RESUMO
According to data from studies, antioxidant herbal compounds are, likely to have a useful role in reducing the harmful effects of environmental pollutants and toxic chemicals that most people are exposed to. Cadmium is one of the toxic elements that accumulate in many organs, especially in kidneys. The aim of this study was to investigate the effect of crocin on the expression of PKHD1 and KLLN genes in cadmium-treated rats.In this experimental study, 40 adults male Wistar rats (200-250 g) were randomly divided into the following groups: control group received normal saline, cadmium group (15mg/kg), crocin group (20mg/kg) and cadmium group daily fed with crocin at a dose of 20 mg/kg.After eight weeks of treatment, rats were dissected, and kidney tissues were removed for evaluation of PKHD1 and KLLN gene expression by real time method. The data were analyzed using one-way ANOVA and significant difference between groups was P<0.05.Our results showed an increase in PKHD1 gene expression and a decrease in KLLN gene expression in kidney tissue in the cadmium group compared to the control group (P <0.001).Also, a significant decrease in PKHD1 gene expression (P <0.001) and an increase in KLLN gene expression P <0.05) were observed in the tissues of all cadmium-treated rats compared to cadmium.Crocin consumption can have a protective effect against the impaired expression of PKHD1 and KLLN cadmium-induced apoptotic pathway.
Diversos estudios sugieren que compuestos antioxidantes de hierbas tienen un papel útil en la reducción de los efectos nocivos de los contaminantes ambientales y los químicos tóxicos a los que está expuesta la mayoría de las personas. El cadmio es uno de los elementos tóxicos que se acumulan en muchos órganos, especialmente en los riñones. El objetivo de este estudio fue investigar el efecto de la crocina en la expresión de los genes PKHD1 y KLLN en ratas tratadas con cadmio.En este estudio experimental, 40 ratas Wistar macho adultas (200-250 g) se dividieron aleatoriamente en los siguientes grupos: el grupo de control recibió solución salina normal, el grupo de cadmio (15 mg / kg), el grupo de crocina (20 mg / kg) y el grupo de cadmio alimentado diariamente con crocina a una dosis de 20 mg / kg.Después de ocho semanas de tratamiento, se disecaron las ratas y se extrajeron los tejidos renales para evaluar la expresión de los genes PKHD1 y KLLN mediante un método en tiempo real. Los datos se analizaron mediante ANOVA de una vía y la diferencia significativa entre los grupos fue P <0,05.Nuestros resultados mostraron un aumento en la expresión del gen PKHD1 y una disminución en la expresión del gen KLLN en el tejido renal en el grupo de cadmio en comparación con el grupo de control (P <0,001).Además, se observó una disminución significativa en la expresión del gen PKHD1 (P <0,001) y un aumento en la expresión del gen KLLN P <0,05) en los tejidos de todas las ratas tratadas con cadmio en comparación con el cadmio.El consumo de crocina puede tener un efecto protector contra la expresión alterada de la vía apoptótica inducida por cadmio PKHD1 y KLLN.
Assuntos
Animais , Ratos , Cádmio/uso terapêutico , Carotenoides/farmacologia , Receptores de Superfície Celular/genética , Proteínas Supressoras de Tumor/genética , Ratos Wistar , Neoplasias Renais/tratamento farmacológicoRESUMO
Cadmium (Cd) precipitation and dissolution in pore water is associated with dissolved organic carbon (DOC)-induced reduction-oxidation of sulfur (S) under waterlogging and is vital for controlling the bioavailability in paddy soil. A 120-day soil incubation experiment, including application of sulfur (S, 30â¯mgâ¯kg-1) and wheat straw (W, 1.0%) alone or in combination (W + S) into Cd-contaminated paddy soil under waterlogging, was conducted to investigate the dynamic of dissolved Cd and its relationship with DOC, S2-, Fe2+, pH, Eh and pe + pH in soil pore water. The results showed that the lowest dissolved Cd concentration was observed in the W + S-treated soil pore water among all treatments when the soil Eh remained at lower values during the period of 15-60 days of incubation, which could be attributed to CdS precipitation and/or co-precipitation of Cd absorbed by FeS2 because of the reduction in sulfur. The application of S resulted in a Cd rebound in the pore water irrespective of W addition when the Eh began to increase from its lowest values during the period of 45-75 days of incubation, and SOB genera were observed in the S added soil. This could be attributed to re-dissolution of the precipitated Cd in soils under the SOB-driven oxidation of sulfide such as CdS and FeS2. In conclusion, DOC-driven reduction-oxidation of sulfur controls Cd dissolution in the pore water of Cd-contaminated paddy soil under waterlogging conditions. Further studies are required to investigate the interaction of sulfur and SOM-induced DOC on Cd bioavailability in rice-planted paddy soils.
