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1.
Cell Physiol Biochem ; 58: 336-360, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39092511

RESUMO

BACKGROUND/AIMS: Individual resistance to hypoxia is an important feature of the physiological profile of an organism, particularly in relation to lead-induced toxicity. METHODS: Our study focused on evaluating parameters of mitochondrial oxygen consumption, microsomal oxidation, intensity of lipoperoxidation processes and antioxidant defences in the liver of rats with low (LR) and high (HR) resistance to hypoxia to elucidate the mechanisms of action of L-arginine and the NO synthase inhibitor L-NNA before or after exposure to lead nitrate. RESULTS: Our study suggests that the redistribution of oxygen-dependent processes towards mitochondrial processes under the influence of the nitric oxide precursor amino acid L-arginine is an important mechanism for maintaining mitochondrial respiratory chain function during per os lead nitrate exposure (3.6 mg lead nitrate/kg bw per day for 30 days). Animals were given L-arginine at a dose of 600 mg/kg bw (i.p., 30 min) before and after exposure to lead nitrate or the NO synthase inhibitor Nω-nitro-L-arginine (L-NNA) at a dose of 35 mg/kg bw (i.p., 30 min) before and after exposure to lead nitrate. Our experiments demonstrated the efficacy of using lead nitrate to simulate lead-related toxic processes via Pb levels in liver tissue; we demonstrated significantly reduced levels of nitrites and nitrates, i.e. stable metabolites of the nitric oxide system, in both LR and HR animals. The effect of the amino acid L-arginine stabilised the negative effects of lead nitrate exposure in both groups of LR and HR rats. We observed the efficiency of mitochondrial energy supply processes and showed a greater vulnerability of NADH-dependent oxidation during lead nitrate exposure in the liver of HR rats. CONCLUSION: L-arginine initiated the processes of oxidation of NADH-dependent substrates in the LR group, whereas in the HR group this directionality of processes was more effective when the role of the nitric oxide system was reduced (use of L-NNA). Our study of key antioxidant enzyme activities in rat liver tissue during lead nitrate exposure revealed changes in the catalase-peroxidase activity ratio. We found different activities of antioxidant enzymes in the liver tissue of rats treated with lead nitrate and L-arginine or L-NNA, with a significant increase in GPx activity in the LR group when L-arginine was administered both before and after exposure to lead nitrate.


Assuntos
Arginina , Hipóxia , Chumbo , Nitratos , Nitroarginina , Ratos Wistar , Animais , Arginina/metabolismo , Arginina/farmacologia , Nitratos/metabolismo , Masculino , Ratos , Nitroarginina/farmacologia , Hipóxia/metabolismo , Chumbo/toxicidade , Fígado/metabolismo , Fígado/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Catalase/metabolismo
2.
Ecotoxicol Environ Saf ; 274: 116194, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38479312

RESUMO

Lead (Pb) is one of the most dreadful non-essential elements whose toxicity has been well reported worldwide due to its interference with the major plant functions and its overall yield. Bioremediation techniques comprising the application of beneficial microorganisms have gained attention in recent times owing to their ecofriendly nature. Addition of organic matter to soil has been reported to stimulate microbial activities. Compost application improves soil structure and binds toxic contaminants due to its larger surface area and presence of functional groups. Furthermore, it stimulates soil microbial activities by acting as C-source. So, in current study, we investigated the individual and synergistic potential of two lead (Pb)-tolerant Pseudomonas strains alongwith compost (1% w/w) in sustaining sunflower growth under Pb contaminated soil conditions. Lead chloride (PbCl2) salt was used for raising desired Pb concentration (500 mg kg-1). Results revealed that Pb stress drastically affected all the measured attributes of sunflower plant, however joint application of rhizobacteria and compost counteracted these adverse effects. Among them, co-application of str-1 and compost proved to be significantly better than str-2, as its inoculation significantly improved shoot and root lengths (64 and 76%), leaf area and leaves plant-1 (95 and 166%), 100-achene weight (200%), no. of flowers plant-1 (138%), chl 'a', 'b' and carotenoid (86, 159 and 33%) contents in sunflower as compared to control treatments. Furthermore, inoculation of Pseudomonas fluorescens along with compost increased the NPK in achene (139, 200 and 165%), flavonoid and phenolic contents (258 and 185%) along with transpiration and photosynthetic rates (54 and 72%) in leaves as compared to control treatment under Pb contamination. In addition, Pb entry to roots, shoots and achene were significantly suppressed under by 87, 90 and 91% respectively due to integrated application of compost and str-1 as evident by maximum Pb-immobilization efficiency (97%) obtained in this treatment. Similarly, bioconcentration factors for roots, shoots and achene were found to be 0.58, 0.18 and 0.0055 with associated translocation factor (0.30), which also revealed phytostabilization of Pb under combined application of PGPR and compost. Since, phytoremediation of heavy metals under current scenario of increasing global population is inevitable, results of the current study concluded that tolerant PGPR species along with organic amendments such as compost can inhibit Pb uptake by sunflower and confer Pb tolerance via improved nutrient uptake, physiology, antioxidative defense and gas exchange.


