Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 13 de 13
Filtrar
1.
Toxicol Lett ; 400: 35-41, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39117292

RESUMO

Lead (Pb2+) is one of the most common toxic metals present in the environment, and lead exposure causes serious health issues in humans. Lead is widely used because of its physio-chemical characteristics, which include softness, corrosion resistance, ductility, and low conductivity. Lead affects almost all human organs, specifically the central nervous system. Lead neurotoxicity is connected to various neural pathways, including brain-derived neurotrophic factor (BDNF) protein level alterations, cyclic adenosine 3',5'-monophosphate (cAMP) response element binding protein (CREB) pathway changes, and N-methyl-D-aspartate receptors (NMDARs) changes. Lead primarily affects protein kinase C (PKC) through the replacement of calcium (Ca2+) ions in the CREB pathway. In this review, we have discussed the effect of lead on the CREB pathway and its implications on the nervous system, highlighting its effects on learning, synaptic plasticity, memory, and cognitive deficits. This review provides an understanding of the lead-induced alterations in the CREB pathway, which can lead to the future prospect of its use as a diagnostic marker as well as a therapeutic target for neurodegenerative disorders.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Chumbo , Doenças Neurodegenerativas , Humanos , Chumbo/toxicidade , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/induzido quimicamente , Animais , Transdução de Sinais/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos
2.
Toxicology ; 503: 153771, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38452865

RESUMO

Lead (Pb2+) is a hazardous heavy metal that is pervasive in the human environment as a result of anthropogenic activity, and poses serious health risks, particularly in children. Due to its innumerable unique physical and chemical properties, it has various applications; therefore, it has become a common environmental pollutant. Lead may cause oxidative stress, and accumulating evidence indicates that oxidative stress influences the pathophysiology of lead poisoning, also called plumbism. The immune system is continually exposed to various environmental pathogens and xenobiotics, including heavy metals such as lead, and appears to be one of the most vulnerable targets. After being exposed to lead, cells are subjected to oxidative stress as a result of reactive oxygen species (ROS) production. When the generation and consumption of ROS are out of equilibrium, various cell structures, particularly phospholipids are disrupted leading to lipid peroxidation. Various inflammatory signalling pathways are activated as a consequence, along with reduced disease resistance, inflammation, autoimmunity, sensitization and disruption of the cell-mediated and humoral immune systems. Lead negatively affects the metabolism of cytokines, including the interleukins IL-2, IL-1b, IL-6, IL-4, IL-8, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN), as well as the expression and functioning of inflammatory enzymes such as cyclooxygenases. However, the cause of toxicity depends on the kind of lead, dosage, route of entry, exposure period, age, host and genetic predisposition.


Assuntos
Poluentes Ambientais , Intoxicação por Chumbo , Metais Pesados , Criança , Humanos , Citocinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Chumbo/toxicidade , Metais Pesados/toxicidade , Poluentes Ambientais/toxicidade , Estresse Oxidativo
3.
Toxicol Res (Camb) ; 12(2): 178-188, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37125327

RESUMO

Lead (Pb2+) poisoning is a public health concern of global dimensions. Although several public health guidelines and workplace safety policies are existing and enforced, lead toxicity cases are drastically increasing. Lead exposure leads to numerous harmful consequences and causes adverse effects on different body organs and systems, mainly via the generation of reactive oxygen species, leading to augmented oxidative stress, competing with metal ions, and binding with the sulfhydryl groups. In several instances, lead poisoning cases remain undiagnosed and untreated or receive only symptomatic treatment. Estimation of blood lead levels reflects only a recent exposure, however, which does not reveal the total body burden. This review summarizes the effects of lead with special reference to hepatotoxicity and some of the potential diagnostic biomarkers. Furthermore, it also focuses on synthetic chelators used in the treatment of lead poisoning and the advantage of using bioactive compounds with an emphasis on the ameliorative effect of garlic.

