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1.
Environ Sci Pollut Res Int ; 28(14): 17482-17494, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33394435

RESUMO

Heavy metal contamination including mercury (Hg) has become one of the most serious environmental problems facing humans and other living organisms. Here, the hepatoprotective effects of Z. spina-christi leaf extract (ZCE) against inorganic mercury salt (mercuric chloride; HgCl2)-induced hepatotoxicity model was investigated in rats. Mercury concentration, liver function markers, oxidative stress markers, inflammation, cell death indicators, and histopathology were assessed. ZCE protected against HgCl2-induced hepatotoxicity, decreased Hg concentration, lipid peroxidation, and nitric oxide, increased glutathione, superoxide dismutase, catalase, and glutathione recycling enzymes (peroxidase and reductase), and upregulated nuclear factor-erythroid 2-related factor 2 (Nrf2) gene expression in HgCl2-intoxicated rat hepatic tissue. Nrf2 downstream gene and heme oxygenase-1 were also upregulated, confirming that hepatoprotection by ZCE against HgCl2-induced liver damage involved activation of the Nrf2/antioxidant response element pathway. ZCE also decreased the expression and production of pro-inflammatory cytokines and pro-apoptotic proteins and increased anti-apoptotic protein Bcl-2. Immunohistochemical analysis of liver tissues of HgCl2-treated rats confirmed the alternations of apoptotic-related protein expression. Our data demonstrated that post-administration of ZCE attenuated HgCl2-induced liver damage by activating the Nrf2/HO-1 signaling pathway. Therefore, administering this extract may be a novel therapeutic strategy for inorganic mercury intoxication.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Ziziphus , Animais , Antioxidantes/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Fígado/metabolismo , Masculino , Cloreto de Mercúrio/metabolismo , Cloreto de Mercúrio/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Ratos , Ziziphus/metabolismo
2.
Toxicol Lett ; 341: 23-32, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33476711

RESUMO

Mercury is an environmental pollutant and a threat to human health. Mercuric chloride (HgCl2)-induced acute renal failure has been described by several reports, but the mechanisms of renal dysfunction remain elusive. This study tested the hypothesis that HgCl2 directly impairs renal vascular reactivity. Additionally, due to the mercury toxicity on the proximal tubule, we investigated whether the HgCl2-induced natriuresis is accompanied by inhibition of Na+/H+ exchanger isoform-3 (NHE3). We found that 90-min HgCl2 infusion (6.5 µg/kg i.v.) remarkably increased urinary output, reduced GFR and renal blood flow, and increased vascular resistance in rats. "In vitro" experiments of HgCl2 infusion in isolated renal vascular bed demonstrated an elevation of perfusion pressure in a concentration- and time-dependent manner, associated with changes on the endothelium-dependent vasodilatation and the flow-pressure relationship. Moreover, by employing "in vivo" stationary microperfusion of the proximal tubule, we found that HgCl2 inhibits NHE3 activity and increases the phosphorylation of NHE3 at serine 552 in the renal cortex, in line with the HgCl2-induced diuresis. Changes in renal proximal tubular function induced by HgCl2 were parallel to increased urinary markers of proximal tubular injury. Besides, atomic spectrometry showed that mercury accumulated in the renal cortex. We conclude that acute HgCl2 exposure causes renal vasoconstriction that is associated with reduced endothelial vasodilator agonist- and flow-mediated responses and inhibition of NHE3-mediated sodium reabsorption. Thus, our data suggest that HgCl2-induced acute renal failure may be attributable at least in part by its direct effects on renal hemodynamics and NHE3 activity.