Assuntos
Cádmio/uso terapêutico , Poluição Ambiental/efeitos adversos , Poluentes do Solo/química , Enxofre/uso terapêutico , Cádmio/farmacologia , Enxofre/farmacologia , ÁguaRESUMO
Phytoremediation soil polluted by cadmium has drawn worldwide attention. However, how to improve the efficiency of plant remediation of cadmium contaminated soil remains unknown. Previous studies showed that nitrogen (N) significantly enhances cadmium uptake and accumulation in poplar plants. In order to explore the important role of nitrogen in plants' responses to cadmium stress, this study investigates the poplar proteome and phosphoproteome difference between Cd stress and Cd + N treatment. In total, 6573 proteins were identified, and 5838 of them were quantified. With a fold-change threshold of > 1.3, and a p-value < 0.05, 375 and 108 proteins were up- and down-regulated by Cd stress when compared to the control, respectively. Compared to the Cd stress group, 42 and 89 proteins were up- and down-regulated by Cd + N treatment, respectively. Moreover, 522 and 127 proteins were up- and down-regulated by Cd + N treatment compared to the CK group. In addition, 1471 phosphosites in 721 proteins were identified. Based on a fold-change threshold of > 1.2, and a p-value < 0.05, the Cd stress up-regulated eight proteins containing eight phosphosites, and down-regulated 58 proteins containing 69 phosphosites, whereas N + Cd treatment up-regulated 86 proteins containing 95 phosphosites, and down-regulated 17 proteins containing 17 phosphosites, when compared to Cd stress alone. N + Cd treatment up-regulated 60 proteins containing 74 phosphosites and down-regulated 37 proteins containing 42 phosphosites, when compared to the control. Several putative responses to stress proteins, as well as transcriptional and translational regulation factors, were up-regulated by the addition of exogenous nitrogen following Cd stress. Especially, heat shock protein 70 (HSP70), 14-3-3 protein, peroxidase (POD), zinc finger protein (ZFP), ABC transporter protein, eukaryotic translation initiation factor (elF) and splicing factor 3 B subunit 1-like (SF3BI) were up-regulated by Cd + N treatment at both the proteome and the phosphoproteome levels. Combing the proteomic data and phosphoproteomics data, the mechanism by which exogenous nitrogen can alleviate cadmium toxicity in poplar plants was explained at the molecular level. The results of this study will establish the solid molecular foundation of the phytoremediation method to improve cadmium-contaminated soil.
Assuntos
Cádmio/uso terapêutico , Nitrogênio/farmacologia , Fosfoproteínas/metabolismo , Proteínas de Plantas/metabolismo , Populus/metabolismo , Proteoma/metabolismo , Fosforilação/efeitos dos fármacosRESUMO
A cintilografia miocárdica de perfusão (CMP) é um dos métodos mais utilizados na avaliação de pacientes com suspeita de coronariopatia por seu valor diagnóstico e prognóstico. Duas de suas maiores limitações são o uso de radiação e a duração prolongada dosexames. Entretanto, novas Gamacâmaras de CZT (GC-CZT) têm permitido reduzir as doses dos radiotraçadores empregadas e o tempo de aquisição. O valor prognóstico desses novos protocolos não é conhecido.Objetivo: Determinar o valor prognóstico de um novo protocolo de CMP ultrarrápido e de baixa radiação numa GC-CZT. População: Pacientes com suspeita de coronariopatia consecutivamente submetidos a CMP numa GC-CZT no período de novembro de 2011 a junho de 2012.Metodologia: Foi utilizado protocolo de mesmo dia, iniciado pela fase de repouso com dose de 5 mCi e posterior estresse com dose de 15 mCi de Tc-99m sestamibi. Os tempos de aquisição foram de 6 e 3 minutos, respectivamente. Os exames foram classificados como normais ou anormais e escores de perfusão (SSS, SRS e SDS) foram calculados. Pacientes foram acompanhados mediante contato telefônico semestral. Os eventos avaliados foram morte, infarto não fatal e revascularização tardia (> 60 dias após CMP). Foi utilizado método de Coxpara identificar os preditores.Resultados: Setecentos e noventa e dois pacientes foram acompanhados por 21,3 ± 3,7 meses. A idade média foi de 65,2 ± 12,7 anos, sendo 50,3% do sexo masculino e o IMC médio de 26,9 ± 4,7. Hipertensão arterial foi o fator de risco mais frequente (59,5%), seguidode dislipidemia (51,9%) e diabetes (23,3%). Estresse físico foi empregado em 438 (55,3%) pacientes; 618 (78%) CMP foram normais. A dosimetria média dos exames foi 6 mSv e a duração média, de 48 ± 11 minutos. Durante o seguimentos ocorreram 12 óbitos, 4 infartos não fatais...