Assuntos
Compostagem , Helianthus , Poluentes do Solo , Antioxidantes/metabolismo , Helianthus/metabolismo , Pseudomonas/metabolismo , Chumbo/toxicidade , Chumbo/metabolismo , Biodegradação Ambiental , Raízes de Plantas/metabolismo , Solo/química , Nutrientes , Poluentes do Solo/análise
3.
World J Microbiol Biotechnol ; 40(2): 74, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38246905

RESUMO

Heavy metal pollution is a global issue. Current study provides evidence on Pb toxicity ameliorative potential and safe nature of Levilactobacillus brevis MZ384011 (S1) and Levilactobacillus brevis MW362779 (S2), isolated from carnivore gut and human milk, respectively. In a 60-days experiment, the rats were distributed into six groups. G-I, G-V and G-VI were kept on normal diet, while GII-IV were fed on lead nitrate (500 mg/kg) supplemented food, throughout experiment. After confirmation of Pb toxicity in GII-IV at 15th day, S1 was orally administered to G-III and G-V while S2 was given to G-IV and G-VI at a dose of 1 × 109 CFU/animal/day. On day 60 of experiment, positive control (G-II) displayed significant reduction in body weight, total protein, albumin, globulin, mineral profile, erythrocyte count, hemoglobin, hematocrit and hematological indices and elevation in leukocyte count, alanine aminotransferase, aspartate aminotransferase, bilirubin, uric acid and creatinine along with alterations in hepato-renal architecture. With reference to G-II, the G-III and G-IV displayed significant improvement in all aforementioned parameters, 40-60% reduction in tissue Pb levels (blood, liver, kidney and adipose tissue) and elevation in fecal Pb contents (p = 0.000). The groups V and VI did not show any sign of toxicity. The findings confirm that strains are safe for biological application and can reverse Pb toxicity by facilitating fecal Pb excretion and reducing its systemic dispersal. To best of our information this is the first report on Pb toxicity ameliorative role of Levilactobacillus brevis from human milk, the safest source.


Assuntos
Levilactobacillus brevis , Humanos , Animais , Ratos , Chumbo/toxicidade , Fígado , Poluição Ambiental , Fezes
4.
J Bioenerg Biomembr ; 55(1): 79-89, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36637735

RESUMO

Exposure to the environmental pollutant lead (Pb) has been linked to Alzheimer's disease (AD), in which mitochondrial dysfunction is a pathological consequence of neuronal degeneration. The toxicity of Pb in combination with ß-amyloid peptides (1-40) and (25-35) causes selective death in neuronal cells. However, the precise mechanism through which Pb induces Alzheimer's disease, particularly mitochondrial damage, is unknown. Changes in mitochondrial mass, membrane potential, mitochondrial complex activities, mitochondrial DNA and oxidative stress were examined in neuronal cells of human origin exposed to Pb and ß-amyloid peptides (1-40) and (25-35) individually and in different combinations. The results showed depolarization of mitochondrial membrane potential, decrease in mitochondrial mass, ATP levels and mtDNA copy number in Pb and ß-amyloid peptides (1-40) and (25-35) exposed cells. Also, significant reductions in the expression of mitochondrial electron transport chain (ETC) complex proteins (ATP5A, COXIV, UQCRC2, SDHB, NDUFS3), as well as down regulation of ETC complex gene expressions such as COXIV, ATP5F1 and NDUFS3 and antioxidant gene expressions like MnSOD and Gpx4 were observed in exposed cells. Furthermore, Pb and ß-amyloid peptides exposure resulted in elevated mitochondrial malondialdehyde levels and a decrease in mitochondrial GSH levels. Our findings suggest that Pb toxicity could be one of the causative factors for the mitochondrial dysfunction and oxidative stress in Alzheimer's disease progression.


