RESUMO
INTRODUCTION: The presence of mercury in the environment is a worldwide concern. Inorganic mercury is present in industrial materials, is employed in medical devices, is widely used in batteries, is a component of fluorescent light bulbs, and it has been associated with human poisoning in gold mining areas. The nephrotoxicity induced by inorganic mercury is a relevant health problem mainly in developing countries. The primary mechanism of mercury toxicity is oxidative stress. Trimetazidine (TMZ) is an anti-ischemic drug, which inhibits cellular oxidative stress, eliminates oxygen-free radicals, and improves lipid metabolism. The aim of this study was to evaluate whether the administration of TMZ protects against mercuric chloride (HgCl2) kidney damage. METHODS: Adult male Wistar rats received only HgCl2 (4 mg/kg bw, sc) (Hg group, n = 5) or TMZ (3 mg/kg bw, ip) 30 min before HgCl2 administration (4 mg/kg bw, sc) (TMZHg group, n = 7). Simultaneously, a control group of rats (n = 4) was studied. After 4 days of HgCl2 injection, urinary flow, urea and creatinine (Cr) plasma levels, Cr clearance, urinary glucose, and sodium-dicarboxylate cotransporter 1 (NaDC1) in urine were determined. Lipid peroxidation (MDA) and glutathione (GSH) levels were measured in kidney homogenates. RESULTS: Rats only treated with HgCl2 showed an increase in urea and Cr plasma levels, urinary flow, fractional excretion of water, glucosuria, and NaDC1 urinary excretion as compared with the control group and a decrease in Cr clearance. TMZHg group showed a decrease in urea and Cr plasma levels, urinary flow, fractional excretion of water, glucosuria, NaDC1 urinary excretion, and an increase in Cr clearance when compared to the Hg group. Moreover, MDA and GSH levels observed in Hg groups were decreased and increased, respectively, by TMZ pretreatment. CONCLUSION: TMZ exerted a renoprotective action against HgCl2-induced renal injury, which might be mediated by the reduction of oxidative stress. Considering the absence of toxicity of TMZ, its clinical application against oxidative damage due to HgCl2-induced renal injury should be considered. The fact that TMZ is commercially available should simplify and accelerate the translation of the present data "from bench to bedside." In this context, TMZ become an interesting new example of drug repurposing.
Assuntos
Nefropatias/prevenção & controle , Intoxicação por Mercúrio/prevenção & controle , Substâncias Protetoras/farmacologia , Trimetazidina/farmacologia , Animais , Creatinina/sangue , Transportadores de Ácidos Dicarboxílicos/urina , Glutationa/metabolismo , Glicosúria/induzido quimicamente , Glicosúria/prevenção & controle , Nefropatias/induzido quimicamente , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Cloreto de Mercúrio/efeitos adversos , Transportadores de Ânions Orgânicos Dependentes de Sódio/urina , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Ratos Wistar , Cloreto de Sódio/urina , Simportadores/urina , Trimetazidina/uso terapêutico , Ureia/sangue , Micção/efeitos dos fármacosRESUMO
Mercury is a widespread pollutant. Mercuric ions uptake into tubular cells is supported by the Organic anion transporter 1 (Oat1) and 3 (Oat3) and its elimination into urine is through the Multidrug resistance-associated protein 2 (Mrp2). We investigated the effect of recombinant human erythropoietin (Epo) on renal function and on renal expression of Oat1, Oat3, and Mrp2 in a model of mercuric chloride (HgCl2)-induced renal damage. Four experimental groups of adult male Wistar rats were used: Control, Epo, HgCl2, and Epo + HgCl2. Epo (3000 IU/kg, b.w., i.p.) was administered 24 h before HgCl2 (4 mg/kg, b.w., i.p.). Experiments were performed 18 h after the HgCl2 dose. Parameters of renal function and structure were evaluated. The protein expression of Oat1, Oat3 and Mrp2 in renal tissue was assessed by immunoblotting techniques. Mercury levels were determined by cold vapor atomic absorption spectrometry. Pretreatment with Epo ameliorated the HgCl2-induced tubular injury as assessed by histopathology and urinary biomarkers. Immunoblotting showed that pretreatment with Epo regulated the renal expression of mercury transporters in a way to decrease mercury content in the kidney. Epo pretreatment ameliorates HgCl2-induced renal tubular injury by modulation of mercury transporters expression in the kidneys.