4.
Mol Biol Rep ; 50(6): 5465-5479, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37155010

RESUMO

Organophosphate pesticides (OPs) are widely used in agriculture, healthcare, and other industries due to their ability to kill pests. However, OPs can also have genotoxic effects on humans who are exposed to them. This review summarizes the research on DNA damage caused by OPs, the mechanisms behind this damage, and the resulting cellular effects. Even at low doses, OPs have been shown to damage DNA and cause cellular dysfunction. Common phenomena seen in cells that are exposed to OPs include the formation of DNA adducts and lesions, single-strand and double-strand DNA breaks, and DNA and protein inter and intra-cross-links. The present review will aid in comprehending the extent of genetic damage and the impact on DNA repair pathways caused by acute or chronic exposure to OPs. Additionally, understanding the mechanisms of the effects of OPs will aid in correlating them with various diseases, including cancer, Alzheimer's, and Parkinson's disease. Overall, knowledge of the potential adverse effects of different OPs will help in monitoring the health complications they may cause.


Assuntos
Inseticidas , Intoxicação por Organofosfatos , Praguicidas , Humanos , Praguicidas/toxicidade , Organofosfatos/toxicidade , Reparo do DNA , Dano ao DNA
5.
Neurotox Res ; 40(5): 1539-1552, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35781222

RESUMO

Pesticides have been used in agriculture, public health programs, and pharmaceuticals for many decades. Though pesticides primarily target pests by affecting their nervous system and causing other lethal effects, these chemical entities also exert toxic effects in inadvertently exposed humans through inhalation or ingestion. Mounting pieces of evidence from cellular, animal, and clinical studies indicate that pesticide-exposed models display metabolite alterations of pathways involved in neurodegenerative diseases. Hence, identifying common key metabolites/metabolic pathways between pesticide-induced metabolic reprogramming and neurodegenerative diseases is necessary to understand the etiology of pesticides in the rise of neurodegenerative disorders. The present review provides an overview of specific metabolic pathways, including tryptophan metabolism, glutathione metabolism, dopamine metabolism, energy metabolism, mitochondrial dysfunction, fatty acids, and lipid metabolism that are specifically altered in response to pesticides. Furthermore, we discuss how these metabolite alterations are linked to the pathogenesis of neurodegenerative diseases and to identify novel biomarkers for targeted therapeutic approaches.


Assuntos
Doenças Neurodegenerativas , Praguicidas , Animais , Biomarcadores/metabolismo , Encéfalo/metabolismo , Dopamina , Ácidos Graxos , Glutationa/metabolismo , Humanos , Metaboloma , Doenças Neurodegenerativas/induzido quimicamente , Praguicidas/toxicidade , Triptofano/metabolismo
6.
Drug Chem Toxicol ; 45(6): 2483-2487, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34334063

RESUMO

The deficiency of essential minerals increases lead absorption and thus aggravates the lead-induced toxic effects. This study was aimed at understanding the ameliorative effect of essential minerals on lead-induced alterations in hematological parameters in rats. To achieve this objective, the study was conducted in 320 male Wistar albino rats, grouped into two, with equal numbers. One of the groups of rats was fed on a mineral-supplemented food referred to as a 'well-nourished group' and another group 'undernourished group' on food without mineral supplements. Each group of rats was further subdivided into 'Subjects' and 'Controls.' Subjects of both the groups of rats were exposed to 500 ppm lead acetate up to a period of 300 days (10 months) in drinking water and the role of minerals on lead-induced alterations in hematological parameters was evaluated. A significant decrease (p < 0.001) in hemoglobin (Hb) and δ-aminolevulinic acid dehydratase (δ-ALAD) levels and a significant increase (p < 0.001) in urinary δ-aminolevulinic acid (δ-ALAU) levels were seen in subjects without mineral supplementation compared to those fed on a mineral-enriched diet. A positive correlation was observed between blood lead levels (PbB) and δ-ALAU (r = 0.792) and a negative correlation with Hb (r = -0.926) and δ-ALAD (r = -0.836) in the subjects. These changes were very prominent in the undernourished subjects when compared to the well-nourished subjects. Observations of the present study indicate that mineral supplementation with ongoing lead exposure may help in minimizing the absorption of lead and reduce lead-induced toxic effects.