Assuntos
Doença de Alzheimer , Poluentes Ambientais , Humanos , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/toxicidade , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Chumbo/metabolismo , Poluentes Ambientais/metabolismo , Estresse Oxidativo/fisiologia , Mitocôndrias/metabolismo
5.
BMC Vet Res ; 19(1): 45, 2023 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-36765350

RESUMO

BACKGROUND: Water pollutants cause adverse effects in aquatic ecosystems. The immunomodulatory and mitigating effects of dietary 1,3-glucan on fipronil and lead-induced intoxication in African catfish (Clarias gariepinus) were investigated. Two hundred forty catfish were randomly divided into four equal groups: those in the first group were fed basic diet and served as controls; those in the second group were supplemented with ß-1,3-glucan (0.1%); those in the third group were exposed to combination of lead nitrate at 0.041 mg/L (1/10 96 h LC50) and fipronil at 2.8 mg/l (1/10 96 h LC50); and those in the fourth group were exposed to combination of fipronil, lead, and ß-1,3-glucan. The health status, haematological, immunological, and histological changes were all evaluated. RESULT: Swelling on the dorsolateral side, spinal column deviation, sluggish movement, skin bleaching, excessive mucus secretion, significant variations in blood indices-related measures, and a 45% death rate were observed in the third group. There was a significant reduction in interleukin-1 (IL-1) and interleukin-6 (IL-6) and immunoglobulin M (IgM) concentrations, as well as decrease in their corresponding gene expression, indicating that fipronil and lead had immunosuppressive activity. Severe catarrhal enteritis and mucinous degeneration of the lining epithelium, and notable depletion of white pulp, congested red pulp and hemosiderosis were common pathological findings in the spleen. ß-1,3-glucan alone or in combination with fipronil and lead provoked physical activity, blood indices, with elevations in IL-1ß, IL-2, IL-6, and IgM concentrations, as well as up-regulation in their genes' expression in splenic tissues, when compared to the third group. The spleen and intestine had normal histological architecture with 5% mortalities. There were no fish deaths in the ß-1,3-glucan-alone or control groups. CONCLUSION: The use of ß-1,3-glucan (0.1%) as dietary supplement could be implemented to protect against the toxic effects of fipronil and lead toxicity by improving the health and immunological parameters of intoxicated catfish.


Assuntos
Peixes-Gato , Poluentes Ambientais , Condicionamento Físico Animal , Poluentes Químicos da Água , Animais , Glucanos/metabolismo , Chumbo/toxicidade , Chumbo/metabolismo , Poluentes Ambientais/metabolismo , Ecossistema , Interleucina-6/metabolismo , Poluentes Químicos da Água/metabolismo
6.
Int Arch Occup Environ Health ; 96(10): 1333-1347, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37804366

RESUMO

OBJECTIVE: Globally millions of people working in various industries and are exposed to different toxins which may affect their genetic stability and DNA integrity. Present study was designed to estimate the expression variation of genes related to DNA repair (XRCC1, PARP1) and lead toxicity (ALAD) in exposed industrial workers. METHODS: About 200 blood samples were collected from workers of brick kiln, welding, furniture and paint industry (50/industry) along with age and gender matched controls. mRNA expression of genes was measured using RT-PCR. Serum levels of total ROS, POD, TBAR activity was calculated. Blood lead levels were estimated by atomic absorption spectrometer. RESULTS: Relative expression of XRCC1 and PARP1 gene was significantly (P < 0.001) upregulated, while ALAD gene expression was downregulated in exposed group compared to control. Expression of XRCC1 and PARP1 was increased (P < 0.001) in exposed workers with > 30 year age compared to control with > 30 year age. Same was observed when < 30 year age group of control and exposed was compared. Likewise, XRCC1 and PARP1 expression was increased (P < 0.001) in exposed workers with > 30 year age compared to workers with < 30 year age. Whereas, ALAD gene showed significant (P < 0.01) decrease in > 30 year age workers compared to control of same age and exposed with < 30 year of age. Relative expression of XRCC1 and PARP1 was increased (P < 0.001) in exposed smokers compared to exposed non-smokers and control smokers. Whereas, ALAD gene expression reduced (P < 0.001) significantly in both groups. Blood lead content was higher (P < 0.001) in exposed group compared to control. Strong correlation was observed between XRCC1, PARP1 and ALAD gene versus age, total exposure duration, exposure per day and lead deposition. ROS, TBARS and POD activity was higher (P < 0.01) in exposed group compared to control group. CONCLUSION: Present study suggested deregulation of genes related to DNA repair and lead intoxication in exposed group compared to controls. Strong correlation was observed between selected genes and demographic parameters. Present results revealed altered activity of oxidative stress markers which would induce oxidative damage to DNA integrity and limit the function of repair enzymes.


