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1.
Ecotoxicol Environ Saf ; 191: 110159, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31962214

RESUMO

Mercury chloride (HgCl2) is a chemical pollutant widely found in the environment. This form of mercury is able to promote several damages to the Central Nervous System (CNS), however the effects of HgCl2 on the spinal cord, an important pathway for the communication between the CNS and the periphery, are still poorly understood. The aim of this work was to investigate the effects of HgCl2 exposure on spinal cord of adult rats. For this, animals were exposed to a dose of 0.375 mg/kg/day, for 45 days. Then, they were euthanized, the spinal cord collected and we investigated the mercury concentrations in medullary parenchyma and the effects on oxidative biochemistry, proteomic profile and tissue structures. Our results showed that exposure to this metal promoted increased levels of Hg in the spinal cord, impaired oxidative biochemistry by triggering oxidative stress, mudulated antioxidant system proteins, energy metabolism and myelin structure; as well as caused disruption in the myelin sheath and reduction in neuronal density. Despite the low dose, we conclude that prolonged exposure to HgCl2 triggers biochemical changes and modulates the expression of several proteins, resulting in damage to the myelin sheath and reduced neuronal density in the spinal cord.


Assuntos
Poluentes Ambientais/toxicidade , Cloreto de Mercúrio/toxicidade , Neurônios Motores/efeitos dos fármacos , Doenças Neurodegenerativas/induzido quimicamente , Proteoma/metabolismo , Medula Espinal/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Axônios/efeitos dos fármacos , Axônios/ultraestrutura , Masculino , Neurônios Motores/metabolismo , Neurônios Motores/ultraestrutura , Bainha de Mielina/ultraestrutura , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Proteômica , Ratos , Ratos Wistar , Medula Espinal/metabolismo , Medula Espinal/ultraestrutura
2.
Food Chem Toxicol ; 135: 110939, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31697969

RESUMO

The effects of foliar Se biofortification (Se+) of the lettuce on the transfer and toxicity of Hg from soil contaminated with HgCl2 (H) and soil collected near the former Hg smelter in Idrija (I), to terrestrial food chain are explored, with Spanish slug as a primary consumer. Foliar application of Se significantly increased Se content in the lettuce, with no detected toxic effects. Mercury exerted toxic effects on plants, decreasing plant biomass, photochemical efficiency of the photosystem II (Fv/Fm) and the total chlorophyll content. Selenium biofortification (Se+ test group) had no effect on Hg bioaccumulation in plants. In slugs, different responses were observed in H and I groups; the I/Se+ subgroup was the most strongly affected by Hg toxicity, exhibiting lower biomass, feeding and growth rate and a higher hepatopancreas/ muscle Hg translocation, pointing to a higher Hg mobility in comparison to H group. Selenium increased Hg bioavailability for slugs, but with opposite physiological responses: alleviating stress in H/Se+ and inducing it in I/Se+ group, indicating different mechanisms of Hg-Se interactions in the food chain under HgCl2 and Idrija soil exposures that can be mainly attributed to different Hg speciation and ligand environment in the soil.


Assuntos
Biofortificação/métodos , Cadeia Alimentar , Gastrópodes/metabolismo , Alface/metabolismo , Mercúrio/toxicidade , Selênio/farmacologia , Animais , 32418 , Disponibilidade Biológica , Poluentes Ambientais/farmacocinética , Poluentes Ambientais/toxicidade , Cloreto de Mercúrio/farmacocinética , Cloreto de Mercúrio/toxicidade , Mercúrio/farmacocinética , Solo/química
3.
Ecotoxicol Environ Saf ; 188: 109920, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31733937

RESUMO

This study aimed to investigate the influences of mercuric chloride (HgCl2, 250 ppm, drink water) on the growth performance, cecal morphology and microbiota of chickens (n = 60) after 30, 60, and 90 days of exposure. A control group of sixty chickens received water free of HgCl2. Our results suggested that mercury exposure reduced the body weight and changed the cecal morphology of chickens after the 90-day treatment. Furthermore, sequence analysis of 16 S rRNA gene revealed that the diversity and composition of cecal microbiota in chickens differed between the control and exposure group. At the phylum level, Proteobacteria and Tenericutes phyla both significantly increased in mercury exposure groups on day 30 while only Tenericutes phyla significantly increased on day 60. At the genus level, we observed that the change in microbial populations are most dramatic on day 30. Besides, compared with the control group, the genus Prevotellaceae_UCG-001 significantly increased in exposure group on day 30 but showed no significant difference on day 60, whereas there was a significant decrease on day 90. PICRUSt analysis revealed potential metabolic changes, such as Bacterial invasion of epithelial cells and Metabolism of xenobiotics, associated with mercury exposure in chickens. Taken together, the data show that subchronic exposure to mercury not only affected the growth and development but also caused the dysbiosis of gut microbiota, which may further induced metabolic disorders in chickens.