Assuntos
Endotélio Vascular/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , Rim/irrigação sanguínea , Cloreto de Mercúrio/toxicidade , Trocador 3 de Sódio-Hidrogênio/antagonistas & inibidores , Animais , Poluentes Ambientais/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Rim/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Resistência Vascular/efeitos dos fármacos
3.
Toxicol Appl Pharmacol ; 413: 115405, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33444613

RESUMO

Cardiovascular diseases are among the main causes of mortality in the world. There is evidence of cardiovascular harm after exposure to low lead or mercury concentrations, but the effects of chronic exposure to the association of low doses of these toxic metals are still unknown. This work evaluated after 4 weeks, the association effects of low concentrations of lead and mercury on blood pressure and vascular resistance reactivity. Wistar rats were exposed for 28 days to lead acetate (1st dose of 4 µg/100 g and subsequent doses of 0.05 µg /100 g/day to cover daily losses) and mercury chloride (1st dose of 2.17 µg/kg and subsequent doses of 0.03 µg/kg/ day to cover daily losses) and the control group received saline, i.m. Results showed that treatment increased blood pressure and induced left ventricular hypertrophy. The mesenteric vascular reactivity to phenylephrine and the endothelium-dependent vasodilator response assessed by acetylcholine did not change. Additionally, reduced involvement of vasoconstrictor prostanoids derived from cyclooxygenase was observed in the PbHg group. By other regulatory routes, such as potassium channels, the vessel showed a greater participation of BKCa channels, and a reduction in the participation of Kv channels and SKCa channels. The endothelium-independent smooth muscle relaxation was significantly impaired by reducing cGMP, possibly through the hyperstimulation of Phosphodiesterase-5 (PDE5). Our results suggested that exposure to low doses of lead and mercury triggers this compensatory mechanism, in response to the augment of arterial pressure.


Assuntos
Pressão Arterial/efeitos dos fármacos , GMP Cíclico/metabolismo , Cloreto de Mercúrio/toxicidade , Músculo Liso Vascular/efeitos dos fármacos , Compostos Organometálicos/toxicidade , Vasodilatação/efeitos dos fármacos , Animais , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Regulação para Baixo , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/induzido quimicamente , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/metabolismo , Artérias Mesentéricas/fisiopatologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiopatologia , Ratos Wistar , Sistemas do Segundo Mensageiro , Fatores de Tempo , Resistência Vascular/efeitos dos fármacos
4.
Chemosphere ; 270: 129438, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33429232

RESUMO

Mercury (Hg) causes great health concerns due to its extreme neurotoxicity. However, here we show that pretreatment of sparingly soluble mercury compound (HgS) could induce adaptive mechanisms in zebrafish, which can resist the neurotoxic effects of mercury chloride (HgCl2). In this study, zebrafish were treated with HgS (in the form of 99% HgS arising from traditional Ayurvedic medicine Rasasindura (RS), chosen for its particle and crystallite sizes). This work was prompted by the traditional use of this form of HgS to treat nervous and immune-related diseases. Our investigation on zebrafish behaviour showed that RS pretreated fish group (RS-HG) was less severely affected by HgCl2 exposure, as compared to the RS non-treated (VC-HG) group. Further, biochemical tests showed that RS pretreatment prevents alteration of reactive oxygen species (ROS), acetylcholinesterase (AChE), and cortisol as compared to the VC-HG group. Proteomics and bioinformatics studies of zebrafish brain tissues suggested that Rasasindura (RS-HG group) protects alteration of various protein expression related to KEGG pathways, including citrate cycle (TCA cycle) and glutathione metabolism that are directly or indirectly linked to the oxidative stress, against HgCl2 induced neurotoxicity. We found that adaptive mechanisms were initiated by the initiation of response to stress (enrichment of GO:0006950 pathway), due to the accumulation of a small amount of ionic Hg (60 ± 10 ng/g) after 15 days of RS treatment. These adaptive mechanisms avoid further adverse neurotoxicity of HgCl2. Thus, HgS (RS) pretreatment can induce protective effects in zebrafish.


