 30 lead exposed workers and 27 non-lead exposed individuals. We found, compared to non-exposed subjects, lead intoxication characterized by high blood lead concentration (medianâ¯=â¯39.1⯵g/dL), and low δ-ALAD activity (medianâ¯=â¯348â¯nmol of porphobilinogen/h/mL); oxidative stress with high lipid peroxidation (medianâ¯=â¯1.31â¯nmol of malondialdehyde/mL) and low TAC (medianâ¯=â¯370â¯mM Trolox equivalents); a higher enzymatic activity of PLA2 (medianâ¯=â¯518 AFU/mg) and SMase (medianâ¯=â¯706 AFU/mg) and higher eryptosis (medianâ¯=â¯0.92% PS externalization). Correlation and conditional probability analyses permit to associate oxidative stress and eryptosis with high PLA2 activity. However, high SMase activity was only associated with PLA2 activity. The role of these enzymes in the signal path to eryptosis induced by oxidative stress in lead-exposed workers is discussed.