Assuntos
Ceco/efeitos dos fármacos , Galinhas , Poluentes Ambientais/toxicidade , Microbioma Gastrointestinal , Cloreto de Mercúrio/toxicidade , Microbiota , Animais , Bacteroidetes/isolamento & purificação , Ceco/microbiologia , Ceco/patologia , Galinhas/microbiologia , Relação Dose-Resposta a Droga , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Masculino , Microbiota/genética , Proteobactérias/isolamento & purificação , RNA Ribossômico 16S/genética
4.
Environ Health Prev Med ; 24(1): 62, 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31759394

RESUMO

BACKGROUND: Mercury has been documented as an industrial risk that posed a serious danger to human health. Mercury exposure results in oxidative stress that may lead to the pathogenesis of male reproductive dysfunction. The present study investigated the ameliorating potential of Chenopodium album L. and vitamin C against mercuric chloride-induced oxidative deterioration of reproductive functions in adult male rats. METHODS: Group 1 (control) received saline. Group 2 received Mercury (0.15 mg/kg b.w, i.p) dissolved in distilled water. Groups 3 and 4 were given oral gavage of vitamin C (200 mg/kg b.w) and the ethanolic extract of C. album (200 mg/kg b.w) respectively, along with Mercury (0.15 mg/kg b.w, i.p). Group 5 was treated only with C. album (200 mg/kg b.w). After 30 days of the treatment, the rats were dissected and their testicular tissue and the cauda epididymis were used for biochemical analysis while blood plasma was used for protein determination. RESULTS: The applied dose-treatment of Mercury-induced oxidative stress in the testis and cauda epididymis tissues of the rats was apparent by a noteworthy decrease in total protein, CAT, SOD, POD, and GST values while there was increase in ROS and TBARS levels. Furthermore, Mercury decreases daily sperm production and enhanced sperm DNA damage as noticeable by an increase in the head and tail length of comets and decrease in intact DNA. There was no significant effect on the body weight and the weight of the reproductive tissues. Treatment with C. album significantly ameliorated the total protein, ROS, and TBARS content. Similarly, the level of CAT, SOD, POD, and GST was significantly improved and the daily sperm production was significantly increased. Furthermore, C. album administration significantly protected Mercury-induced sperm DNA damage. The results of the extract treatment group were compared with those of vitamin C in detoxifying the oxidative stress and restoring the sperm parameters. CONCLUSION: C. album showed protection against Mercury-induced oxidative stress by ameliorating antioxidant enzyme activity, daily sperm production, and DNA damage in rat testes. This suggests that C. album could be beneficial against toxicity induced by an environmental toxicant.


Assuntos
Ácido Ascórbico/uso terapêutico , Chenopodium album/química , Cloreto de Mercúrio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Testículo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Ácido Ascórbico/administração & dosagem , Dano ao DNA/efeitos dos fármacos , Quimioterapia Combinada , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Espermatogênese/efeitos dos fármacos , Testículo/metabolismo , Testículo/fisiologia , Resultado do Tratamento
5.
J Trace Elem Med Biol ; 56: 60-68, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31442956

RESUMO

OBJECTIVE: Mercury is a global environmental pollutant and is responsible for several organ pathophysiology including oxidative stress-induced liver disorders. Therefore, the present study was conducted to evaluate the potential ameliorative effects of rutin on mercury chloride (HgCl2)-induced hepatotoxicity in adult male rats. METHODS: HgCl2 was intraperitoneally injected at a dose of 1.23 mg/kg body weight for 7 days alone or in combination with the orally rutin (50 and 100 mg/kg body weight). RESULTS: Rutin treatment significantly improved liver function tests [alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], and increased activities of antioxidant defense system [catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)] and glutathione (GSH) content. The histological alterations and epidermal growth factor receptor (EGFR) expression in the HgCl2-induced liver tissues were decreased by administration of rutin. Furthermore, rutin reversed the changes in levels of apoptosis and inflammation related proteins involving p53, Bcl-2 associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), cytochrome c, nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), B-cell lymphoma-3(Bcl-3) and interleukin-1ß (IL-1ß), and inhibited p38α mitogen-activated protein kinase (MAPK) and cysteine aspartate specific protease-3 (caspase-3) activations. CONCLUSION: The data of the present study suggest that rutin effectively suppress HgCl2-induced hepatotoxicity by ameliorating oxidative stress, inflammation and apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Inflamação/patologia , Fígado/patologia , Cloreto de Mercúrio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Rutina/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/metabolismo , Biomarcadores/sangue , Receptores ErbB/metabolismo , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/lesões , Masculino , Ratos Sprague-Dawley , Rutina/química , Rutina/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
6.
Chemosphere ; 234: 579-588, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31229719