Assuntos
Mercúrio , Peixe-Zebra , Animais , Cloreto de Mercúrio/toxicidade , Compostos de Mercúrio , Proteômica , Sulfetos
5.
Toxicol Appl Pharmacol ; 412: 115379, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33358697

RESUMO

Exposure to heavy metals may have toxic effects on several human organs causing morbidity and mortality. Metals may trigger or exacerbate autoimmunity in humans. Inbred mouse strains with certain H-2 haplotypes are susceptible to xenobiotic-induced autoimmunity; and their immune response to metals such as mercury, gold, and silver have been explored. Serum antinuclear antibodies (ANA), polyclonal B-cell activation, hypergammaglobulinemia and tissue immune complex deposition are the main features of metal-induced autoimmunity in inbred mice. However, inbred mouse strains do not represent the genetic heterogeneity in humans. In this study, outbred Swiss Webster (SW) mice exposed to gold or mercury salts showed immune and autoimmune responses. Intramuscular injection of 22.5 mg/kg.bw aurothiomalate (AuTM) induced IgG ANA in SW mice starting after 5 weeks that persisted until week 15 although with a lower intensity. This was accompanied by elevated serum levels of total IgG antibodies against chromatin and total histones. Exposure to gold led to development of serum IgG autoantibodies corresponding to H1 and H2A histones, and dsDNA. Both gold and mercury induced polyclonal B-cell activation. Eight mg/L mercuric chloride (HgCl2) in drinking water, caused IgG antinucleolar antibodies (ANoA) after 5 weeks in SW mice accompanied by immune complex deposition in kidneys and spleen. Serum IgG antibodies corresponding to anti-fibrillarin, and anti-PM/Scl-100 antibodies, were observed in mercury-exposed SW mice. Gold and mercury trigger systemic autoimmune response in genetically heterogeneous outbred SW mice and suggest them as an appropriate model to study xenobiotic-induced autoimmunity.


Assuntos
Anticorpos Antinucleares/sangue , Autoimunidade/efeitos dos fármacos , Linfócitos B/efeitos dos fármacos , Tiomalato Sódico de Ouro/toxicidade , Imunoglobulina G/sangue , Ativação Linfocitária/efeitos dos fármacos , Cloreto de Mercúrio/toxicidade , Administração Oral , Animais , Complexo Antígeno-Anticorpo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Cromatina/imunologia , Proteínas Cromossômicas não Histona/imunologia , Exorribonucleases/imunologia , Complexo Multienzimático de Ribonucleases do Exossomo/imunologia , Feminino , Tiomalato Sódico de Ouro/administração & dosagem , Histonas/imunologia , Injeções Intramusculares , Rim/efeitos dos fármacos , Rim/imunologia , Cloreto de Mercúrio/administração & dosagem , Camundongos , Baço/efeitos dos fármacos , Baço/imunologia
6.
Chemosphere ; 263: 128137, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33297125

RESUMO

Mercury (Hg) is considered to be one of the most toxic and ubiquitously distributed metals in the aquatic system. Meanwhile, the temperature increase of water bodies due to global climatic changes, may affect ecosystems through alterations of the metal properties or by affecting the susceptibility of organisms. To study the physiological stress of mercury chloride on grass carp Ctenopharyngodon idella at different temperatures, we investigated the effects of water temperature and/or mercury chloride (HgCl2) on growth performance (SGR-the specific growth rate, HSI-hepato-somatic index, CF-condition factor) and the thyroid hormones levels (T3-triiodothyronine; T4-thyroxine), as well as the expression levels of related genes involved growth and hypothalamus-pituitary-thyroid (HPT) axis. Fish (45.37 ± 3.58 g) were acclimated to 15, 20, 25, 30 or 35 °C and co-exposed to 0.0 or 0.039 mg/L HgCl2 for 4 weeks in triplicates. Three-way ANOVA revealed that all variables were significantly affected by water temperature, HgCl2 exposure, exposure time and their interactions. It was found that fish reared in Hg-free group at 25 °C showed the optimum growth. Otherwise, T4 concentrations were decreased, while T3 levels remained constant following exposure to HgCl2, which was explained by the up-regulation of the dio2 gene. Our data provide evidences that increased temperatures can potentiate HgCl2 toxicity, but the exact mechanism of the effects of temperature coupled HgCl2 on fish is not full clear, which should be give more attention in future.