Myocardial perfusion scintigraphy (MPS) is one of the most used imaging methods for the evaluation of patients for coronary artery disease (CAD) due to its diagnostic and prognostic value. Two of its main limitations are radiation use and scan duration. However, CZT cameras (CZT-C) have allowed tracer dose and scan time reductions. However, the prognostic value of these new protocols is not known. Objective: To determine the prognostic value of a new, ultrafast, low dose protocol in a CZT-C. Population: Patients with suspect CAD undergoing MPS from 11/2011 to 6/2012 were studied. Methods: They had a 1-day Tc-99m sestamibi protocol starting with rest study (5 mCi dose) followed by stress (15 mCi). Acquisition times were 6 and 3 minutes respectively. MPS studied were classified as normal or abnormal and perfusion scores (SSS, SRS and SDS) were calculated. Patients were accompanied by 6-month phone calls. Events were defined as death, nonfatal myocardial infarction and late revascularization (> 60 days after MPS) and analyzed with the Cox method.Results: 792 patients were followed for 21.3 ± 3.7 months. Age was 65.2 ± 12.7 years, 50.3% were male and body mass index was 26.9 ± 4.7. Hypertension was the most frequent risk factor (59.5%), followed by hypercholesterolemia (51.9%) and diabetes (23.3%). Exercise was used in 438 (55.3%); 618 (78%) MPS studies were normal. Mean dosimetry was 6 mSv and mean scan time, 48 ± 11 minutes. During follow-up, there were 12 deaths...
Assuntos
Humanos , Masculino , Feminino , Idoso , Doenças das Artérias Carótidas , Câmaras gama , Imagem de Perfusão do Miocárdio/métodos , Prognóstico , Controle da Exposição à Radiação , Semicondutores/tendências , Cádmio/uso terapêutico , Compostos Radiofarmacêuticos/administração & dosagem , Fatores de Risco , Interpretação Estatística de Dados , Telúrio , Resultado do Tratamento , Telúrio/uso terapêutico , Zinco/uso terapêuticoRESUMO
Cadmium, a highly persistent heavy metal, has been categorized as a human carcinogen. Even though it is known that cadmium acts as estrogens in breast cancer cells, several studies failed to demonstrate whether cadmium is a causal factor for breast cancer. The lack of a strong association between cadmium and breast cancer could be found in the antiangiogenic properties of this heavy metal, which might counteract its carcinogenic properties in the progression of breast cancer. In this study, we exposed estrogen-responsive breast cancer cells to subtoxic levels of cadmium, and we evaluated their angiogenic potential using the chick embryo chorioallantoic membrane assay. Exposure of breast cancer cells to subtoxic levels of cadmium significantly inhibited the angiogenic potential of the breast cancer cell line, suggesting the possibility that cadmium might negatively regulate the production of proangiogenic factors in breast cancer cells. Our results suggest that cadmium might exert a paradoxical effect in breast cancer: on the one hand, it could promote carcinogenesis, and, on the other hand, it could delay the onset of tumors by inhibiting breast cancer cell-induced angiogenesis.
Assuntos
Inibidores da Angiogênese/farmacologia , Neoplasias da Mama/tratamento farmacológico , Cádmio/farmacologia , Carcinógenos/farmacologia , Neovascularização Patológica/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Animais , Neoplasias da Mama/patologia , Cádmio/uso terapêutico , Linhagem Celular Tumoral , Embrião de Galinha , Membrana Corioalantoide/irrigação sanguínea , Membrana Corioalantoide/efeitos dos fármacos , Feminino , HumanosRESUMO
The field of nanotechnology is rapidly expanding with the development of novel nanopharmaceuticals that have potential for revolutionizing medical treatment. The rapid pace of expansion in this field has exceeded the pace of pharmacological and toxicological research on the effects of nanoparticles in the biological environment. The development of cadmium-containing nanoparticles, known as quantum dots, show great promise for treatment and diagnosis of cancer and targeted drug delivery, due to their size-tunable fluorescence and ease of functionalization for tissue targeting. However, information on pharmacology and toxicology of quantum dots needs much further development, making it difficult to assess the risks associated with this new nanotechnology. Further, nanotechnology poses yet another risk for toxic cadmium, which will now enter the biological realm in nano-form. In this review, we discuss cadmium-containing quantum dots and their physicochemical properties at the nano-scale. We summarize the existing work on pharmacology and toxicology of cadmium-containing quantum dots and discuss perspectives in their utility in disease treatment. Finally, we identify critical gaps in our knowledge of cadmium quantum dot toxicity, and how these gaps need to be assessed to enable quantum dot nanotechnology to transit safely from bench to bedside.