Assuntos
Intoxicação por Chumbo , Exposição Ocupacional , Humanos , Chumbo , Espécies Reativas de Oxigênio , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Reparo do DNA/genética , Intoxicação por Chumbo/genética , DNA , Dano ao DNA , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética
7.
Toxicol Ind Health ; 39(5): 281-289, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37073565

RESUMO

Lead shielding is used as a guard against scatter radiation. Lead aprons can emit particulate lead into the occupational environment, resulting in the accumulation of lead dust on the skin and garments of workers. This study aimed to assess the risk of lead exposure among radiologists working in the radiology departments by estimating hair and blood lead levels. A total of 40 radiology personnel (18 wearing aprons and 22 not wearing aprons) with a comparable control group (20 personnel not working in a radiology department) underwent a pre-designed questionnaire with estimation of blood and hair levels. The hair and blood lead levels in radiologists wearing aprons were significantly higher than those of the control group and that of the radiologist not wearing aprons. The lead levels in hair and blood were correlated significantly with the duration of wearing aprons in years and weekly working hours. Health care workers in radiology departments demonstrated high hair and blood levels that were higher among workers wearing aprons than those not wearing protective equipment. Hair lead levels can be detected quickly, cheaply, and non-invasively, and could be a helpful screening test for occupational exposure.


Assuntos
Exposição Ocupacional , Radiologia , Humanos , Chumbo , Doses de Radiação , Egito , Medição de Risco , Hospitais , Exposição Ocupacional/análise
8.
Toxicol Ind Health ; 39(7): 356-363, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37178329

RESUMO

High blood levels of lead have been shown to relate to its toxicity, and its early detection in occupational workers is important to take necessary measures. The genes associated with lead toxicity were identified by in silico analysis of expression profile (GEO-GSE37567) based on lead exposure of peripheral blood mononuclear cells maintained in culture. The GEO2R tool was used to identify differentially expressed genes (DEGs) among three groups: control versus day-1 treatment, control versus day-2 treatment, and control versus day-1 treatment versus day-2 treatment, and their enrichment analysis was performed to categorize them for molecular function, biological process, cellular component, and KEGG pathways. The protein-protein interaction (PPI) network of DEGs was constructed using a STRING tool and hub genes were identified by using the CytoHubba plugin of Cytoscape. Top 250 DEGs were screened in the first and second groups and 211 DEGs were in the third group. Fifteen critical genes viz. MT1G, ASPH, MT1F, TMEM158, CDK5RAP2, BRCA2, MT1E, EDNRB, MT1H, KITLG, MT1X, MT2A, ARRDC4, MT1M, and MT1HL1 were selected for functional enrichment and pathway analysis. The DEGs were primarily enriched in metal ion binding, metal absorption, and cellular response to metal ions. The significantly enriched KEGG pathways included mineral absorption, melanogenesis, and cancer signaling pathways. PPI network analysis revealed that seven genes of the MT family exhibited good connectedness and served as a marker of lead induced toxicity. Our study suggests that MT1E, MT1H, MT1G, MT1X, MT1F, MT1M, and MT2A of the metallothioneins gene family may act as potential biomarkers to monitor lead exposure.


Assuntos
Perfilação da Expressão Gênica , Chumbo , Humanos , Chumbo/toxicidade , Leucócitos Mononucleares , Mapas de Interação de Proteínas/genética , Metalotioneína/genética , Biologia Computacional , Proteínas de Membrana/genética , Proteínas Supressoras de Tumor/genética , Proteínas do Tecido Nervoso/genética , Proteínas de Ciclo Celular/genética
9.
Toxicol Appl Pharmacol ; 434: 115794, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34780723

RESUMO

BACKGROUND: Discrepancies are present in the findings from clinical trials evaluating a physiological role of iron status in the lead-exposed population. OBJECTIVE: The purpose of this article was to summarize the current understanding of cellular mechanisms of lead toxicity and present a comprehensive review of existing clinical trials related to associations of lead poisoning and iron status. Although an association of iron metabolism pathways that are affected by lead intoxication has been studied, there are still aspects that remain to be elucidated. The existence of additional Pb uptake pathways besides DMT1 transporter-mediated is postulated to non-specifically regulate lead absorption. METHODS: Authors performed a systematic search of PubMed, EMBASE® and Web of Science databases to identify studies that reported an association between health risks of non-organic lead that are associated with iron status markers as possible effect modifier. RESULTS: There were 58 studies that met the pre-defined inclusion criteria for the systematic review. There is a strong body of evidence supporting the hypothesis that alleviated blood lead level can be correlated with a reduced body iron store and increasing the risk of anemia. This association is of a high significance in cases of a young adolescent, weaker in groups of older children and often without a statistical significance in adults. DISCUSSION: Discrepancies in the observations may result from different specificities of lead absorption pathways in children and adults, as well as the power of the statistical tests in varying population sizes. It may be assumed that the extent of iron deficits coupled together with source, timing, and severity of lead exposure, significantly influence the correlation between these factors. Some of the intervention programs of counteracting lead poisoning by iron supplementation proved to be effective and may be a promising prevention strategy for the exposed population.