RESUMO

Mercury (Hg), a significant toxic metal for nephrotoxicity, can be found in food (vegetable and seafood) and drinking water by contamination. Oxidative stress is involved in inorganic Hg-induced nephrotoxicity, but the Sirtuin1 (Sirt1)/Nrf2/OH-1 pathway and sodium (Na)/calcium (Ca) ions actions in mercuric chloride (HgCl2)-induced nephrotoxicity remains unclear to date. In this study, Kunming mice were treated HgCl2 (5 mg/kg) for 24 h to evaluate potential mechanism. Here, along with Sirt1 activation, pale kidney, hisologic conditions, typical apoptotic changes and TUNEL positive nuclei were observed under acute HgCl2 exposure. Specifically, although HgCl2 increased the expression of Nrf2, Keap1, OH-1 and NQO1, the mRNA levels of GSS, GCLC and GCLM showed no significant alterations in mice kidney. Moreover, mice exposed to HgCl2 decreased the concentrations of Mg, K, P, Mn, Fe, Zn, and elevated Na, Ca, Cu and Se in kidney. It was also observed that HgCl2 suppressed the ATPases (Na+-K+-ATPase, Ca2+-ATPase, Mg2+-ATPase and Ca2+-Mg2+-ATPase) activities and decreased the mRNA levels of Atp1a1, Atp1a2 in the kidney. Further study showed that HgCl2 elevated Na+ concentrations by markedly increased the mRNA levels of Na+ transporter. The present study revealed that HgCl2 induced Sirt1/Nrf2/OH-1 pathway activation while did not inhibit apoptosis in kidney of mice. Additionally, HgCl2 regulates Na+ concentrations, which might create secondary disorders in absorption and excretion of other ions. Altogether we assume that Sirt1/Nrf2/Na+/Ca2+ pathway might be a potential therapeutic target for treating acute HgCl2 induced nephrotoxicity.


Assuntos
Nefropatias/induzido quimicamente , Cloreto de Mercúrio/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Sirtuína 1/metabolismo , Sódio/metabolismo , Adenosina Trifosfatases/metabolismo , Animais , Cálcio/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch , Rim/metabolismo , Nefropatias/etiologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos
7.
Chemosphere ; 234: 822-829, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31247492

RESUMO

Mercury is one of the 10 toxic chemicals with major public health concerns. Continuous exposure to low levels of heavy metals including mercury is related to renal injury, especially in children. This study investigated the possible molecular mechanism of inorganic mercury-induced kidney injury. Twenty eight Kunming mice were divided into four groups (n = 7), and treated with 0, 20, 40, 80 mg/L mercuric chloride (HgCl2) in drinking water for 16 weeks respectively. All the HgCl2 exposure mice displayed different degrees of renal injury, which was diagnosed by hematoxylin and eosin stain, biochemical analysis, and ultrastructure examination. The treatment of HgCl2 inhibited the silent information regulator two ortholog 1 (Sirt1)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) signaling pathway and resulted the disorder of mitochondrial dynamics, as evidenced by the increasing expression of dynamin-related protein 1 and decreasing expression of mitofusin 2. Meanwhile, HgCl2 inhibited the nuclear factor erythroid 2-related factor 2 (Nrf2) axis. The abnormality of mitochondrial dynamics and the suppression of Nrf2 axis exacerbated oxidative stress, and then induced cell apoptosis. These findings demonstrated that the disorder of mitochondrial dynamics induced by HgCl2 activated oxidative stress, and further resulted in renal apoptosis through inhibiting the Sirt1/PGC-1α signaling pathway and the Nrf2 axis.


Assuntos
Apoptose , Rim/lesões , Cloreto de Mercúrio/toxicidade , Dinâmica Mitocondrial/efeitos dos fármacos , Estresse Oxidativo , Animais , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Dinaminas/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo
8.
J Trace Elem Med Biol ; 54: 69-78, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31109623