Assuntos
Eritropoetina/uso terapêutico , Nefropatias/tratamento farmacológico , Cloreto de Mercúrio/toxicidade , Substâncias Protetoras/uso terapêutico , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Eritropoetina/genética , Eritropoetina/farmacologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Mercúrio/sangue , Mercúrio/metabolismo , Mercúrio/urina , Proteína 1 Transportadora de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo , Substâncias Protetoras/farmacologia , Ratos Wistar , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Ureia/sangueRESUMO
Mercury is a metal which is potentially toxic for the environment. Many factors control its retention in the soil, such as cation exchange capacity, pH, clay content, organic matter, and redox potential. It is important to know the phytotoxic effects of soil Hg to prevent environmental contamination and its entry into the food chain. Several analytical methods are used to measure metal phytoavailability in soils, but none has been reported for Hg in Oxisols, the most common soil class in Brazil and a very important soil class throughout the tropics. The aim of this study was to select the chemical extractor that best correlated the Hg levels in plants and the Oxisols. The soils used were classified as Dystrophic Red-Yellow Oxisol (LVAd) and Dystroferric Red Oxisol (LVdf), which were collected in the 0-0.2-m soil layer. The species selected for cultivation were a monocotyledon, oat (Avena sativa L. cv. São Carlos) and a eudicotyledon, common bean (Phaseolus vulgaris L. cv. Madrepérola). Each test plot was composed of a 500 cm3 pot filled with soil samples contaminated with HgCl2. Treatments were arranged in a completely randomized design, with four replications. The experiment was conducted for 30 days. Mercury contents were separately extracted with the following extractors: USEPA 3051A, Mehlich-1, Mehlich-3, DTPA, and water. Mercury was determined by hydride generation atomic absorption spectroscopy. The extracted contents were correlated with the contents in the tissues of the plants' aerial part by the Pearson correlation. Although it is not considered a standard procedure to evaluate metal phytoavailable contents, the method that presented the best correlations between soil Hg and plant Hg was USEPA 3051A (r = 0.75*). As expected, the worst correlation was with water (r = 0.57* for common bean and r = 0,05ns for oat).
Assuntos
Monitoramento Ambiental , Mercúrio/análise , Poluentes do Solo/análise , Solo/química , Brasil , Metais , Espectrofotometria AtômicaRESUMO
Mercuric ions (Hg+2) gain access to proximal tubule cells primarily by the Organic Anion Transporter 1 (Oat1) and 3 (Oat3) in the basolateral plasma membrane. The removal process of Hg+2 ions from cells into the lumen involves an efflux process mainly mediated by the Multidrug Resistance-Associated Protein 2 (Mrp2). The aim of this study was to compare the sex-related differences in the renal expression of Oat1, Oat3, and Mrp2 after mercuric chloride (HgCl2) treatment and analyze their relevance in the mercury-induced nephrotoxicity. Control and Hg-treated male and female Wistar rats were used. Animals received a dose of HgCl2 (4 mg/kg bw, ip) 18 h before the experiments. Tubular injury was assessed by histopathological studies. The renal expression of Oat1, Oat3, and Mrp2 was analyzed by Western Blotting. Mercury levels were determined in urine by cold vapour atomic absorption spectroscopy. HgCl2 treatment increased the expression of renal Oat1 and Mrp2 in both sexes, being more evident in females than in males. The Oat3 renal expression only increased in female rats. The higher expressions of Oat1, Oat3, and Mrp2 could explain the higher renal excretion of mercury and consequently, the lesser renal tubular damage in female rats than in male rats.
Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Poluentes Ambientais/toxicidade , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Cloreto de Mercúrio/toxicidade , Proteína 1 Transportadora de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo , Animais , Poluentes Ambientais/urina , Feminino , Rim/metabolismo , Rim/patologia , Nefropatias/patologia , Nefropatias/urina , Masculino , Cloreto de Mercúrio/urina , Ratos Wistar , Eliminação Renal , Índice de Gravidade de Doença , Fatores SexuaisRESUMO
The accumulation of mercury in the liver causes hepatotoxicity. The organic anion transporter 3 (Oat3) and the multidrug-resistance associated protein 2 (Mrp2) are involved in the hepatic excretion of toxins and drugs and in the hepatic handling of mercury. The aim of this work was to study if there are gender-related differences in mercuric chloride (HgCl2)-induced hepatotoxicity in rats. Total mercury levels and protein expressions of Oat3 and Mrp2 in liver samples were also assessed to clarify the mechanisms underlying mercury-induced liver damage in male and female rats. Control and HgCl2-treated male and female Wistar rats were used. Hepatotoxicity was evaluated by plasma activity of transaminases and alkaline phosphatase, as well as by histopathological analysis. Oat3 and Mrp2 expression was assessed by immunoblotting. Female rats displayed a higher HgCl2-induced hepatotoxicity than male rats as demonstrated by the higher alterations in the plasma markers of liver damage and in the histopathology. The sex-related differences observed in the hepatic damage can be explained by the higher accumulation of mercury in liver from female rats. In this connection, after mercury treatment the expression of Mrp2 decreased in both sexes and the expression of Oat3 decreased only in males. The decreased in Oat3 abundance in the hepatocytes membranes in mercury-treated males would limit the uptake of mercuric ions into the liver protecting them from mercury hepatotoxicity.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/patologia , Fígado/patologia , Mercúrio/toxicidade , Animais , Biomarcadores/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Feminino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Fatores SexuaisRESUMO
Mercury chloride exposure for 30 days decreases NO bioavailability and increases oxidative stress. However, the mechanisms underlying the effects of mercury on the cardiovascular system are not completely understood, and it is not known if they are dose-dependent or if some concentrations have no harmful effects. Thus, we investigated the effects of chronic exposure to doses low (half) and high (2.5-fold higher) than that needed to obtain 29 nmol/L of HgCl2 on the vascular function. Three-month-old male Wistar rats received intramuscular (i.m.) HgCl2 for 30 days and were divided in three groups: lower (Low Hg); higher (High Hg); and saline was used as the control. High Hg exposure increased the contractile response to phenylephrine (PHE) in aortic rings, but Low Hg reduced it. The hyporesponsiveness in the Low Hg rats was blunted by endothelial denudation and NOS inhibition with l-NAME (100 µmol/L). The phosphorylated-eNOS/eNOS protein ratio increased in the aortas of Low Hg rats. In the High Hg group, endothelial denudation increased the PHE-induced contractions, while l-NAME had no effects and indomethacin (10 µmol/L), losartan (10 µmol/L) and apocynin (30 µmol/L) reduced this response. In the High Hg group, protein levels of the NADPH oxidase subunit gp91phox and cyclooxygenase-2 increased. Our results support previous suggestions that High Hg increases oxidative stress that might activate an inflammatory cascade and the renin-angiotensin system. However, very low Hg concentrations below the level considered safe still reduced vascular reactivity, suggesting the need for special attention to continuous exposure as a putative cause of increased cardiovascular risk.
Assuntos
Aorta/efeitos dos fármacos , Mercúrio/efeitos adversos , Animais , Aorta/metabolismo , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/metabolismo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Masculino , Cloreto de Mercúrio/efeitos adversos , NADPH Oxidases/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Fatores de Risco , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacologiaRESUMO
Mercuric chloride (HgCl2) induces kidney damage, in part, through oxidative stress. A role for angiotensin II (Ang II) in pro-inflammatory events in a model of acute HgCl2-induced nephropathy was reported. Ang II is a potent oxidative stress inducer; however, its role in oxidative/anti-oxidative events in HgCl2-induced nephropathy remains unknown. The aim of this study was to determine the role of Ang II in the oxidative stress and renal infiltration of CD8(+) T-cells after an acute HgCl2 intoxication. Three groups of Sprague Dawley rats were treated with a single subcutaneous dose of 2.5 mg/kg HgCl2: for 3 days prior to and for 4 days after that injection, rats in one group received Losartan (30 mg/kg), in another group Enalapril (30 mg/kg) or normal saline in the last group. Two other groups of drug-treated rats received saline in place of HgCl2. A final group of rats received saline in place of HgCl2 and the test drugs. All treatments were via gastric gavage. At 96 h after the vehicle/HgCl2 injection, blood and kidney samples were harvested. Renal sections were homogenized for measures of malondialdehyde (MDA), reduced glutathione (GSH) and catalase activity. Frozen sections were studied for the presence of superoxide anion ([Formula: see text]) and CD8(+) T-cells. HgCl2-treated rats had increased interstitial and tubular expression of [Formula: see text], high levels of MDA, normal catalase activity and GSH content, increased levels of interstitial CD8(+) T-cells and an increased percentage of necrotic tubules. Anti-Ang II treatments diminished the HgCl2-induced increases in interstitial [Formula: see text], CD8(+) T-cells and tubular damage and increased catalase and GSH expression above that due to HgCl2 alone; the HgCl2-induced high MDA levels were unaffected by the drugs. These data provide new information regarding the potential role of Ang II in the oxidative stress and renal CD8(+) T-cell infiltration that occur during HgCl2 nephropathy.