Assuntos
Cádmio/toxicidade , Poluentes Ambientais/toxicidade , Nanopartículas Metálicas , Nanotecnologia , Pontos Quânticos , Animais , Cádmio/farmacocinética , Cádmio/uso terapêutico , Diagnóstico por Imagem/efeitos adversos , Relação Dose-Resposta a Droga , Humanos , Neoplasias/induzido quimicamente , Tamanho da Partícula , Medição de RiscoAssuntos
Suplementos Nutricionais/efeitos adversos , Neoplasias da Próstata/induzido quimicamente , Zinco/efeitos adversos , Adulto , Idoso , Cádmio/efeitos adversos , Cádmio/uso terapêutico , Carcinógenos/toxicidade , Suplementos Nutricionais/estatística & dados numéricos , Contaminação de Medicamentos , Humanos , Masculino , Nova Zelândia/epidemiologia , Neoplasias da Próstata/epidemiologia , Zinco/uso terapêuticoRESUMO
Cadmium is known to be a potent carcinogenic and mutagenic metal. However, we demonstrated that dietary supplementation with 50 ppm cadmium inhibits spontaneous carcinogenesis in C3H/HeN and spontaneous hepatitis in A/J mice. We found that the frequencies of spontaneous hepatocarcinogenesis in C3H/HeN mice and of spontaneous hepatitis in A/J mice fed low-dose cadmium for 54 weeks were significantly lower than those in the respective control groups. A cadmium-induced increase in metallothionein production itself and/or metallothionein-associated increases in hepatic zinc concentrations may be involved in the observed preventive effects of cadmium. Our results suggest that low doses of cadmium in the diet or environment may play a beneficial role in the prevention of hepatic disease in humans and animals.
Assuntos
Cádmio/uso terapêutico , Dieta , Neoplasias Hepáticas Experimentais/prevenção & controle , Animais , Cádmio/administração & dosagem , Relação Dose-Resposta a Droga , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas Experimentais/patologia , Masculino , Metalotioneína/biossíntese , Camundongos , Camundongos Endogâmicos C57BL , Especificidade da Espécie , Zinco/metabolismoRESUMO
PURPOSE: Response of quiescent (Q) and total tumor cells in solid tumors to reactor neutron beam irradiation with two different cadmium (Cd) ratios was examined in terms of micronucleus (MN) frequency and apoptosis frequency, using four different tumor cell lines. METHODS AND MATERIALS: C57BL mice bearing EL4 tumors, C3H/He mice bearing SCC VII or FM3A tumors, and Balb/c mice bearing EMT6/KU tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty min after i.p. injection of sodium borocaptate-10B (BSH), or 3 h after oral administration of p-boronophenylalanine-10B (BPA), the tumors were irradiated with neutron beams. The tumors without 10B-compound administration were irradiated with neutron beams or gamma-rays. This neutron beam irradiation was performed using neutrons with two different Cd ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the MN frequency in cells without BrdU labeling (=Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, for apoptosis assay, 6 h after irradiation, tumor cell suspensions obtained in the same manner were fixed, and the apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequencies in total (P + Q) tumor cells were determined from the tumors that were not pretreated with BrdU. RESULTS: Without 10B-compounds, the sensitivity difference between total and Q cells was reduced by neutron beam irradiation. Under our particular neutron beam irradiation condition, relative biological effectiveness (RBE) of neutrons was larger in Q cells than in total cells, and the RBE values were larger for low Cd-ratio than high Cd-ratio neutrons. With 10B-compounds, both frequencies were increased for each cell population, especially for total cells. BPA increased both frequencies for total cells more than BSH did. Nevertheless, the sensitivity of Q cells treated with BPA was lower than that of Q cells treated with BSH. Whether based on the MN frequency or the apoptosis frequency, similar results concerning the sensitivity difference between total and Q cells, the values of RBE, and the enhancement effect by the use of 10B-compound were obtained. CONCLUSION: Apoptosis frequency, as well as the MN frequency, can be applied to our method for measuring the Q cell response to reactor neutron beam irradiation within solid tumor in which the ratio of apoptosis to total cell death is relatively high, as in EL4 tumor. The absolute radiation dose required to achieve the same endpoint for Q cells is much higher than that for total cells when combined with 10B-compound, especially with BPA.