Assuntos
Chumbo , Minerais , Animais , Masculino , Ratos , Acetatos , Ácido Aminolevulínico , Hemoglobinas , Chumbo/toxicidade , Minerais/farmacologia , Sintase do Porfobilinogênio , Ratos Wistar
7.
Toxicol Lett ; 353: 13-19, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34626817

RESUMO

Lead (Pb) is an environmental and public health toxicant. It affects various organ systems of the body, thereby disrupting their normal functions. To date, several genes that are known to influence the mechanism of action of lead and toxicity have been studied. Among them, the iron transporter gene, SLC11A2 (Solute Carrier 11 group A member 2) which codes for the transmembrane protein, DMT1 (Divalent Metal Transporter 1) has shown to transport other metals including zinc, copper, and lead. We investigated the influence of DMT1 polymorphism (rs224589) on blood lead (Pb-B) levels. In the present study, we enrolled 113 lead-exposed workers and performed a comprehensive biochemical analysis and genetic composition. The frequency of DMT1 variants observed in the total subjects (n = 113) was 42 % for homozygous CC wild type, 54 % for heterozygous CA, and 4 % for homozygous AA mutant. The heterozygous CA carriers presented higher Pb-B levels compared to wild type CC and mutant AA carriers. Further, a negative association was observed between Pb-B levels and hemoglobin in heterozygous CA carriers. Hence, C allele may be the risk allele that contributes to increased susceptibility to high Pb-B retention, and genotyping of DMT1 in lead exposed subjects might be used as a prognostic marker to impede organ damage due to lead toxicity.


Assuntos
Proteínas de Transporte de Cátions/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Chumbo/sangue , Adolescente , Adulto , Idoso , Proteínas de Transporte de Cátions/genética , Poluentes Ambientais/sangue , Humanos , Ferro/metabolismo , Pessoa de Meia-Idade , Exposição Ocupacional , Polimorfismo de Nucleotídeo Único , Adulto Jovem
8.
Environ Sci Pollut Res Int ; 28(16): 19643-19663, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33666848

RESUMO

Bisphenol A [BPA; (CH3)2C(C6H4OH)2] is a synthetic chemical used as a precursor material for the manufacturing of plastics and resins. It gained attention due to its high chances of human exposure and predisposing individuals at extremely low doses to diseases, including cancer. It enters the human body via oral, inhaled, and dermal routes as leach-out products. BPA may be anticipated as a probable human carcinogen. Studies using in vitro cell lines, rodent models, and epidemiological analysis have convincingly shown the increasing susceptibility to cancer at doses below the oral reference dose set by the Environmental Protection Agency for BPA. Furthermore, BPA exerts its toxicological effects at the genetic and epigenetic levels, influencing various cell signaling pathways. The present review summarizes the available data on BPA and its potential impact on cancer and its clinical outcome.


Assuntos
Disruptores Endócrinos , Compostos Benzidrílicos/toxicidade , Carcinógenos/toxicidade , Fenóis/toxicidade
9.
Hum Exp Toxicol ; 40(6): 897-914, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33233953