Assuntos
Angiotensina II/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Nefropatias/imunologia , Rim/metabolismo , Cloreto de Mercúrio/administração & dosagem , Estresse Oxidativo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Animais , Linfócitos T CD8-Positivos/imunologia , Catalase/metabolismo , Enalapril/administração & dosagem , Glutationa/metabolismo , Rim/imunologia , Rim/patologia , Nefropatias/induzido quimicamente , Losartan/administração & dosagem , Masculino , Malondialdeído/metabolismo , Cloreto de Mercúrio/toxicidade , Necrose , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
The aim of the present study was to elucidate the possible protective role of vitamin E and / or sodium selenite on mercuric chloride-induced oxidative stress and histopathological changes in the lung tissue of the rats. Adult male albino Wistar rats were exposed to mercuric chloride (1.0 mg/kg day) for four weeks. Treatment with mercuric chloride led to oxidative stress by enhancing MDA level and also decreasing superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx) and glutathione S transferaz (GST) activities. However, mercuric chloride exposure resulted in histopathological changes in the lung tissue in the rats. MDA level and SOD, CAT GPx and GST activities and histopathological changes modulated in concomitantly supplementation of vitamin E (100 mg/kg day) and /or sodium selenite (0.25 mg/kg day) to mercuric chloride-treated groups.
RESUMO
This study was designed to investigate the protective effects of sodium selenite and/or vitamin E against mercuric chloride-induced cardiotoxicity. Male Wistar rats (n=48, 310±10 g) were administered mercuric chloride (1.0 mg/kg bw), sodium selenite (0.25 mg/kg bw), vitamin E (100 mg/kg bw), sodium selenite plus mercuric chloride, vitamin E plus mercuric chloride and sodium selenite plus vitamin E plus mercuric chloride daily via gavage for four weeks. Malondialdehyde (MDA) level, antioxidant enzyme activities [total superoxide dismutase (SOD), catalase (CAT), total glutathione peroxidase (GPx) and total glutathione-S-transferase (GST)], and histopathological changes in the heart tissue were evaluated. Results showed that mercuric chloride exposure resulted in an increase in the MDA level and a decrease in the SOD, CAT, GPx and GST activities, with respect to the control. Light microscopic investigations revealed that mercuric chloride induced histopathological changes in the heart tissue. A significant decrease in the MDA level and a significant increase in the SOD, CAT, GPx and GST activities were observed on the supplementation of sodium selenite and/or vitamin E to mercuric chloride-treated rats, which showed that, sodium selenite and/or vitamin E significantly reduced mercuric chloride induced cardiotoxicity, but not protected completely.
RESUMO
Resumen El mercurio es un contaminante xenobiótico encontrado frecuentemente en ecosistemas naturales, representando un aspecto relevante en salud pública y ambiental debido a los niveles encontrados en fuentes de agua en correlación con la bioacumulación en organismos vivos. El objetivo fue evaluar los efectos inmunotoxicológicos e histopatológicos de la exposición a concentraciones subletales de Cloruro de Mercurio (HgCl2) en cachama blanca (Piaractus brachypomus). Se utilizaron alevinos de cachama blanca, con un peso de 10 ± 2,1 g, distribuidos en acuarios con aireación constante, sin filtro. El periodo experimental fue de 18 días, utilizando 4 concentraciones basadas en la décima parte de la CL50 descrita para cachama, así como un grupo control. Se realizaron seis muestreos (días 1, 2, 4, 7, 12 y 18) en los cuales se tomaron muestras de sangre para la evaluación de la explosión respiratoria y la capacidad bactericida del plasma. Se calculó el índice hepatosomático y se tomaron muestras para procesamiento histopatológico. Se evidenció una elevación del nivel de explosión respiratoria (estrés oxidativo) en animales expuestos a HgCl2 de una manera dependiente de la concentración, siendo más marcado este efecto al día 12 de exposición. No se encontraron diferencias significativas en los valores de índice hepatosomático (IHS). En la actividad bactericida del plasma se halló una actividad menor en animales expuestos a HgCl2. En el análisis histopatológico se encontraron cambios como hiperplasia, aneurismas y sinequias en branquias; inclusiones hialinas en hígado y centros melanomacrófagos en riñón. Los alevinos de cachama blanca expuestos a dosis subletales de HgCl2, muestran un incremento significativo en la explosión respiratoria (estrés oxidativo), así como cambios en la actividad bactericida del plasma, además de cambios anatomopatológicos a nivel branquial, hepático y renal.
Mercury is a xenobiotic contaminant often found in natural ecosystems. It is relevant for public and environmental health because of the existing correlation between its content in water sources and mercury bioaccumulation in living organisms. This work assessed the immune and histopathological effects of exposure to sublethal concentrations of mercury chloride (HgCl2) in Pacu (Piaractus brachypomus). Pacu fingerlings weighing 10 ± 2.1 g were distributed in constantly aerated tanks with no filter. The experimental period was 18 days. A negative control group and four Hg levels were used based on the tenth of LC50 for Pacu. Six blood samples were taken on days 1, 2, 4, 7, 12 and 18 to measure respiratory burst and bactericidal activity of the plasma. The hepatosomatic index was calculated and samples were taken for histopathological examination. Increased respiratory burst (oxidative stress) was observed in animals exposed to HgCl2 in a concentration-dependent manner. This effect was more pronounced at day 12 of exposure. Hepatosomatic index (HSI) values showed no significant differences. Animals exposed to HgCl2 showed low bactericidal activity of plasma. Histopathological changes such as hyperplasia, aneurysms and synechiae were found in gills, while hyaline inclusions were observed in liver and melanomacrophage centers in kidney. Pacu fingerlings exposed to sublethal doses of HgCl2 had a significant increase in oxidative stress and changes in plasma bactericidal activity in addition to pathological changes in the gills, hepatic and renal tissues.
O mercúrio é um contaminante xenobiótico encontrado frequentemente nos ecossistemas naturais, o qual representa um aspecto muito importante na saúde pública e ambiental devido aos níveis encontrados nas fontes de agua, as quais além, tem correlação com a bioacumulação em organismos vivos. O objetivo desta pesquisa foi avaliar os efeitos imunotoxicológicos e histopatológicos da exposição a concentrações subletais de Cloreto de Mercúrio (HgCl2) em Pirapitinga branca (Piaractus brachypomus). Utilizaram-se alevinos de Pirapitinga branca com um peso médio de 10 ± 2,1 g, distribuídos em aquários com tanques de aireação constante sem filtro. O período experimental foi de 18 dias, utilizando quatro concentrações baseadas na decima parte da CL50 descrita para Pirapitinga branca assim como no grupo controle. Realizaram-se seis amostragens (dias 1, 2, 4, 7, 12 e 18) nos quais tomaram-se amostras de sangue para a avaliação da explosão respiratória e a capacidade bactericida do plasma. Calculou-se o índice hepatosomático e pegaram-se amostras para processamento histopatológico. Evidenciou-se uma elevação do nível de explosão respiratória (estresse oxidativo) em animais expostos ao HgCl2 de uma maneira dependente da concentração, sendo mais marcado este efeito ao dia 12 da exposição. Não se encontraram diferenças significativas nos valores do índice hepatosomático (IHS). Na atividade bactericida do plasma achou-se uma atividade menor em animais expostos ao HgCl2. Na análise histopatológica encontraram-se mudanças como hiperplasia, aneurisma e sinéquias em brânquias, inclusões hialinas no fígado e centros melanomacrófagos nos rins. Os alevinos de Pirapitinga branca expostos a doses sub-letais de HgCl2, amostraram um incremento significativo na explosão respiratória (estresse oxidativo) assim como mudanças na atividade bactericida do plasma, além de mudanças anatomopatológicas no nível branquial, hepático e renal.
RESUMO
This study evaluated the effects of HgCl2 on renal parameters in nonlactating and lactating rats and their pups, as well as the preventive role of ZnCl2 . Rats received 27 mg kg(-1) ZnCl2 for five consecutive days and 5 mg kg(-1) HgCl2 for five subsequent days (s.c.). A decrease in δ-aminolevulinic acid dehydratase (δ-ALA-D) activity in the blood and an increase in urine protein content in renal weight as well as in blood and urine Hg levels were observed in lactating and nonlactating rats from Sal-Hg and Zn-Hg groups. ZnCl2 prevented partially the δ-ALA-D inhibition and the proteinuria in nonlactating rats. Renal Hg levels were increased in all HgCl2 groups, and the ZnCl2 exposure potentiated this effect in lactating rats. Nonlactating rats exposed to HgCl2 exhibited an increase in plasma urea and creatinine levels, δ-ALA-D activity inhibition and histopathological alterations (necrosis, atrophic tubules and collagen deposition) in the kidneys. ZnCl2 exposure prevented the biochemical alterations. Hg-exposed pups showed lower body and renal weight and an increase in the renal Hg levels. In conclusion, mercury-induced nephrotoxicity differs considerably between lactating and nonlactating rats. Moreover, prior exposure with ZnCl2 may provide protection to individuals who get exposed to mercury occupationally or accidentally.
Assuntos
Cloretos/farmacologia , Rim/efeitos dos fármacos , Cloreto de Mercúrio/toxicidade , Compostos de Zinco/farmacologia , Animais , Nitrogênio da Ureia Sanguínea , Peso Corporal/efeitos dos fármacos , Creatinina/sangue , Feminino , Rim/metabolismo , Rim/patologia , Lactação , Mercúrio/sangue , Sintase do Porfobilinogênio/metabolismo , Proteínas/análise , Ratos , Ratos Wistar , Zinco/sangueRESUMO
Bilitranslocase (BTL) is a plasma membrane carrier that transports organic anions of physiological and pharmacological interest. It is expressed in basolateral plasma membrane of kidney and liver. BTL has been recently described as a marker of transition from normal tissue to its neoplastic transformation in human kidney. Inorganic mercury is a major environmental contaminant that produces many toxic effects. Previous reports have described an interaction between BTL and mercuric ions. This study was designed to evaluate the renal and hepatic expression of BTL in rats exposed to a nephrotoxic and hepatotoxic dose of HgCl2. Male rats were treated with a single injection of HgCl2 at a dose of 4mg/kg body wt, i.p. (HgCl2 group). Control rats received the vehicle alone (Control group). Studies were carried out 18h after injection. Afterwards, the kidneys and livers were excised and processed for histopathological studies or immunoblot (homogenates and crude membranes) techniques. In rats treated with HgCl2, immunoblotting showed a significant decrease in the abundance of BTL in homogenates and plasma membranes from kidney and liver. BTL decrease of expression might reflect the grade of damage in renal tubule cells and in hepatocytes. Thus, BTL might be postulated as a new biomarker of tissue toxicity induced by mercury.
Assuntos
Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Cloreto de Mercúrio/toxicidade , Animais , Aspartato Aminotransferases/sangue , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Ceruloplasmina , Regulação da Expressão Gênica , Rim/enzimologia , Fígado/enzimologia , Masculino , Proteínas de Membrana/genética , Mercúrio/urina , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
The aim of this study was to determine if there are sex-related differences in the acute kidney injury induced by HgCl(2) since female rats express lower levels of renal Oat1 and Oat3 (transporters involved in renal uptake of mercury) as compared with males. Control males and females and Hg-treated male and female Wistar rats were employed. Animals were treated with HgCl(2) (4 mg/kg body weight (b.w.), intraperitoneal (i.p.)) 18 h before the experiments. HgCl(2) induced renal impairment both in male and female rats. However, female rats showed a lower renal impairment than male rats. The observed increase in kidney weight/body weight ratio seen in male and female rats following HgCl(2) treatment was less in the female rats. Urine volume and creatinine clearance decreased and Oat5 urinary excretion increased in both males and females, but to a lesser degree in the latter. Urinary alkaline phosphatase (AP) activity and histological parameters were modified in male but not in female rats after HgCl(2) administration. These results indicate that the lower Oat1 and Oat3 expression in the kidney of females restricts Hg uptake into renal cells protecting them from this metal toxicity. These gender differences in renal injury induced by mercury are striking and also indicate that Oat1 and Oat3 are among the main transporters responsible for HgCl(2)-induced renal injury.