Assuntos
Apoptose , Terapia por Captura de Nêutron de Boro/métodos , Cádmio/uso terapêutico , Neoplasias/radioterapia , Nêutrons/uso terapêutico , Fenilalanina/análogos & derivados , Radiossensibilizantes/uso terapêutico , Radioisótopos/uso terapêutico , Animais , Boroidretos/uso terapêutico , Compostos de Boro/uso terapêutico , Bromodesoxiuridina , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Citocalasina B/farmacologia , Imunofluorescência , Linfoma/patologia , Linfoma/radioterapia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Testes para Micronúcleos , Neoplasias/patologia , Fenilalanina/uso terapêutico , Tolerância a Radiação , Radiobiologia , Eficiência Biológica Relativa , Sarcoma Experimental/patologia , Sarcoma Experimental/radioterapia , Compostos de Sulfidrila/uso terapêutico , Células Tumorais Cultivadas/efeitos da radiaçãoRESUMO
Previously, we found that oral cadmium (Cd) treatment either prevented or substantially reduced N-nitrosodiethylamine (NDEA)-induced tumor formation in B6C3F1 mouse liver or lung regardless of exposure interval and even when the Cd was given well after tumors were formed. Because Cd salts are powerful emetics, oral exposure would probably be impractical in humans. Thus, we studied suppression of NDEA-initiated tumors in male B6C3F1 mice by a single i.v. dose of Cd. NDEA (776 mumol/kg i.p.) was given at time 0 followed by CdCl2 (16 mumol/kg i.v.) 40 weeks later. This dose of Cd had no effect on body weights through the conclusion of the study at 52 weeks. The NDEA-induced increase in hepatic tumor incidence (19 tumor-bearing mice/22 mice at risk, 86%) over control (5/24, 21%) was remarkably reduced by Cd treatment (13/27, 48%, P < or = .05). Multiplicity and size of liver tumors induced by NDEA (2.18 tumors/liver; 31.6 mm3 mean volume) were also substantially reduced by the Cd exposure (0.96 tumors/liver; 17.1 mm3 mean volume). NDEA-induced lung tumor incidence (22/22, 100%) and multiplicity (5.09 tumors/lung) were modestly, but significantly, reduced by Cd treatment (21/27, 78%; 3.89 tumors/lung). Clear evidence of tumor-specific cytotoxicity was observed as Cd treatment induced a necrotizing effect that was localized only within the hepatic tumors. Metallothionein (MT), an inducible metal-binding protein associated with tolerance to many metal including Cd, was not detected immunohistochemically in mouse liver tumors, even those undergoing Cd-induced necrosis, whereas the surrounding normal liver cells expressed high levels of MT after Cd exposure. Likewise, in human hepatocellular carcinomas MT was only poorly or erratically expressed relative to normal tissue. These results indicate that a single, nontoxic dose of Cd dramatically reduces liver tumor burden through tumor cell-specific necrosis due to a down-regulation of MT expression in hepatic tumors of murine origin and furthermore indicate that a similar down-regulation of MT occurs in human hepatocellular carcinomas.
Assuntos
Antineoplásicos/farmacologia , Cádmio/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Metalotioneína/análise , Animais , Cádmio/uso terapêutico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Dietilnitrosamina , Regulação para Baixo , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Metalotioneína/genética , Camundongos , Necrose , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
BACKGROUND: The combination of VP-16 and cisplatin is one of the most active regimens available for the treatment of small cell lung cancer (SCLC), however, most tumors eventually become resistant to these drugs. METHODS: To investigate the problem of resistance to VP-16 and cisplatin in patients with SCLC, we established two resistant sublines from the drug sensitive human SCLC line, NCI-H209, by in vitro selection in VP-16 and cisplatin. RESULTS: The VP-16-selected cell line, H209/VP, was more than 100-fold resistant to VP-16, and displayed cross-resistance to VM-26 and other topoisomerase II interactive drugs, but not to vinca alkaloids. There was no difference in accumulation of VP-16 in H209/VP compared with its parent cell line. The level of topoisomerase II-alpha was reduced to 8% of that in the parent cell line, and there was an altered form of this enzyme with a molecular weight of 160 kilodaltons (kDa), in addition to the normal 170 kDa protein. The cisplatin-selected cell line, H209/CP, was 11.5-fold resistant to cisplatin, with only a low level of cross-resistance to other platinum compounds including carboplatin, tetraplatin, iproplatin, and lobaplatin. This line was highly cross-resistant to vinca alkaloids, but not to anthracyclines or epipodophyllotoxins. The H209/CP cell line was not resistant to cadium chloride, suggesting that alterations in metallothionein are unlikely to be a cause of resistance. Although glutathione (GSH) levels were increased nearly 2-fold in H209/CP, there was no difference in levels of the GSH-related enzymes glutathione-S-transferase, glutathione peroxidase, and glutathione reductase, compared with the parent line. The H209/CP line had a 1.4-fold elevation of topoisomerase II-alpha. The accumulation of cisplatin was reduced in this cell line, and there were fewer DNA-interstrand cross links formed in the presence of cisplatin in H209/CP, compared with the parent line. Neither H209/VP nor H209/CP expressed MDR1, the gene for P-glycoprotein. The MRP gene was expressed at a slightly higher level in the H209/VP cell line, but there was no significant increase in expression of this gene in the H209/CP cell line. CONCLUSIONS: The resistance of the H209/VP cell line is associated with an alteration of topoisomerase II-alpha, whereas the resistance in the H209/CP line is associated with reduced drug accumulation.