Assuntos
Carpas , Mercúrio , Animais , Cloretos , Ecossistema , Cloreto de Mercúrio/toxicidade , Mercúrio/toxicidade , Temperatura
7.
Eur. j. anat ; 24(5): 381-389, sept. 2020. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-195275

RESUMO

Mercuric chloride (MC) is a chemical compound made from a combination of mercury and chlorine causing intracellular oxidative stress generation. Allium jesdianum (AJ), as a member of the Liliaceae family, has various pharmacological and strong antioxidant properties. This study aimed to evaluate the probable therapeutic effects of AJ against hepatocytes degeneration, inflammation, apoptotic changes and oxidative injuries induced by MC ad-ministration. Sixty-four rats were randomly divided in eight groups (n = 8) including groups of control, MC (50 mg/kg), AJ (500, 1000, 2000 Mug/ml), and MC+AJ. They were intraperitoneally and orally administrated for one week. Nitrite oxide, lipid peroxidation (LP) levels, and Ferric Reducing Ability of Plasma (FRAP) assays were conducted to evaluate the intracellular antioxidant index


No disponible


Assuntos
Animais , Masculino , Ratos , Fígado/anatomia & histologia , Dissecação/veterinária , Allium , Fígado/efeitos dos fármacos , Cloreto de Mercúrio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Inflamação/patologia , Apoptose/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Extratos Vegetais , Variação Anatômica , Análise de Variância
8.
Chemosphere ; 260: 127611, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32758780

RESUMO

Mercury (Hg) is known as a highly toxic heavy metal, and its toxicity varies depending on its form due to different toxicokinetics between inorganic and organic Hg. Limited information on comparison of Hg toxicity concerning its chemical form by oral exposure is currently available in cultured fishes. Therefore, we conducted a comparative study to have a better understanding of distinct toxic effects between mercuric chloride (HgCl2) and methylmercury chloride (CH3HgCl) in Korean rockfish. The 12-weeks dietary exposure of HgCl2 and CH3HgCl with its graded levels (0.4-6.4 ppm) (2 × 5 factorial design) in the young-of-the-year rockfish (initial weight: 82 ± 0.3 g) resulted in neither interactive nor main effects on whole-organism responses, including growth, feed utilization, and survival. However, the distinct pattern of Hg accumulation between the two forms in dorsal muscle, brain, liver and kidney tissues was observed, showing that the rockfish fed the CH3HgCl-contained diets exhibited the dose-dependent accumulation throughout the sampling points (1, 2, 4, 8, and 12 weeks post feeding), whereas those fed the HgCl2-contained diets did not show such response. The CH3HgCl exposure induced higher oxidative stress and immunotoxicity, reflected by the elevated plasma superoxide dismutase and lysozyme activities, respectively. In addition, the CH3HgCl-induced alteration in plasma measurements, including the plasma aspartate transaminase activity and total protein level was found. Taken together, the dietary exposure of methylmercury chloride had more pronounced toxic effects than mercuric chloride in the young-of-year rockfish, needed to be taken into consideration for regulation of maximum allowed levels for Hg by its chemical form.


Assuntos
Cloreto de Mercúrio/toxicidade , Compostos de Metilmercúrio/toxicidade , Perciformes/fisiologia , Poluentes Químicos da Água/toxicidade , Animais , Encéfalo/metabolismo , Dieta , Mercúrio/metabolismo , Estresse Oxidativo , Perciformes/metabolismo , República da Coreia , Superóxido Dismutase/metabolismo
9.
Environ Sci Pollut Res Int ; 27(32): 40563-40572, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32671705

RESUMO

This study evaluated the toxic effects of inorganic mercury (Hg) in pregnant and lactating rats, as well as the possible protective effect of zinc (Zn) and N-acetylcysteine (NAC). Pregnant and lactating rats were pre-treated with ZnCl2 (27 mg/kg) and/or NAC (5 mg/kg) and after 24 h, they were exposed to HgCl2 (10 mg/kg). Animals were sacrificed 24 h after Hg exposure, and biochemical tests and metal determination were performed. Regarding pregnant rats, Hg exposure caused kidney, blood, and placenta δ-aminolevulinic acid dehydratase (δ-ALA-D) activity inhibition, and the pre-treatments showed a tendency of protection. Moreover, all the animals exposed to Hg presented high Hg levels in the kidney, liver, and placenta when compared with control group. Pregnant rats pre-exposed to Zn (Zn-Hg and Zn/NAC-Hg groups) presented an increase in hepatic metallothionein levels. Therefore, lactating rats exposed to Hg presented renal and blood δ-ALA-D inhibition; the pre-treatments showed a tendency to prevent the renal δ-ALA-D inhibition and prevented the blood δ-ALA-D inhibition caused by Hg. Lactating rats exposed to Hg presented high Hg levels in the kidney and liver. These results showed that 10 mg/kg of HgCl2 causes biochemistry alterations in pregnant and lactating rats, and Zn and NAC present promising results against these damages.