Assuntos
Poluentes Ambientais/toxicidade , Ferro/metabolismo , Chumbo/toxicidade , Interações Medicamentosas , Exposição Ambiental , Humanos , Ferro/farmacocinética , Chumbo/farmacocinética , Exposição Ocupacional
10.
Biometals ; 35(1): 1-25, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35048237

RESUMO

Lead (Pb) is a multimedia contaminant with various pathophysiological consequences, including cognitive decline and neural abnormalities. Recent findings have reported an association of Pb toxicity with Alzheimer's disease (AD). Studies have revealed that mitochondrial dysfunction is a pathological characteristic of AD. According to toxicology reports, Pb promotes mitochondrial oxidative stress by lowering complex III activity in the electron transport chain, boosting reactive oxygen species formation, and reducing the cell's antioxidant defence system. Here, we review recent advances in the role of mitochondria in Pb-induced AD pathology, as well as the mechanisms associated with the mitochondrial dysfunction, such as the depolarisation of the mitochondrial membrane potential, mitochondrial permeability transition pore opening; mitochondrial biogenesis, bioenergetics and mitochondrial dynamics alterations; and mitophagy and apoptosis. We also discuss possible therapeutic options for mitochondrial-targeted neurodegenerative disease (AD).


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides , Antioxidantes , Humanos , Chumbo/toxicidade , Mitocôndrias/patologia , Doenças Neurodegenerativas/patologia
11.
Environ Res ; 204(Pt B): 112115, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34563525

RESUMO

Lead is one of the highly toxic heavy metals causes various diseases even at very lower concentrations to human and affects eco-system. It is mainly released into the water through industrial activities. Phytoremediation is useful to degrade, reduce, metabolize and assimilate lead from wastewater. In this study, Turbinaria ornata was collected from the sea and dried biomass was used for biosorption of heavy metals. Adsorption of heavy metal was maximum after 100 min incubation with alga powder at acidic pH (4.5). The interactive effects of lead concentration, contact times, pH, biomass concentration and agitation speed was evaluated by a two-level full factorial design. Initial lead concentration, agitation speed and biomass concentration were the most important variables affecting lead removal (p < 0.001) were selected for optimization using central composite rotatable design. Lead removal was found to be maximum (99.8%) in optimized conditions: initial lead 99.8 mg/L, 250 rpm agitation speed and 16.2 g/L biomass concentrations. Municipal wastewater was collected and lead concentration (0.013 mg/L) and physiochemical factors were analyzed. Algal biomass removed >98.5% lead form the wastewater within 10 min in an optimized condition. The present study confirmed the potential application of T. ornata for the removal of lead from contaminated environment.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Adsorção , Biodegradação Ambiental , Biomassa , Resíduos Perigosos , Humanos , Concentração de Íons de Hidrogênio , Águas Residuárias
12.
Doc Ophthalmol ; 145(1): 71-76, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35691959

RESUMO

PURPOSE: To describe a case of presumed retinal lead poisoning. METHODS: Clinical examination, optical coherence tomography, fundus autofluorescence, fluorescein angiography, and electroretinography were used to study a 42-year-old male with the complaint of bilateral reduced vision following systemic lead poisoning. RESULTS: The fundus examination showed venous tortuosity, as well as macular atrophy, and pigmentary changes in his both eyes. Optical coherence tomography revealed retinal thinning, outer retinal and retinal pigment epithelium atrophy, as well as foveal schitic changes. Blue autofluorescence showed moderately hypoautofluorescence in peripapillary area of both eyes. Fluorescein angiogram showed a leopard-like pattern of hypo- and hyperfluorescence in the posterior pole. Electroretinogram showed a moderate reduction in photopic and scotopic responses. CONCLUSIONS: The most probable diagnosis of this case is early onset retinal lead poisoning.


Assuntos
Intoxicação por Chumbo , Degeneração Retiniana , Adulto , Eletrorretinografia , Angiofluoresceinografia , Humanos , Intoxicação por Chumbo/diagnóstico , Masculino , Degeneração Retiniana/induzido quimicamente , Degeneração Retiniana/diagnóstico por imagem , Tomografia de Coerência Óptica
13.
Ecotoxicol Environ Saf ; 231: 113200, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35051762