RESUMO

OBJECTIVE: Mercury is a dangerous industrial and environmental pollutant which induces severe damage in diverse organs in animal and humans. The aim of this study was to investigate the protective effect of rutin (50 and 100 mg/kg body weight) against mercuric chloride (HgCl2) (1.23 mg/kg b.w.) toxicity in rats. METHODS: The experiment was carried out in male Sprague Dawley rats (n = 35) which was divided into five groups as follow: control, rutin-100, HgCl2, HgCl2 + rutin-50 and HgCl2 + rutin-100. RESULTS: The results showed that HgCl2 caused a marked increase in the malondialdehyde (MDA) level and significantly decreased antioxidant enzyme activities (p < 0.05). HgCl2 also provoked inflammatory responses by elevating the levels of tumor necrosis factor-α (TNF-α), B-cell lymphoma-3 (Bcl-3), interleukin-1ß (IL-1ß), nuclear factor kappa B (NF-κB), interleukin-33 (IL-33), and activities of mitogen-activated protein kinase 14 (MAPK 14) and myeloperoxidase (MPO) (p < 0.05). HgCl2 also prompted the apoptotic pathway by increasing the levels of Bcl-2 associated X protein (Bax) and p53, expression of terminal deoxynucleotidyl transferase dUNT nick end labeling (TUNEL) and cysteine aspartate specific protease-3 (caspase-3). HgCl2 changed histological integrity of kidney and expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG) while caused a decrease in aquaporin 1 (AQP1) water channel protein level. In contrast to this, rutin significantly decreased oxidative stress, apoptosis, inflammation and histopathological alterations while increased AQP1 levels in kidney tissues (p < 0.05). CONCLUSION: The present study indicated that rutin has a nephroprotective effect due to its anti-inflammatory, antioxidant and antiapoptotic properties.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Aquaporina 1/metabolismo , Inflamação/metabolismo , Rim/efeitos dos fármacos , Cloreto de Mercúrio/toxicidade , Rutina/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
9.
Biochim Biophys Acta Biomembr ; 1861(6): 1162-1171, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30890469

RESUMO

Exposure to mercury is associated with numerous health problems, affecting different parts of the human body, including the nervous and cardiovascular systems in adults and children; however, the underlying mechanisms are yet to be fully elucidated. We investigated the role of membrane sulfatide on mercuric ion (Hg2+) mediated red blood cell (RBC) adhesion to a sub-endothelial matrix protein, laminin, using a microfluidic system that mimics microphysiological flow conditions. We exposed whole blood to mercury (HgCl2), at a range of concentrations to mimic acute (high dose) and chronic (low dose) exposure, and examined RBC adhesion to immobilized laminin in microchannels at physiological flow conditions. Exposure of RBCs to both acute and chronic levels of Hg2+ resulted in elevated adhesive interactions between RBCs and laminin depending on the concentration of HgCl2 and exposure duration. BCAM-Lu chimer significantly inhibited the adhesion of RBCs that had been treated with 50 µM of HgCl2 solution for 1 h at 37 °C, while it did not prevent the adhesion of 3 h and 24 h Hg2+-treated RBCs. Sulfatide significantly inhibited the adhesion of RBC that had been treated with 50 µM of HgCl2 solution for 1 h at 37 °C and 0.5 µM of HgCl2 solution for 24 h at room temperature (RT). We demonstrated that RBC BCAM-Lu and RBC sulfatides bind to immobilized laminin, following exposure of RBCs to mercuric ions. The results of this study are significant considering the potential associations between sulfatides, red blood cells, mercury exposure, and cardiovascular diseases.


Assuntos
Adesão Celular/efeitos dos fármacos , Eritrócitos Anormais/metabolismo , Cloreto de Mercúrio/toxicidade , Relação Dose-Resposta a Droga , Eritrócitos Anormais/citologia , Humanos , Laminina/metabolismo , Cloreto de Mercúrio/administração & dosagem
10.
Environ Sci Pollut Res Int ; 26(14): 14087-14096, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30852747

RESUMO

The liver is one of the vital and sensitive organs which are usually exposed against the toxicity of mercury (Hg) and cadmium (Cd). The main objective of the current study was to evaluate the potential toxicological effects of both Cd and Hg as individual and combined. Hepatotoxicity was evaluated by monitoring the biochemical parameters of the liver and their accumulation in the liver as well as therapeutic role of vitamin C in said toxicity in rabbits (Oryctolagus cuniculus). In this research, cadmium chloride (1.5 mg/kg), mercuric chloride (1.2 mg/kg), and vitamin C (150 mg/kg of body weight) were orally administered to treatment groups of the rabbits for 28 alternative days. Various biochemical parameters of the liver such as lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT), bilirubin, alanine aminotransferase (ALAT), total protein, and gamma glutamyl transferase (GGT) were estimated using blood samples. Some biochemical parameters like ASAT, ALAT, LDH, GGT, and bilirubin were significantly elevated (P ≤ 0.001) in individual Cd and Hg treatment groups, while the level of total protein was found to be significantly declined. The effects of Cd and Hg in the presence of vitamin C on these biochemical parameters were low as compared to metals-treated groups. Similar results were found when rabbits were treated with co-administration of both metals and vitamin C. Accumulation of Cd and Hg found to be higher in the liver. However, chemoprevention and chemotreatment with vitamin C significantly (P ≤ 0.01) minimized the toxicological effects of both metals but not regained the accumulation similar to that of the control group. The findings of this study provide awareness on accumulation of metals in the liver in rabbits and their toxicity tested through biochemical parameters as well as the therapeutic role of vitamin C in such alterations.