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Cisplatino/uso terapêutico , Etoposídeo/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Cádmio/farmacologia , Cádmio/uso terapêutico , Cloreto de Cádmio , Carcinoma de Células Pequenas/enzimologia , Carcinoma de Células Pequenas/fisiopatologia , Linhagem Celular , Cloretos/farmacologia , Cloretos/uso terapêutico , Cisplatino/farmacologia , Reações Cruzadas , DNA/efeitos dos fármacos , DNA Topoisomerases Tipo II/análise , DNA Topoisomerases Tipo II/farmacologia , DNA Topoisomerases Tipo II/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/fisiologia , Etoposídeo/farmacologia , Regulação Neoplásica da Expressão Gênica , Glutationa/análise , Glutationa Peroxidase/análise , Glutationa Redutase/análise , Glutationa Transferase/análise , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/fisiopatologia , Metalotioneína/metabolismo , Compostos de Platina/farmacologia , Compostos de Platina/uso terapêutico , Podofilotoxina/farmacologia , Podofilotoxina/uso terapêutico , Teniposídeo/farmacologia , Teniposídeo/uso terapêutico , Células Tumorais Cultivadas , Alcaloides de Vinca/farmacologia , Alcaloides de Vinca/uso terapêuticoRESUMO
Previously, we studied the ability of cadmium to initiate or promote tumors in B6C3F1 mice and, contrary to expectation, found that cadmium inhibited development of N-nitrosodiethylamine (NDEA)-initiated and sodium barbital-promoted liver tumors. In this study, the time course of cadmium inhibition of NDEA-initiated tumor formation was studied. A single dose of NDEA (90 mg/kg i.p.) was given at 5 weeks of age (time 0) followed by cadmium (1000 ppm) in drinking water from 2 to 48, 4 to 48, 8 to 48, 16 to 48 and 32 to 48 weeks. The study ended at 48 weeks. NDEA-induced elevations in liver tumor incidence (22 tumor-bearing mice/25 total) over control (5/25) were prevented by cadmium regardless of the period of administration (NDEA + cadmium: 2-48 weeks, 2/25; 4-48 weeks, 1/25; 8-48 weeks, 1/25; 16-48 weeks, 2/25; 32-48 weeks, 6/24). Cadmium alone (2-48 weeks) eliminated (0/25) spontaneously occurring liver tumors (5/25). NDEA-induced lung tumor incidence (25/25) and multiplicity (7.28 tumors/lung) were also reduced by cadmium (maximal decreases 28% and 80%, respectively). Some evidence of a specific deficiency of metallothionein in tumor cells was seen immunohistologically in NDEA-induced hepatic lesions and pulmonary lesions. These results indicate that cadmium prevents or reduces tumor formation in the B6C3F1 mouse liver and lung regardless of the exposure interval and apparently by cell-specific cytotoxicity. Auxiliary studies indicated that in mice bearing multiple liver foci resulting from NDEA treatment there was a marked reduction in basal metallothionein levels and in response to zinc induction.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Anticarcinógenos/uso terapêutico , Cádmio/uso terapêutico , Neoplasias Hepáticas Experimentais/prevenção & controle , Neoplasias Pulmonares/prevenção & controle , Metalotioneína/fisiologia , Animais , Peso Corporal/efeitos dos fármacos , Dietilnitrosamina , Fígado/química , Fígado/efeitos dos fármacos , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/química , Pulmão/efeitos dos fármacos , Neoplasias Pulmonares/induzido quimicamente , Masculino , Metalotioneína/análise , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos , Fatores de TempoRESUMO
Campylobacter jejuni (10(8) C.F.U) fed intragastrically unto 18 laboratory rats (white whiskers) resulted in colonization of the 18 rats intestines and their eventual excretion of the organism for four months post infection. When 10(8) CFU of C. jejuni was mixed with 10 mu/ml of cadmium chloride (CdCl2) and fed immediately to another set of 18 rats, colonization of rats intestines was greatly reduced and C. jejuni was recovered from two (11%) out of 18 rats and the faeces were positive for C. jejuni for a maximum of 29 days. Six control rats given 1 ml of phosphate buffered saline (PBS) and a second set of another six control animals given 1 ml of PBS containing 10 micrograms/ml of CdCl2 gave negative result for C. jejuni throughout the experiment. This work depicts an in vivo effect of CdCl2 on C. jejuni and may be of importance in the control of C. jejuni colonization in experimental animals.
Assuntos
Cádmio/uso terapêutico , Infecções por Campylobacter/tratamento farmacológico , Campylobacter jejuni , Cloretos/uso terapêutico , Enteropatias/tratamento farmacológico , Administração Oral , Animais , Aderência Bacteriana , Cádmio/administração & dosagem , Cádmio/farmacologia , Cloreto de Cádmio , Infecções por Campylobacter/microbiologia , Cloretos/administração & dosagem , Cloretos/farmacologia , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Fezes/microbiologia , Enteropatias/microbiologia , RatosRESUMO
One group of male Wistar rats (Group B) was pretreated by a daily subcutaneous injection with CdCl2 during 5 days with increasing doses (0.5, 1, 1, 2 and 2 mg Cd/kg). Another group of rats (Group A) was daily given normal saline subcutaneously for 5 days. On the second day after the last injection, a single s.c. injection of 109Cd-metallothionein (CdMT, 0.4 mg Cd/kg) was given to each animal in both groups. Urinary calcium, protein, metallothionein (MT), N-acetyl-beta-D-glucosaminidase (NAG) and gamma glutamyltransferase (gamma-GT) were measured. In Group A, calciuria, proteinuria, metallothioneinuria and enzymuria was induced by CdMT. Calciuria reached a peak during 0-6 h after the administration of CdMT, thus appearing earlier than other effects. Enzymuria was displayed at 6-12 h for gamma-GT and 12-24 h for NAG. A prominent increase of proteinuria appeared at 24-48 h after the challenge of CdMT. In Group B, no significant increase of urinary calcium, protein, or NAG was observed after the CdMT injection and urinary gamma-GT was only slightly elevated, thus demonstrating the protective action of pretreatment. This study demonstrates for the first time that calciuria, one of the signs of cadmium nephrotoxicity, can be prevented by cadmium pretreatment. Urinary MT increased slightly during the 4-5 days of CdCl2 pretreatment. This is in accordance with previous observations that cadmium pretreatment induces new synthesis of MT which is likely to constitute the background for the resistance to the CdMT challenge to the kidney.
Assuntos
Cádmio/uso terapêutico , Cálcio/urina , Cloretos/uso terapêutico , Nefropatias/prevenção & controle , Metalotioneína/toxicidade , Acetilglucosaminidase/urina , Animais , Cloreto de Cádmio , Nefropatias/induzido quimicamente , Nefropatias/urina , Túbulos Renais/efeitos dos fármacos , Masculino , Metalotioneína/urina , Néfrons/efeitos dos fármacos , Proteinúria/induzido quimicamente , Ratos , Ratos Wistar , Fatores de Tempo , gama-Glutamiltransferase/urinaRESUMO
The B6C3F1 mouse liver has been widely used for the evaluation of carcinogenic or tumor promoting efficacy of various organic compounds, although little is known about the actions of metallic carcinogens in this system. Thus, the ability of cadmium to initiate or promote tumors in B6C3F1 mouse liver was studied. In promotion studies, diethylnitrosamine (DEN; 90 mg/kg, ip) was given as an initiator to 5-week-old mice followed 2 weeks later by 500 or 1000 ppm of cadmium in drinking water for 50 weeks. DEN caused an elevation of liver tumor incidence (13 tumor bearing mice/45 total) over control (1/48) which was prevented by cadmium (DEN + 500 ppm cadmium, 3/42; DEN + 1000 cadmium, 0/47). Cadmium alone did not further reduce the very low spontaneous liver and lung tumor incidence at approximately 1 year of age. DEN-induced lung tumor incidence (15/45) was also reduced by cadmium (DEN + 500 ppm cadmium, 11/42; DEN + 1000 ppm cadmium, 1/47) to control levels (0/48). In initiation studies, cadmium (20 or 22.5 mumol/kg, sc) was given to 5-week-old mice (n = 30-60) 2 weeks before an established promoting regimen of sodium barbital (BB) in drinking water at 500 ppm level was begun. Barbital in drinking water was given continuously for up to 92 weeks. Such cadmium doses caused acute, focal hepatic necrosis. Mice treated with BB and killed at 97 weeks of age showed an elevation of liver tumor multiplicity (7.44 tumors/liver) over control (2.24) that was prevented by cadmium in a dose-related manner (20 mumol/kg cadmium + BB, 3.93; 22.5 mumol/kg cadmium + BB, 1.87). Cadmium alone given by injection also reduced spontaneous liver tumor multiplicity. These results indicate that cadmium inhibits tumor formation in the B6C3F1 mouse liver initiation/promotion system regardless of route of exposure or sequence of administration. The possibility exists that cadmium has a specific toxicity toward previously initiated cells within liver and lung.
Assuntos
Antineoplásicos , Cádmio/uso terapêutico , Neoplasias Hepáticas/prevenção & controle , Neoplasias Pulmonares/prevenção & controle , Administração Oral , Animais , Barbital/farmacologia , Cádmio/administração & dosagem , Cloreto de Cádmio , Dietilnitrosamina , Relação Dose-Resposta a Droga , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Pulmonares/induzido quimicamente , Masculino , Camundongos , Camundongos EndogâmicosRESUMO
Three murine sarcoma cells (Dunn osteosarcoma, Gunma clone-4, Sarcoma 1509a) were cultured for four days at various concentrations of CdCl2 or ZnCl2 and assayed for their viability. Dunn osteosarcoma was more sensitive to CdCl2 and less sensitive to ZnCl2 than the others. CdCl2 and ZnCl2 were weekly administered to C3H/He mice intraperitoneally from three days after the inoculation of Dunn osteosarcoma. The size of the tumors was measured twice a week for five weeks. CdCl2 suppressed the growth of the tumor, whereas ZnCl2 did not. These results suggest that CdCl2 has antitumor activity, especially against osteosarcoma.
Assuntos
Antineoplásicos , Cádmio/farmacologia , Cloretos/farmacologia , Osteossarcoma/patologia , Compostos de Zinco , Zinco/farmacologia , Animais , Antineoplásicos/uso terapêutico , Cádmio/uso terapêutico , Cloreto de Cádmio , Sobrevivência Celular/efeitos dos fármacos , Cloretos/uso terapêutico , Ensaios de Seleção de Medicamentos Antitumorais , Camundongos , Camundongos Endogâmicos C3H , Transplante de Neoplasias , Osteossarcoma/tratamento farmacológico , Sarcoma Experimental/patologia , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/patologia , Zinco/uso terapêuticoRESUMO
Subpopulations of human tumor-derived cell lines A101D, A204, and A549 were screened for Cd2+ cytotoxic response. Three of six A549, two of seven A101D, and four of seven A204 subpopulations were found to differ significantly from the parental line. A variant subpopulation of A101D (T3) was shown by flow cytometry to be comprised of cells having two distinct DNA histograms. One histogram, type 1, resembles that of normal human fibroblasts. The other, type 2, represents cells with one-third more DNA. Early passage T3 clonal populations were comprised primarily of type 1 cells. With passage, type 1 cells decreased relative to type 2 so that by passage 47 the culture was predominantly type 2. Correspondingly, the A101D T3 subpopulation became more Cd2+ sensitive with time in culture. Subclones having only type 1 DNA histograms were found to be Cd2+ resistant relative to subclones with type 2 histograms, and treatment of A101D T3 cultures having approximately equal amounts of type 1 and 2 cells with 2 microM Cd2+ resulted in the selection of type 1 cells. The enhanced Cd2+ resistance phenotype shown by A101D T3 type 1 cells correlated with reduced Cd2+ uptake and is not attributable to enhanced metallothionein synthesis.
Assuntos
Antineoplásicos/uso terapêutico , Cádmio/uso terapêutico , Variação Genética , Neoplasias/genética , Análise de Variância , Cádmio/metabolismo , Linhagem Celular , Células Clonais , DNA de Neoplasias/metabolismo , Resistência a Medicamentos , Humanos , Metalotioneína/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologiaRESUMO
The aim of this investigation was to establish the relationship of cadmium-induced fetal growth retardation in the mouse to iron deficiency. Pregnant mice were either fed a low iron diet or given 40 ppm cadmium in their drinking water. The effects of these factors on fetal weight and hematological values of the fetuses and dams were established and compared, both with each other and with appropriate controls. Both treatments caused maternal and fetal anemia, the fetuses being more severely affected. The anemic fetuses were also severely growth retarded. These changes, when caused by the iron deficient diet, could be completely prevented by either parenterally or orally administered iron supplements. When the changes were caused by cadmium in the drinking water they were only partially prevented by oral supplements. From these results it was concluded that iron deficiency in pregnancy causes not only anemia but also fetal growth retardation. Cadmium exposure in pregnancy, presumably by blocking intestinal absorption of iron, also causes anemia and hence fetal growth retardation.