RESUMO

Lead (Pb) is a widespread environmental pollutant which is a toxic threat to human and animal health. The present study was designed to evaluate the ameliorative role of quercetin in laying quails exposed to Pb. A total of 112 birds were randomly divided into four groups. The control group was fed with basal diet, the Pb group was fed with ration supplemented with Pb at the dose of 100 mg/kg (as Pb (II) acetate trihydrate), the Quercetin group was fed with ration supplemented with quercetin at the dose of 400 mg/kg, and the Pb+ Quercetin group was fed with ration supplemented with Pb at the dose of 100 mg/kg and quercetin at dose of 400 mg/kg. Results showed that serum total protein, glucose, albumin, and blood urea nitrogen (BUN) values of the Pb + Quercetin group partially improved with quercetin supplementation. Meanwhile, serum creatinine values of the Pb + Quercetin group was found to be significantly lower than that of the Pb group. Aspartate aminotransferase (AST) and alanine transaminase (ALT) enzyme activities in the Quercetin and Pb + Quercetin groups were similar to those of the Control group, unlike the Pb group. Moreover, alkaline phosphatase (ALP) enzyme activity of the Pb + Quercetin group significantly improved with the addition of quercetin. We also found that malondialdehyde (MDA) levels of the kidney, liver, and heart were significantly reduced by quercetin supplementation. The glutathione, catalase, and glutathione peroxidase activities of the kidney, liver, and heart tissue were increased by quercetin supplementation. These results were in line with the observed apoptotic markers. The expression of caspase-3 and caspase-9 were significantly decreased by quercetin supplementation. It may be concluded that dietary supplementation with quercetin ameliorates the toxic effects of Pb exposure by alleviating oxidative stress, biochemical changes, and apoptosis in quails.


Assuntos
Coturnix , Quercetina , Animais , Antioxidantes/metabolismo , Apoptose , Coturnix/metabolismo , Dieta , Humanos , Chumbo/metabolismo , Chumbo/toxicidade , Fígado/metabolismo , Estresse Oxidativo , Quercetina/farmacologia
14.
J Am Soc Nephrol ; 32(10): 2425-2434, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34266982

RESUMO

BACKGROUND: Although patients with kidney disease may be particularly susceptible to the adverse health effects associated with lead exposure, whether levels of lead found commonly in drinking water are associated with adverse outcomes in patients with ESKD is not known. METHODS: To investigate associations of lead in community water systems with hemoglobin concentrations and erythropoietin stimulating agent (ESA) use among incident patients with ESKD, we merged data from the Environmental Protection Agency (EPA) Safe Drinking Water Information System (documenting average 90th percentile lead concentrations in community water systems during 5 years before dialysis initiation, according to city of residence) with patient-level data from the United States Renal Data System. RESULTS: Among 597,968 patients initiating dialysis in the United States in 2005 through 2017, those in cities with detectable lead levels in community water had significantly lower pre-ESKD hemoglobin concentrations and more ESA use per 0.01 mg/L increase in 90th percentile water lead. Findings were similar for the 208,912 patients with data from the first month of ESKD therapy, with lower hemoglobin and higher ESA use per 0.01 mg/L higher lead concentration. These associations were observed at lead levels below the EPA threshold (0.015 mg/L) that mandates regulatory action. We also observed environmental inequities, finding significantly higher water lead levels and slower declines over time among Black versus White patients. CONCLUSIONS: This first nationwide analysis linking EPA water supply records to patient data shows that even low levels of lead that are commonly encountered in community water systems throughout the United States are associated with lower hemoglobin levels and higher ESA use among patients with advanced kidney disease.


Assuntos
Água Potável/química , Hematínicos/uso terapêutico , Hemoglobinas/metabolismo , Falência Renal Crônica/sangue , Chumbo/análise , Negro ou Afro-Americano , Idoso , Bases de Dados Factuais , Água Potável/legislação & jurisprudência , Eritropoese , Feminino , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Registro Médico Coordenado , Pessoa de Meia-Idade , Diálise Renal , Estados Unidos , United States Environmental Protection Agency , Abastecimento de Água/legislação & jurisprudência , População Branca
15.
Drug Chem Toxicol ; 45(4): 1606-1613, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33280449

RESUMO

Lead is a common environmental toxicant associated greatly with hematological and hormonal imbalance, biochemical alterations, and reproductive abnormalities. This study was conducted to evaluate the effects of D-ribose-L-cysteine (DRLC) on hematobiochemical and reproductive toxicity associated with lead acetate exposure in adult female Wistar rats. Thirty-two adult female Wistar rats (165 ± 20 g) were divided into four groups (n = 8). Group A received normal saline as placebo; Group B received 100 mg/kg BW of lead acetate only; Group C received 100 mg/kg BW of lead acetate and 10 mg/kg BW DRLC (low dose); Group D received 100 mg/kg BW of lead acetate and 30 mg/kg BW of DRLC (high dose). All administration was done via oral gavage for 42 days, thereafter animals were sacrificed; serum was obtained from the blood collected for analysis, ovaries, and uterus was harvested for analysis. The lead acetate only group showed a significant difference in hematological indices relative to control. Additionally, there was a significant decrease in body weight, sodium dismutase, catalase, reduced glutathione, progesterone with a corresponding increase in ovarian weight, MDA, FSH, and LH among the lead acetate only group relative to the control. Histological observation showed atretic antral follicles, with detached granulosa cells, pyknotic nuclei in the granulosa wall in the ovaries of the lead-exposed only group compared to the control. Co-administration of DRLC and lead attenuate the toxicity of lead exposure by restoring the hematological values, biochemical parameters, hormone profile, and morphology of the ovary. Exposure to lead acetate causes deleterious toxicity to hematological and reproductive functions which were ameliorated DRLC supplementation through its antioxidant mechanisms.


Assuntos
Chumbo , Ovário , Acetatos/toxicidade , Animais , Cisteína/análogos & derivados , Feminino , Chumbo/metabolismo , Chumbo/toxicidade , Ovário/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , Tiazolidinas
16.
Molecules ; 27(3)2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35164259

RESUMO

The use of natural products as therapeutic agents is rapidly growing recently. In the current study, we investigated the protective effects of green tea supplementation on lead-induced toxicity in mice. Forty albino mice were divided into four groups as follows: A: control group; B: green tea receiving group; C: lead-intoxicated group; and D: lead-intoxicated group supplemented with green tea. At the end of the experiment, the animals were tested for neurobehavioral and biochemical alterations. Green tea was analyzed through Gas Chromatography-Mass Spectrometry (GC/MS) analysis. We found that supplementation with green tea ameliorated the lead-associated increase in body weight and blood glucose. Green tea supplementation also changed the blood picture that was affected due to lead toxicity and ameliorated lead-induced dyslipidemia. The group of mice that were supplemented with green tea has shown positive alterations in locomotory, anxiety, memory, and learning behaviors. The GC/MS analysis revealed many active ingredients among which the two most abundant were caffeine and 1,2-benzenedicarboxylic acid, mono(2-ethylhexyl) ester. We concluded that green tea supplementation has several positive effects on the lead-induced neurotoxicity in mice and that these effects may be attributed to its main two active ingredients.


Assuntos
Intoxicação do Sistema Nervoso por Chumbo/prevenção & controle , Chumbo/toxicidade , Chá , Animais , Comportamento Animal/efeitos dos fármacos , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Encéfalo/metabolismo , Dislipidemias/induzido quimicamente , Dislipidemias/prevenção & controle , Cromatografia Gasosa-Espectrometria de Massas/métodos , Chumbo/sangue , Chumbo/metabolismo , Camundongos
17.
Toxicol Mech Methods ; 32(8): 559-568, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35300571

RESUMO

Exposure to lead (Pb), an environmental pollutant, is closely associated with the development of neurodegenerative disorders through oxidative stress induction and alterations in mitochondrial function. Damaged mitochondria could be one of the reasons for the progression of Alzheimer's Disease (AD). Mitophagy is vital in keeping the cell healthy. To know its role in Pb-induced AD, we investigated the PINK1/Parkin dependent pathway by studying specific mitophagy marker proteins such as PINK1 and Parkin in differentiated SH-SY5Y cells. Our data have indicated a significant reduction in the levels of PINK1 and Parkin in cells exposed to Pb and ß-amyloid peptides, both Aß (25-35) and Aß (1-40) individually and in different combinations, resulting in defective mitophagy. Also, the study unravels the status of mitochondrial permeability transition pore (MPTP), mitochondrial mass, mitochondrial membrane potential (MMP) and mitochondrial ROS production in cells treated with individual and different combination of Pb and Aß peptides. An increase in mitochondrial ROS production, enhanced MPTP opening, depolarization of membrane potential and reduced mitochondrial mass in the exposed groups were observed. Also, in the present study, we found that Pb and ß-amyloid peptides could trigger apoptosis by activating the Bak protein, which releases the cytochrome c from mitochondria through MPTP that further activates the AIF (apoptosis inducing factor) and caspase-3 proteins in the cytosol. The above findings reveal the potential role of mechanisms like PINK1/Parkin mediated mitophagy and dysfunctional mitochondria mediated apoptosis in Pb induced neurotoxicity.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides/metabolismo , Neuroblastoma , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Apoptose , Humanos , Chumbo/toxicidade , Mitofagia/fisiologia , Proteínas Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
18.
Appl Environ Microbiol ; 87(20): e0100521, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34347513

RESUMO

The physical environments in which microorganisms naturally reside rarely have homogeneous structure, and changes in their porous architecture may have effects on microbial activities that are not typically captured in conventional laboratory studies. In this study, to investigate the influence of environmental structure on microbial responses to stress, we constructed structured environments with different pore properties (determined by X-ray computed tomography). First, using glass beads in different arrangements and inoculated with the soil yeast Saitozyma podzolica, increases in the average equivalent spherical diameters (ESD) of a structure's porous architecture led to decreased survival of the yeast under a toxic metal challenge with lead nitrate. This relationship was reproduced when yeasts were introduced into additively manufactured lattice structures, comprising regular arrays with ESDs comparable to those of the bead structures. The pore ESD dependency of metal resistance was not attributable to differences in cell density in microenvironments delimited by different pore sizes, supporting the inference that pore size specifically was the important parameter in determining survival of stress. These findings highlight the importance of the physical architecture of an organism's immediate environment for its response to environmental perturbation, while offering new tools for investigating these interactions in the laboratory. IMPORTANCE Interactions between cells and their structured environments are poorly understood but have significant implications for organismal success in both natural and nonnatural settings. This work used a multidisciplinary approach to develop laboratory models with which the influence of a key parameter of environmental structure-pore size-on cell activities can be dissected. Using these new methods in tandem with additive manufacturing, we demonstrated that resistance of yeast soil isolates to stress (from a common metal pollutant) is inversely related to pore size of their environment. This has important ramifications for understanding how microorganisms respond to stress in different environments. The findings also establish new pathways for resolving the effects of physical environment on microbial activity, enabling important understanding that is not readily attainable with traditional bulk sampling and analysis approaches.


Assuntos
Basidiomycota/efeitos dos fármacos , Chumbo/toxicidade , Nitratos/toxicidade , Poluentes do Solo/toxicidade , Resistência a Medicamentos , Porosidade , Solo
19.
J Biochem Mol Toxicol ; 35(8): e22816, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34043862

RESUMO

The present study was conducted to investigate the potential adverse effect of Pb on pregnant Sprague-Dawley rats and their fetuses after maternal exposure, on gestational days (GD) 7-16. The possible protective role of taurine (TA), administered throughout the gestation period (GD 1-20) against Pb toxicity, was also evaluated. Pregnant rats were divided into four groups: Group 1 (control) was given distilled water; Group 2 was exposed to Pb (250 ppm) in drinking water (GD 7-16), whereas Group 3 received TA (50 mg/kg/day) by oral gavage (GD 1-20); Group 4 was exposed to Pb (GD 7-16), whereas pretreated with TA from GD 1 till the end of the gestation period. After termination on GD 20, maternal and embryo-fetal outcomes were evaluated. Blood samples were collected for hematological and biochemical parameters assessment. The results showed that, Pb induced a significant reduction in the maternal body weight, weight gain, uterine and placental weight, in addition to a high incidence of abortion and fetal resorption. Meanwhile, fetuses demonstrated decreased body weight and length, with a high rate of mortality as well as external and skeletal abnormalities. Additionally, Pb induced severe hematological and biochemical alterations in both dams and fetuses. The toxicity of Pb was further emphasized by placental histopathological examination and hepatic DNA fragmentation. Pretreatment with TA greatly attenuated the impact of Pb on both maternal and fetal parameters. Moreover, TA alleviated the incidence of placental damage and hepatic DNA fragmentation. The results highlight the potential prophylaxis role of TA against maternal and developmental Pb toxicity.


Assuntos
Chumbo/toxicidade , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Taurina/farmacologia , Animais , Feminino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Ratos , Ratos Sprague-Dawley
20.
Arch Toxicol ; 95(8): 2643-2657, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34165617

RESUMO

N,N'-bis(2-mercaptoethyl)isophthalamide (NBMI) is a novel lipophilic heavy metal chelator and thiol redox antioxidant. This study was designed to investigate the neuroprotective activity of NBMI in U-87 MG cells exposed to lead acetate (PbAc). Cells were pretreated with NBMI for 24 h prior to a 48 h exposure to PbAc. Cell death (55%, p < 0.0001) and reduction of intracellular GSH levels (0.70-fold, p < 0.005) induced by 250 µM Pb were successfully attenuated by NBMI pretreatment at concentrations as low as 10 µM. A similar pretreatment with the FDA-approved Pb chelator dimercaptosuccinic acid (DMSA) proved ineffective, indicating a superior PKPD profile for NBMI. Pretreatment with NBMI successfully counteracted Pb-induced neuroinflammation by reducing IL-1ß (0.59-fold, p < 0.05) and GFAP expression levels. NBMI alone was also found to significantly increase ferroportin expression (1.97-fold, p < 0.05) thereby enhancing cellular ability to efflux heavy metals. While no response was observed on the apoptotic pathway, this study demonstrated for the first time that necrotic cell death induced by Pb in U-87 MG cells is successfully attenuated by NBMI. Collectively these data demonstrate NBMI to be a promising neuroprotective compound in the realm of Pb poisoning.


Assuntos
Derivados de Benzeno/farmacologia , Quelantes/farmacologia , Fármacos Neuroprotetores/farmacologia , Compostos Organometálicos/toxicidade , Compostos de Sulfidrila/farmacologia , Proteínas de Transporte de Cátions/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Glioblastoma/patologia , Humanos , Doenças Neuroinflamatórias/etiologia , Doenças Neuroinflamatórias/prevenção & controle , Succímero/farmacologia
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