Assuntos
Ácido Ascórbico/farmacologia , Cádmio/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Mercúrio/toxicidade , Substâncias Protetoras/farmacologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Cloreto de Cádmio/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Feminino , L-Lactato Desidrogenase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Cloreto de Mercúrio/toxicidade , Coelhos , gama-Glutamiltransferase/metabolismo
11.
J Trace Elem Med Biol ; 52: 143-150, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30732875

RESUMO

Chronic exposure to mercury chloride (HgCl2) has been shown to promote oxidative stress and cell death in the central nervous system of adult rats displaying motor and cognitive impairments. However, there are no investigations about neurochemical function after this type of exposure in rodents that may be associated with those behavioral changes already reported. Thus, the aim of this study was to analyze glutamatergic and GABAergic dysfunctions in the motor cortex and hippocampus of adult rats, in a model of chronic exposure to HgCl2 in. Twenty rats were exposed to a daily dose of 0.375 mg/kg for 45 days. After this period, they were submitted to motor and cognitive functions tests and euthanized to collect the motor cortex and hippocampus for measurement of mercury (Hg) levels in the parenchyma and neurochemical assays for analysis of glutamatergic and GABAergic functions. It was observed that chronic exposure to HgCl2 promoted increase in total Hg levels in these two brain areas, with changes in glutamatergic transport, but without changes in GABAergic transport. Functionally this model of exposure caused the decrease of the spontaneous motor locomotion and in the process of learning and memory. In this way, our results provide evidences that glutamatergic neurochemical dysfunction can be pointed out as a strong causal factor of motor and cognitive deficits observed in rats exposed to this HgCl2.


Assuntos
Comportamento Animal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Cloreto de Mercúrio/toxicidade , Córtex Motor/efeitos dos fármacos , Administração Oral , Animais , Hipocampo/metabolismo , Masculino , Cloreto de Mercúrio/administração & dosagem , Córtex Motor/metabolismo , Ratos , Ratos Wistar
12.
Toxicol Lett ; 304: 13-20, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30630035

RESUMO

Mercury is a toxic metal that is found ubiquitously in the environment. Humans are exposed to different forms of mercury via ingestion, inhalation, and/or dermal absorption. Following exposure, mercuric ions may gain access to target cells and subsequently lead to cellular intoxication. The mechanisms by which mercury accumulation leads to cellular injury and death are not understood fully. Therefore, purpose of this study was to identify the specific intracellular mechanisms that are altered by exposure to inorganic mercury (Hg2+). Normal rat kidney (NRK) cells were exposed to a physiologically relevant form of Hg2+, as a conjugate of cysteine (10 µM or 50 µM). Alterations in oxidative stress were estimated by measuring lipid peroxidation and mitochondrial oxidative stress. Alterations in actin and tubulin were measured using specific fluorescent dyes. Calcium levels were measured using Fluo-3 AM Calcium Indicator while autophagy was identified with Premo™ Autophagy Sensor LC3B-GFP. The current findings show that exposure to Hg2+ leads to enhanced oxidative stress, alterations in cytoskeletal structure, increases in intracellular calcium, and enhanced autophagy. We have established a more complete understanding of intoxication and cellular injury induced by a relevant form of Hg2+ in proximal tubule cells.


Assuntos
Cisteína/toxicidade , Túbulos Renais Proximais/efeitos dos fármacos , Cloreto de Mercúrio/toxicidade , Citoesqueleto de Actina/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/patologia , Actinas/metabolismo , Animais , Autofagia/efeitos dos fármacos , Cálcio/metabolismo , Linhagem Celular , Cisteína/análogos & derivados , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Tubulina (Proteína)/metabolismo
13.
Environ Sci Pollut Res Int ; 26(6): 5645-5657, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30612358