Assuntos
Acetilcisteína , Mercúrio , Acetilcisteína/farmacologia , Animais , Feminino , Rim , Lactação , Fígado , Cloreto de Mercúrio/toxicidade , Mercúrio/toxicidade , Sintase do Porfobilinogênio , Gravidez , Ratos , Zinco
10.
Ecotoxicol Environ Saf ; 201: 110801, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32502906

RESUMO

Mercury (Hg) pollution poses global human health and environmental risks. However, still knowledge gaps exist on both exposures and health effects. Here, we combined transcriptome sequencing technique to further investigate the specific mechanisms of inorganic Hg toxicity in the kidney. Strikingly, transcriptomic analysis revealed that 4174 unigenes (including 2646 upregulated and 1528 downregulated unigenes) were differentially expressed under acute HgCl2 (5 mg/kg) exposure in the kidney. Additionally, we observed that HgCl2 selectively induced tumor necrosis factor superfamily (TNFSF) to participate in renal damage, which was consistent with the high-throughput sequencing data. The phenomenon is accompanied by NLRP3 inflammasome and NF-κB signal activation in the kidney. Simultaneously, ELISA results shown that TNF-α, IL-1ß and IL-6 concentrations in the kidney were significant increased. KEGG enrichment analysis showed that peroxisome proliferators-activated receptors (PPAR) signaling pathway might be vital toxic mechanism of Hg in the kidney. Then, our data showed that PPARγ agonist (GW 1929) attenuated HgCl2 (15 µg/ml)-induced apoptosis and NLRP3 inflammasome activation via decreasing translocation of NF-κB and increasing Bcl2 levels in vitro. Along with this, we demonstrated that PPARγ antagonists (GW9662) effectively aggravated HgCl2-induced nephrotoxicity. Overall, our results suggested that PPARγ signaling pathway is considered to be a protective mechanism to combat against HgCl2-triggered NLRP3 inflammasome activation and apoptosis.


Assuntos
Poluentes Ambientais/toxicidade , Inflamassomos/metabolismo , Rim/efeitos dos fármacos , Cloreto de Mercúrio/toxicidade , NF-kappa B/metabolismo , PPAR gama/agonistas , Transcriptoma/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Benzofenonas/farmacologia , Regulação para Baixo , Humanos , Rim/metabolismo , Rim/patologia , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transporte Proteico , Transdução de Sinais , Tirosina/análogos & derivados , Tirosina/farmacologia , Regulação para Cima
11.
Andrologia ; 52(3): e13524, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32022330

RESUMO

This study investigated the effects of rutin against reproductive damage caused by toxic mercury in male rats. Thirty-five Sprague Dawley rats were used. Control group was injected with saline for 7 days. The rutin-100 group received 100 mg/kg/b.w. rutin for 7 days. Mercuric chloride (HgCl2 ) group received 1.23 mg/kg/b.w. of HgCl2 for 7 days. Mercury chloride + rutin-50 group received 50 mg/kg/b.w. rutin and HgCl2 1.23 mg/kg/b.w. for 7 days. HgCl2  + rutin-100 group received 100 mg/kg/b.w. rutin and HgCl2 1.23 mg/kg/b.w. for 7 days. It was detected that HgCl2 treatment increased malondialdehyde (MDA) levels, tumour necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) expressions, necrosis and degeneration of spermatogonium, dead and abnormal sperm percentages; tubular walls thinning; and decreased antioxidant enzyme activities and sperm motility. It was determined that rutin application reduced testicular damage caused by HgCl2 . In conclusion, rutin administration may treat HgCl2 toxicity in testes.


Assuntos
Poluentes Ambientais/toxicidade , Cloreto de Mercúrio/toxicidade , Rutina/administração & dosagem , Espermatogônias/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Masculino , Modelos Animais , Necrose/induzido quimicamente , Necrose/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Motilidade Espermática/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatogônias/patologia , Testículo/patologia
12.
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
13.
Environ Sci Pollut Res Int ; 27(3): 3401-3412, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31840221

RESUMO

Mercury (Hg) is a heavy metal toxicant, causing several adverse reactions to animals and humans including reproductive dysfunction. The potential protective role of Ziziphus spina-christi leaf extract (ZSCLE) against testicular impairments associated with mercury chloride (HgCl2) exposure in rats was investigated in the current study. Four experimental groups were employed as follows (n = 7): group I served as control, group II was gavaged with ZSCLE (300 mg/kg), group III was administered with HgCl2 (0.4 mg/kg), and group IV was preadministered with ZSCLE 1 h before HgCl2. All groups were treated daily for 28 days. The exposure to HgCl2 caused a marked increase in Hg concentration in the testicular tissue, which was accompanied with a decrease in testis index. A reproductive impairment was recorded following HgCl2 exposure as verified through the decrease in levels of testosterone, luteinizing, and follicle-stimulating hormones. HgCl2 was found to enhance the development of oxidative damage in the testicular tissue as presented by the imbalance between pro-oxidants and antioxidant molecules. In addition, excessive release of tumor necrosis factor-α and interleukin-1ß was recorded in response to HgCl2 intoxication. Furthermore, a disturbance in the apoptotic proteins in favor of the pro-apoptotic proteins was also observed following HgCl2 intoxication. However, ZSCLE administration along with HgCl2 abolished significantly the molecular, biochemical, and histopathological alterations induced by HgCl2 intoxication. Our findings suggest that ZSCLE could be used to mitigate reproductive dysfunction associated with HgCl2 exposure.


Assuntos
Substâncias Perigosas/toxicidade , Cloreto de Mercúrio/toxicidade , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Ziziphus , Animais , Antioxidantes , Masculino , Mercúrio , Estresse Oxidativo , Ratos , Testículo/efeitos dos fármacos , Testículo/fisiologia
14.
Metallomics ; 12(1): 144-153, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31793599

RESUMO

Mercury is a highly poisonous heavy metal abundantly found in the environment in its inorganic form. Although evidence have been provided about the possible role of inorganic mercury in the pathology of Alzheimer's disease (AD), its effect on cognitive and mitochondrial functions have not yet been completely understood. Thus, the purpose of the present study was to examine the effects of the chronic exposure to mercuric chloride (0.4, 0.8 and 1.6 mg kg-1 per day for 3 weeks) through drinking water (by gavage) on spatial learning and memory and hippocampal mitochondrial function in beta-amyloid treated rats (1 µg per µL per side, intrahippocampally). The acquisition and retention of spatial memory were evaluated by the Morris water maze (MWM) test. Several parameters of hippocampal mitochondrial function were also measured. The results indicated that mercury impaired spatial learning and memory as well as aggravated Aß-induced memory impairments in a concentration-dependent manner. Furthermore, mercury exposure resulted in a significant increase in ROS generation, MMP collapse, mitochondrial swelling, glutathione oxidation, lipid peroxidation, and outer membrane damage. In addition, a reduced cytochrome c oxidase (complex IV) activity and elevated ADP/ATP ratio in the rats' hippocampus was also observed. The findings of the current study revealed that chronic mercury exposure led to mitochondrial dysfunction, which resulted in spatial memory impairments. The results also showed that mercury can exacerbate the toxic effects of Aß on spatial memory and hippocampal mitochondrial function.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Cloreto de Mercúrio/toxicidade , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Memória Espacial/efeitos dos fármacos , Animais , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Ratos , Ratos Wistar
15.
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
16.
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 , Bioacumulação , Disponibilidade Biológica , Poluentes Ambientais/farmacocinética , Poluentes Ambientais/toxicidade , Cloreto de Mercúrio/farmacocinética , Cloreto de Mercúrio/toxicidade , Mercúrio/farmacocinética , Solo/química
17.
Drug Chem Toxicol ; 43(3): 287-297, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30554537

RESUMO

Mercury (Hg) is among the most deleterious contaminant in the aquatic environment and presents a serious risk to humans and ecosystems. This study evaluated the effects of Hg on oxidative stress biomarkers, DNA integrity and histological structure of the respiratory tree of Holothuria forskali exposed to different concentrations of mercury chloride HgCl2 (0.04, 0.08 and 0.16 mg L-1) for 96 h. Exposure of H. forskali to Hg led to oxidative stress with an increase in Malondialdehyde (MDA), hydrogen peroxide (H2O2), advanced oxidation protein product (AOPP) and protein carbonyls (PCO) levels in the treated groups. Alteration of the antioxidant system was also confirmed by the significant increase in glutathione (GSH), nonprotein thiol (NPSH) and vitamin C contents. Moreover, the enzymatic activity of superoxide dismutase (SOD), Glutathione peroxidase (GPX) and Catalase (CAT) increased significantly. Our research revealed that total Metallothionein (MTs) content enhanced in a dose-dependent manner. Interestingly, the exposure to this metal provoked a decrease in Acetylcholinesterase (AChE) activity. Hg genotoxicity was further evidenced by a random DNA degradation that was observed in the treated groups. The histopathological findings confirmed the biochemical results. Overall, our results indicated that mercury-induced genotoxicity, oxidative damage and histopathological injuries in the respiratory tree of H. forskali.


Assuntos
Cloreto de Mercúrio/toxicidade , Metalotioneína/genética , Mutagênicos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Relação Dose-Resposta a Droga , Holothuria/efeitos dos fármacos , Cloreto de Mercúrio/administração & dosagem , Testes de Mutagenicidade , Mutagênicos/administração & dosagem , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Sistema Respiratório/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Poluentes Químicos da Água/administração & dosagem
18.
Cardiovasc Toxicol ; 20(3): 197-210, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31338744

RESUMO

Mercury is a heavy metal associated with cardiovascular diseases. Studies have reported increased vascular reactivity without changes in systolic blood pressure (SBP) after chronic mercury chloride (HgCl2) exposure, an inorganic form of the metal, in normotensive rats. However, we do not know whether individuals in the prehypertensive phase, such as young spontaneously hypertensive rats (SHRs), are susceptible to increased arterial blood pressure. We investigated whether chronic HgCl2 exposure in young SHRs accelerates hypertension development by studying the vascular function of mesenteric resistance arteries (MRAs) and SBP in young SHRs during the prehypertensive phase. Four-week-old male SHRs were divided into two groups: the SHR control group (vehicle) and the SHR HgCl2 group (4 weeks of exposure). The results showed that HgCl2 treatment accelerated the development of hypertension; reduced vascular reactivity to phenylephrine in MRAs; increased nitric oxide (NO) generation; promoted vascular dysfunction by increasing the production of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2); increased Gp91Phox protein levels and in situ levels of superoxide anion (O2·-); and reduced vasoconstrictor prostanoid production compared to vehicle treatment. Although HgCl2 accelerated the development of hypertension, the HgCl2-exposed animals also exhibited a vasoprotective mechanism to counterbalance the rapid increase in SBP by decreasing vascular reactivity through H2O2 and NO overproduction. Our results suggest that HgCl2 exposure potentiates this vasoprotective mechanism against the early establishment of hypertension. Therefore, we are concluding that chronic exposure to HgCl2 in prehypertensive animals could enhance the risk for cardiovascular diseases.


Assuntos
Pressão Arterial/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Hipertensão/induzido quimicamente , Cloreto de Mercúrio/toxicidade , Artérias Mesentéricas/efeitos dos fármacos , Óxido Nítrico/metabolismo , Animais , Modelos Animais de Doenças , Progressão da Doença , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Artérias Mesentéricas/metabolismo , Artérias Mesentéricas/fisiopatologia , NADPH Oxidase 2/metabolismo , Prostaglandinas/metabolismo , Ratos Endogâmicos SHR , Espécies Reativas de Oxigênio/metabolismo , Medição de Risco , Transdução de Sinais , Fatores de Tempo
19.
J Food Biochem ; 44(9): e13385, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-33460233

RESUMO

In this study, we assessed the protective effect of berberine (BBR) against mercuric chloride (HgCl2)-induced reproductive impairment. Twenty-eight adult male Wistar albino rats were placed into four equal groups: control, BBR, HgCl2, and BBR + HgCl2. All the treatments were orally administered for seven consecutive days. The rats exposed to HgCl2 showed a marked decrease in testosterone accompanied by an increase in lipid peroxidation (LPO) and nitric oxide (NO). Additionally, HgCl2 decreased glutathione (GSH) content, deactivated catalase (CAT) and glutathione reductase (GR), and suppressed the activities and mRNA expression of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the testicular tissue. In addition, histological deformations and testicular cell loss were recorded, as evidenced by the upregulation of caspase-3 following HgCl2 intoxication. Notably, BBR administration reversed the testicular impairments associated with HgCl2 exposure. These findings suggest that BBR protected the testicular tissue following HgCl2 exposure through inhibiting the disturbance in the testosterone level and enhanced the antioxidant capacity. PRACTICAL APPLICATIONS: Heavy metals are naturally existing metallic elements in the earth's crust. These trace metals have the potential to cause multiple adverse reactions to the living systems, even at low exposure doses. Human exposure may also result from industrial, agricultural, and domestic activities. Berberine (BBR, a naturally occurring quaternary benzylisoquinoline alkaloid) is a protoberberine and is the representative main active ingredient in all parts of Berberis species. BBR has been used widely in folk medicine worldwide for its multiple pharmacological and therapeutic activities; for example, in the treatment of digestive and reproductive system disorders, microorganism infections, hemorrhage and wound healing, and cardiovascular and ophthalmic diseases. We found that BBR administration was able to abrogate significantly the reproductive toxicity associated with Hg intoxication. This protective effect comes from its strong antioxidant, anti-inflammatory, and antiapoptotic activities; suggesting that BBR may be applied to alleviate reproductive toxicity associated with Hg intoxication.


Assuntos
Berberina , Mercúrio , Animais , Berberina/farmacologia , Cloretos , Masculino , Cloreto de Mercúrio/toxicidade , Estresse Oxidativo , Ratos , Ratos Wistar
20.
Oxid Med Cell Longev ; 2019: 5634685, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827681

RESUMO

Exposure to heavy metals, including mercury chloride (HgCl2), is associated with severe health problems. This study was designed to investigate HgCl2-induced nephrotoxicity and evaluate the protective role of Ziziphus spina-christi leaf extract (ZSCLE). Four randomly selected groups containing seven rats were used. For a period of 28 days, the control group was administered 0.9% saline solution; the second group was administered 300 mg/kg ZSCLE; the third group was administered 0.4 mg/kg HgCl2 dissolved in 0.9% physiological saline solution; and the fourth group was administered an oral supplement of 300 mg/kg ZSCLE one hour after HgCl2 administration. HgCl2 intoxication resulted in Hg accumulation in renal tissue; decreases in body weight, kidney index, and glutathione content and superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities; increases in creatinine, urea, Kim-1 expression, lipid peroxidation, and nitric oxide production; suppression of the Nrf2-antioxidant response pathway; upregulation of Il1ß, Tnfα, and Nos2; and potentiation of proapoptotic activity. ZSCLE exerted beneficial effects against mercury-induced renal toxicity and significantly reversed these alterations to near normal values. These effects resulted from its chelation and antioxidant, anti-inflammatory, and antiapoptotic activities. ZSCLE may prevent or minimize the pathological changes induced by mercury in the kidney.


Assuntos
Apoptose/efeitos dos fármacos , Cloreto de Mercúrio/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/farmacologia , Ziziphus/química , Animais , Catalase/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Creatinina/urina , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Fator 2 Relacionado a NF-E2/genética , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Folhas de Planta/química , Folhas de Planta/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Ziziphus/metabolismo
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