RESUMO

Lead is a ubiquitous heavy metal toxin of significant public health concern. Every individual varies in their response to lead's toxic effects due to underlying genetic variations in lead metabolizing enzymes or proteins distributed in the population. Earlier studies, including our lab, have attributed the influence of ALAD (δ-Aminolevulinate dehydratase) polymorphism on blood lead retention and ALAD activity. The present study aimed to investigate the influence of VDR (Vitamin D receptor) and HFE (Hemochromatosis) polymorphisms in modulating blood lead levels (BLLs) of occupationally exposed workers. 164 lead-exposed subjects involved in lead alloy manufacturing and battery breaking and recycling processes and 160 unexposed controls with BLLs below 10 µg/dL recruited in the study. Blood lead levels, along with a battery of biochemical assays and genotyping, were performed. Regression analysis revealed a negative influence of BLLs on ALAD activity (p < 0.0001) and a positive influence on smokeless tobacco use (p < 0.001) in lead-exposed subjects. A predicted haplotype of the three VDR polymorphisms computed from genotyping data revealed that T-A-A haplotype increased the BLLs by 0.93 units (p ≤ 0.05) and C-C-A haplotype decreased the BLLs by 7.25 units (p ≤ 0.05). Further analysis revealed that the wild-type CC genotype of HFE H63D presented a higher median BLL, indicating that variant C allele may have a role in increasing the concentration of lead. Hence, the polymorphism of genes associated with lead metabolism might aid in predicting genetic predisposition to lead and its associated effects.


Assuntos
Proteína da Hemocromatose/efeitos dos fármacos , Intoxicação por Chumbo/sangue , Intoxicação por Chumbo/genética , Chumbo/sangue , Exposição Ocupacional/efeitos adversos , Polimorfismo Genético , Receptores de Calcitriol/efeitos dos fármacos , Adulto , Feminino , Predisposição Genética para Doença , Proteína da Hemocromatose/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Calcitriol/metabolismo
10.
Toxicol Lett ; 335: 11-27, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32949623

RESUMO

Lead is a toxin of great public health concern affecting the young and aging population. Several factors such as age, gender, lifestyle, dose, and genetic makeup result in interindividual variations to lead toxicity mainly due to variations in metabolic consequences. Hence, the present study aimed to examine dose-dependent lead-induced systemic changes in metabolism using rat model by administering specific doses of lead such as 10 (low lead; L-Pb), 50 (moderate lead; M-Pb), and 100 mg/kg (high lead; H-Pb) body weight for a period of one month. Biochemical and haematological analysis revealed that H-Pb was associated with low body weight and feed efficiency, low total protein levels (p ≤ 0.05), high blood lead (Pb-B) levels (p ≤ 0.001), low ALAD (δ-aminolevulinate dehydratase) activity (p ≤ 0.0001), high creatinine (p ≤ 0.0001) and blood urea nitrogen (BUN) (p ≤ 0.01) levels, elevated RBC and WBC counts, reduced haemoglobin and blood cell indices compared to control. Spatial learning and memory test revealed that H-Pb exposed animals presented high latency to the target quadrant and escape platform compared to other groups indicating H-Pb alters cognition function in rats. Histopathological changes were observed in liver and kidney as they are the main target organs of lead toxicity. LC-MS analysis further revealed that Butyryl-L-carnitine (p ≤ 0.01) and Ganglioside GD2 (d18:0/20:0) (p ≤ 0.05) levels were significantly reduced in H-Pb group compared to all groups. Further, pathway enrichment analysis revealed abundance and significantly modulated metabolites associated with oxidative stress pathways. The present study is the first in vivo model of dose-dependent lead exposure for serum metabolite profiling.


Assuntos
Rim/efeitos dos fármacos , Intoxicação por Chumbo/metabolismo , Chumbo/toxicidade , Fígado/efeitos dos fármacos , Nitratos/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Rim/metabolismo , Rim/patologia , Chumbo/sangue , Intoxicação por Chumbo/sangue , Intoxicação por Chumbo/fisiopatologia , Fígado/metabolismo , Fígado/patologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Metabolômica , Nitratos/sangue , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
11.
Toxicol Ind Health ; 36(5): 346-355, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32496147

RESUMO

Lead is a nonessential metal which enters the body through various means and is considered as one of the most common health toxins. Several cases of lead poisoning are reported as a result of inhalation or ingestion of lead in employees working as painters, smelters, electric accumulator manufacturers, compositors, auto mechanics, and miners. In addition to occupational lead exposure, several cases of lead poisoning are reported in the general population through various sources and pathways. Innumerable signs and symptoms of lead poisoning observed are subtle and depend on the extent and duration of exposure. The objective of this review article is to discuss occupationally and nonoccupationally exposed lead poisoning cases reported in India and the associated symptoms, mode of therapy, and environmental intervention used in managing these cases. Lead poisoning cases cannot be identified at an early stage as the symptoms are very general and mimic that of other disorders, and patients might receive only symptomatic treatment. Knowledge about the various symptoms and potential sources is of utmost importance. Medical practitioners when confronted with patients experiencing signs and symptoms as discussed in this article can speculate the possibility of lead poisoning, which could lead to early diagnosis and its management.