RESUMO

Mercury is among the most toxic heavy metals and a widespread environmental pollutant. Mercury chloride (HgCl2) is an inorganic compound of mercury which is easily absorbed in the gastrointestinal tract and then enters the blood where it can interact with erythrocytes. In this study, the effect of HgCl2 on human erythrocytes was studied under in vitro conditions. Erythrocytes were treated with different concentrations of HgCl2 (1-100 µM) for 1 h at 37 °C. Cell lysates were prepared and assayed for several biochemical parameters. HgCl2 treatment resulted in oxidation of ferrous iron of hemoglobin to ferric form giving methemoglobin which is inactive as an oxygen transporter. However, the activity of methemoglobin reductase was increased. Hemoglobin oxidation was accompanied by heme degradation and the release of free iron. Protein oxidation was greatly increased with a simultaneous decrease in free amino and sulfhydryl groups and glutathione content. The antioxidant power of HgCl2-treated erythrocytes was impaired resulting in lowered metal reducing and free radical quenching ability of these cells. This suggests that HgCl2 induces oxidative stress in human erythrocytes. This was confirmed when superoxide anion, hydrogen peroxide, peroxynitrite, and nitric oxide generation were found to be dose-dependently increased in HgCl2-treated erythrocytes. Glycolysis and pentose phosphate pathway, the two major pathways of glucose metabolism in erythrocytes, were also inhibited. HgCl2 treatment also inhibited the plasma membrane redox system while the activities of AMP deaminase and glyoxalase-I were increased. These results show that HgCl2 induces oxidative and nitrosative stress, oxidizes hemoglobin, impairs the antioxidant defense mechanism, and alters metabolic pathways in human erythrocytes.


Assuntos
Antioxidantes/metabolismo , Substâncias Perigosas/toxicidade , Cloreto de Mercúrio/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Membrana Celular/metabolismo , Eritrócitos/efeitos dos fármacos , Eritrócitos/fisiologia , Glutationa/metabolismo , Hemoglobinas , Humanos , Peróxido de Hidrogênio , Mercúrio , Metemoglobina , Óxido Nítrico , Oxirredução , Estresse Oxidativo , Testes de Toxicidade
14.
Basic Clin Pharmacol Toxicol ; 124(2): 190-198, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30125472

RESUMO

Mercury intoxication is a public health risk factor due to its hazardous effect to several organs, including the cardiovascular system. There is evidence of endothelial dysfunction after exposure to mercury, but the effects on endothelium-dependent vasodilatation are still unknown. In the present study, we aimed to evaluate the chronic effects of high HgCl2 doses on the mechanisms of vasodilatation. Wistar rats were injected with HgCl2 (1st dose 10.86 µg/kg, and daily doses 0.014 µg/kg for 30 days i.m.), and saline was used as control. Mercury exposure reduced the acetylcholine-induced vasodilatation in aortic rings, which was restored by incubation with antioxidant tiron. Inhibition of the NO synthase, Na+ /K+ -ATPase and K+ channels indicates reduced participation of these factors. In the mercury group, there were an increased local anion superoxide and a reduced NO. The vasodilatation to exogenous NO was partially inhibited by co-incubation with TEA plus tiron, suggesting that reduced NO bioavailability is the responsible to that decreased the participation of K+ channels. Moreover, there was an increased participation of the Na+ /K+ -ATPase associated with an up-regulation of its alpha-1 subunit. In conclusion, reduced NO bioavailability plays a major role in the impaired participation of K+ channels and Na+ /K+ -ATPase in the acetylcholine-mediated relaxation, although sodium pump is up-regulated probably as a compensatory mechanism.


Assuntos
Cloreto de Mercúrio/toxicidade , Óxido Nítrico/deficiência , Canais de Potássio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Vasodilatação/efeitos dos fármacos , Acetilcolina/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Disponibilidade Biológica , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Hemodinâmica , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Prostaglandina-Endoperóxido Sintases/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Sistema Renina-Angiotensina
15.
Biol Trace Elem Res ; 191(1): 177-182, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30523573

RESUMO

The aim of this study was to investigate the effects of mercury chloride and boric acid on rat (Wistar albino) erythrocyte: glucose 6-phosphate dehydrogenase (G6PD), 6-phosphoglucona-te dehydrogenase (6PGD), thioredoxin reductase (TrxR), glutathione reductase (GR) and glutathione S-transferase (GST) enzymes in vivo, and the rat erythrocyte G6PD enzyme in vitro. In the in vivo study, 24 male rats were divated into three different groups: control (C), mercury chloride (M), and mercury chloride + boric acid (M + BA). At the completion of this study, a significant degree of inhibition for both G6PD and GST enzyme activity was observed in the M groups when compared to the C group (p < 0.05), and no significant effect was observed in the 6PGD enzyme. However, there was significantly increased TrxR and GR enzyme activity of both the M and M + BA groups (p < 0.05). In the in vitro study, the G6PD enzyme from rat erythrocytes was purified with 2',5'-ADP Sepharose-4B affinity chromatography, and the effect of both mercury chloride and boric acid on the enzyme activity was investigated. The results showed that boric acid increased the G6PD enzyme activity while the mercury ions that inhibited the enzyme activity (IC50 values of 346 µM and Ki values of 387 µM) were noncompetitive.


Assuntos
Ácidos Bóricos/toxicidade , Eritrócitos/enzimologia , Cloreto de Mercúrio/toxicidade , Oxirredutases/metabolismo , Animais , Masculino , Ratos
16.
Ecotoxicol Environ Saf ; 169: 516-522, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30472476

RESUMO

Mercury is one of the most harmful pollutant that threat marine biota. This study assessed the Hg impact on the fatty acid (FA) composition and the antioxidant statues in Holothuria forskali body wall tissue. Specimens were exposed to HgCl2 graded doses (40, 80 and 160 µg L-1) for 96 h. A decrease in linoleic, arachidonic and eicosapentaenoic acid levels and an increase of docosahexaenoic acid were mainly observed at the nominal tested dose. The exposure to the upper dose promoted oxidative stress with an increase of malondialdehyde, hydrogen peroxide, advanced oxidation protein product, glutathione and non-protein thiols levels. Moreover, a decrease in catalase and an increase in superoxide dismutase and glutathione peroxidase activities were observed. Yet, an increase of the metallothionein level was registered in all treated groups. This study confirmed the Hg toxicity on the redox statue of H. forskali and highlighted the usefulness of the FA composition as an early sensitive bioindicators.


Assuntos
Antioxidantes/metabolismo , Ácidos Graxos/metabolismo , Holothuria/efeitos dos fármacos , Cloreto de Mercúrio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores/metabolismo , Holothuria/metabolismo , Mar Mediterrâneo , Cloreto de Mercúrio/análise , Oxirredução , Água do Mar/química , Tunísia , Poluentes Químicos da Água/análise
17.
Environ Sci Pollut Res Int ; 26(4): 3909-3920, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30547340

RESUMO

Cadmium and mercury are among the most toxic and dangerous environmental pollutants that may cause fatal implications. Vitamin C is an important chain-breaking antioxidant and enzyme co-factor against heavy metals. The objective of the present study was to evaluate the toxicological effects of cadmium chloride, mercuric chloride, and their co-administration on biochemical parameters of blood serum and metal bioaccumulation in kidneys and also to elucidate the protective effect of vitamin C in rabbits against these metals. In the current research, cadmium chloride (1.5 mg/kg), mercuric chloride(1.2 mg/kg), and vitamin C (150 mg/kg of body weight) were orally administered to eight treatment groups of the rabbits (1, control; 2, vitamin; 3, CdCl2; 4, HgCl2; 5, vitamin + CdCl2; 6, vitamin + HgCl2; 7, CdCl2 + HgCl2, and 8, vitamin + CdCl2 + HgCl2). After the biometric measurements of all experimental rabbits, biochemical parameters viz. creatinine, cystatin C, uric acid, and alkaline phosphatase (ALP) and metal bioaccumulation were determined using commercially available kits and atomic absorption spectrophotometer, respectively. The levels of creatinine (28.3 ± 1.1 µmol/l), cystatin C (1932.5 ± 38.5 ηg/ml), uric acid (4.8 ± 0.1 mg/day), and ALP (51.6 ± 1.1 IU/l) were significantly (P < 0.05) increased due to administration of mercuric chloride but in the presence of vitamin C, the effects of mercuric chloride on creatinine (21.9 ± 1.4 µmol/l), cystatin C (1676.2 ± 42.2 ηg/ml), uric acid (3.9 ± 0.1 mg/day), and ALP (43.3 ± 0.8 IU/l) were less as compared to metal-exposed specimens. Similar results were found in rabbits treated with cadmium chloride and vitamin C and also with co-administration of both metals and vitamin C. Because of the bio-accumulative nature of cadmium chloride and mercuric chloride, these metals were accumulated in kidneys of rabbits, which might lead to deleterious effects. The results of the present study provide an insight into the toxicity of the cadmium chloride, mercuric chloride, and/or their combination on biochemical parameters as well as kidneys of the rabbits and the ameliorating potential of vitamin C against these metals is also evaluated.


Assuntos
Ácido Ascórbico/farmacologia , Cloreto de Cádmio/toxicidade , Rim/efeitos dos fármacos , Cloreto de Mercúrio/toxicidade , Administração Oral , Fosfatase Alcalina/sangue , Animais , Antioxidantes/farmacologia , Cádmio/farmacocinética , Cádmio/toxicidade , Cloreto de Cádmio/administração & dosagem , Creatinina/sangue , Cistatina C/sangue , Poluentes Ambientais/farmacocinética , Poluentes Ambientais/toxicidade , Rim/metabolismo , Cloreto de Mercúrio/administração & dosagem , Mercúrio/farmacocinética , Mercúrio/toxicidade , Substâncias Protetoras/farmacologia , Coelhos , Ácido Úrico/sangue
18.
J Diet Suppl ; 16(1): 51-65, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29451842

RESUMO

This research was intended to investigate the protective effect of leaf ethanolic extract Etlingera hemisphaerica Blume (LE3H) against mercuric chloride (HgCl2) toxicity in blood of mice (Mus musculus). The experimental animals, 95 male M. musculus, received drink and food ad libitum. Three materials were tested: LE3H (0.13, 0.26, 0.39 mg/g body weight [bw]) was administered by gavage; HgCl2 (5 mg/kg bw) was administrated by gavage or intraperitoneal injection; and Imunos (the nutritional supplement to stimulate the immune system; 0.2 mg/g bw), as a positive control for LE3H treatment, was given by gavage. Blood samples were taken from the tails for determining number of blood cells. The animals were killed by cervical dislocation (CD), and then blood samples were collected from the hearts for protein electrophoresis. Results revealed the same number of leukocytes with LE3H (0.39 mg/g bw) treatment as with the Imunos treatment. HgCl2 administration increased leukocytes and decreased erythrocytes; HgCl2 administration followed by LE3H (0.39 mg/g bw) treatment protected the amount of blood cells as well as the control. HgCl2 administration showed a new 125 kDa protein and caused overexpression of 48 kDa protein; this protein profile could be protected by LE3H (0.39 mg/g bw) treatment as in the control condition. We conclude that LE3H provides a protective effect against HgCl2 toxicity in blood of M. musculus.


Assuntos
Cloreto de Mercúrio/toxicidade , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Zingiberaceae , Animais , Proteínas Sanguíneas/metabolismo , Eritrócitos/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Masculino , Cloreto de Mercúrio/sangue , Intoxicação por Mercúrio/sangue , Intoxicação por Mercúrio/prevenção & controle , Camundongos , Folhas de Planta
19.
Ecotoxicol Environ Saf ; 170: 461-467, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30553924

RESUMO

The objective of this work was to evaluate the antioxidant, metal chelating and cytoprotective activity of the Eugenia jambolana Lam. extract, as well as of its flavonoid and tannic fractions, against the action of Mercury Chloride (HgCl2). Flavonoids were quantified and an LC-MS chromatographic analysis was performed to identify secondary metabolites. Fe2+ and Fe3+ chelation tests and antioxidant activity were carried out using the FRAP method. Microbiological tests were performed by microdilution to determine the Minimum Inhibitory Concentration (MIC). From these results the Minimum Bactericidal (MBC) and Minimum Fungicide Concentration (MFC) were evaluated. The allelopathy and cytoprotection assays were performed using eukaryotic and prokaryotic models. The results revealed the presence of phenolic acids and flavonoids in the E. jambolana extract and fractions. The sub-allelopathic concentration (64 µg/mL) was used and the results demonstrated the E. jambolana potential cytoprotective effect against mercury chloride.


Assuntos
Produtos Biológicos/química , Cloreto de Mercúrio/toxicidade , Syzygium/química , Alelopatia , Anti-Infecciosos/química , Antioxidantes/química , Citoproteção , Flavonoides/química , Alface/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Extratos Vegetais/química
20.
Cell Mol Biol (Noisy-le-grand) ; 64(13): 84-88, 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30403601

RESUMO

In this study, the effect of boric acid on the important trace elements copper (Cu), iron (Fe), zinc (Zn), manganese (Mn) and nickel (Ni) in liver and kidney tissue of rats treated with mercury chloride was investigated. Twenty-four male Wistar albino rats (weighing 200 ± 300 g) were divided into 3 groups: Control (C), Mercury chloride (HgCl2), Mercury chloride (HgCl2) + boric acid (BA). Iron and copper were decreased whereas Mn, Zn and Ni levels were increased in liver tissue in Hg administered group compared to control. Cu (p<0.01) and Mn (p<0.001) levels were increased in Hg + BA administered group compared to Hg group. Renal tissue Cu (p<0.01), Mn and Zn levels were increased whereas Ni (p<0.05) and Fe levels were decreased in Hg administered group compared to control group. Cu (p<0.001) and Zn (p<0.05) content increased in Hg + BA group compared to control group. As a result, it is thought that boric acid may have an effect on important trace element levels such as copper (Cu), iron (Fe), zinc (Zn), manganese (Mn), nickel (Ni) in case of oxidative stress caused by mercury chloride.


Assuntos
Ácidos Bóricos/farmacologia , Elementos , Rim/metabolismo , Fígado/metabolismo , Cloreto de Mercúrio/toxicidade , Animais , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Ratos Wistar
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