Assuntos
Exposição Ambiental/efeitos adversos , Intoxicação por Chumbo/diagnóstico , Intoxicação por Chumbo/etiologia , Terapia por Quelação/métodos , Cosméticos/efeitos adversos , Exposição Ambiental/análise , Feminino , Humanos , Índia , Intoxicação por Chumbo/sangue , Masculino , Doenças Profissionais/diagnóstico , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos
12.
Mitochondrion ; 48: 60-66, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31029642

RESUMO

Lead is a public health hazard substance affecting millions of people worldwide especially those who are occupationally exposed. Our study aimed to investigate the effect of occupational lead exposure on mitochondria DNA (mtDNA). By sequencing the whole mitochondria genome, we identified 25 unique variants in lead exposed subjects affecting 10 protein coding genes in the order of MT-ND1, MT-ND2, MT-CO2, MT-ATP8, MT-ATP6, MT-CO3, MT-ND3, MT-ND4, MT-ND5, and MT-CYB. Mitochondria functional analysis revealed that exposure to lead can reduce reactive oxygen species (ROS) levels, alter mitochondria membrane potential (MMP) and increase mitochondrial mass (MM). This was further supported by mtDNA copy number analysis which was increased in lead exposed individuals compared to unexposed control group indicating the compensatory mechanism that lead has in stabilizing the mitochondria. This is the first report of mtDNA mutation and copy number analysis in occupationally lead exposed subjects where we identified mtDNA mutation signature associated with lead exposure thus providing evidence for altered molecular mechanism to compensate mitochondrial oxidative stress.


Assuntos
Genoma Mitocondrial/efeitos dos fármacos , Genoma Mitocondrial/genética , Chumbo/efeitos adversos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Mutação/efeitos dos fármacos , Mutação/genética , Adulto , DNA Mitocondrial/genética , Genes Mitocondriais/efeitos dos fármacos , Genes Mitocondriais/genética , Humanos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/genética , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Espécies Reativas de Oxigênio/metabolismo
13.
Ind Health ; 47(6): 677-80, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19996545

RESUMO

Lead (Pb) is widely used because of its useful properties and it is ubiquitous in human environment. There are various lead based industries and several workers who are working in these industries without the knowledge of the ill effects of lead and hence not taking proper precautions while handling lead. Many a times, these workers who have accumulated lead in their blood and body organs, are not properly diagnosed and might receive only symptomatic treatment. We describe a thirty-two-year old male, who was working in an unorganized lead based industry for 3 yr, developed severe lead poisoning leading to wrist drop. Since one year the patient received only symptomatic treatment for abdominal pain. His laboratory investigation showed elevated blood lead levels. The chelation therapy using D-Penicillamine brought down his blood lead levels and is on follow up presently. It is required to take proper history about the occupation of the patient, exposed to potentially hazardous levels of lead in the workplace and medically evaluate them.


Assuntos
Intoxicação por Chumbo/complicações , Doenças Profissionais/complicações , Exposição Ocupacional/efeitos adversos , Neuropatia Radial/etiologia , Adulto , Quelantes/uso terapêutico , Humanos , Intoxicação por Chumbo/diagnóstico , Intoxicação por Chumbo/tratamento farmacológico , Masculino , Doenças Profissionais/diagnóstico , Doenças Profissionais/tratamento farmacológico , Neuropatia Radial/tratamento farmacológico , Punho/inervação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA