RESUMO
Cadmium (Cd) is associated with non-alcoholic fatty liver disease (NAFLD). The hepatic activation of p53/miR-43a-induced suppression of SIRT1/FXR axis plays a significant role in the development of NAFLD. In this study, we have investigated CdCl2-induced NAFLD in rats involves activation of miR34a/SIRT1/FXR axis. Adult male rats were divided into 4 groups (n-8/each) as a control, CdCl2 (10 mg/l), CdCl2 + miR-34a antagomir (inhibitor), and CdCl2 + SRT1720 (a SIRT1 activator) for 8 weeks, daily. With no effect on fasting glucose and insulin levels, CdCl2 significantly reduced rats' final body, fat pads, and liver weights, and food intake. Concomitantly, it increased the circulatory levels of liver markers (ALT, AST, and γ-GTT), increased the serum and hepatic levels of total cholesterol and triglycerides coincided with increased hepatic lipid accumulation. Besides, it increased the mRNA and protein levels of SREBP1, SREBP2, FAS, and HMGCOA reductase but reduced mRNA levels of PPARα, CPT1, and CPT2. Interestingly, CdCl2 also increased mRNA levels of miR34 without altering mRNA levels of SIRT1 but with a significant reduction in protein levels of SIRT1. These effects were associated with increased total protein levels of p53 and acetylated protein of p53, and FXR. Of note, suppressing miR-34a with a specific anatomic or activating SIRT1 by SRT1720 completely prevented all these effects and reduced hepatic fat accumulations in the livers of rats. In conclusion, CdCl2 induced NAFLD by increasing the transcription of miR-34a which in turn downregulates SIRT1 at the translational level.
Assuntos
Cloreto de Cádmio/efeitos adversos , MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Animais , Fígado/metabolismo , Masculino , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Proteínas de Ligação a RNA , Ratos , Sirtuína 1/genética , Sirtuína 1/metabolismo , Proteína Supressora de Tumor p53RESUMO
Proton pumps are membrane-bound enzymes important in generating gradients that help in maintaining cellular ion homeostasis, cell membrane potential, water, and solute transport across the cell surface. This study investigated the modulatory role of vitamin E on proton pump activity and reproductive parameters in cadmium-induced testicular damage. Twenty (20) male Wistar rats weighing between 180 and 200 g were sorted into 4 groups of five rats each. Group I served as the control and was given normal saline orally, Group II rats were treated with a single dose of 2 mg/kg BW cadmium chloride (CdCl2) intraperitoneally, Group III rats were given 100 mg/kg BW of vitamin E orally, and Group IV rats were given 100 mg/kg BW of vitamin E orally for 30 days prior to intraperitoneal administration of single dose of 2 mg/kg BW of cadmium chloride. The rats were anaesthetized with diethyl ether, and blood samples were obtained for sex hormonal analysis; caudal epididymis was dissected for sperm count, motility, and viability, and the testis were homogenized for lipid peroxidation and proton pump (Na+/K+ ATPase, Ca2+ ATPase, and Mg2+ ATPase) activity. Proton pump activity was assayed spectrophotometrically using the Stewart method to determine the inorganic phosphate level. Histopathological changes of the testis were also studied. The group treated with CdCl2 showed a significant (p < 0.05) decrease in proton pump activity, sperm count, and motility and a significant (p < 0.05) increase in malondialdehyde level when compared with the control group. The CdCl2-treated group also showed decrease reproductive organ weights and hormonal levels and cause necrosis of spermatogonia lining the seminiferous tubules. Rats treated with vitamin E orally for 30 days prior to CdCl2 exposure showed improvement in proton pump activity, a significant (p < 0.05) increase in sperm parameters and luteinizing hormonal level, and a decrease in the lipid peroxidation level as compared with the CdCl2 group. This study showed that vitamin E ameliorated the toxic effect of CdCl2 on proton pump activity in the testes, hence improving testicular integrity, structures, and functions.
Assuntos
Adenosina Trifosfatases , Cloreto de Cádmio/efeitos adversos , Bombas de Próton , Testículo , Vitamina E/farmacologia , Adenosina Trifosfatases/efeitos dos fármacos , Adenosina Trifosfatases/metabolismo , Animais , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Bombas de Próton/efeitos dos fármacos , Bombas de Próton/metabolismo , Ratos , Ratos Wistar , Doenças Testiculares/induzido quimicamente , Doenças Testiculares/metabolismo , Testículo/efeitos dos fármacos , Testículo/enzimologia , Testículo/metabolismo , Testículo/patologiaRESUMO
AIM AND OBJECTIVE: Cells and tissues of the body are prone to oxidative damage as a result of an increased level of reactive oxygen species and nitrogen radical beyond the detoxifying ability of the endogenous antioxidant system. This study aimed to evaluate the ameliorative effect of methanolic extracts of Nigella sativa (MENS) against cadmium-induced blood oxidative stress and testicular toxicity in albino rats. MATERIALS AND METHODS: Twenty-five (25) male albino rats, weighing (200 ± 20g), were randomly grouped into five groups (A-E). Group B (Negative Control) received intraperitoneal administration of cadmium chloride (CdCl2, 5 mg/kg) only, group C received CdCl2 and low dose MENS (300 mg/kg, oral), group D received CdCl2 and high dose MENS (600 mg/kg, oral), group E (Positive control) received CdCl2 and Vitamin C (200 mg/kg, oral), for 14 days. No treatment was administered to group A (Normal control). The oxidative state of the blood was assessed by measuring the blood levels or activities of MDA, CAT, GSH and SOD; while testicular injury was assessed by measuring serum testosterone level using ELISA. The testes were harvested for histopathological examination. RESULTS: The results showed that cadmium induced a marked elevation in the level of MDA, and a decrease in SOD, CAT and GSH levels or activities (p<0.05 or p<0.01); but no significant alteration in the serum testosterone level was found (p>0.05); Histopathological studies on the testes showed that cadmium significantly induced testicular injury, which was however ameliorated by the seed extract of N. sativa. CONCLUSION: We conclude that N. sativa seed extract is potentially testiculoprotective and attenuates oxidative stress against harmful chemical toxins such as cadmium.
Assuntos
Antioxidantes/metabolismo , Cloreto de Cádmio/efeitos adversos , Nigella sativa/química , Oxidantes/metabolismo , Extratos Vegetais/química , Substâncias Protetoras/química , Sementes/química , Alcaloides/química , Animais , Antioxidantes/análise , Antioxidantes/farmacologia , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/metabolismo , Cloreto de Cádmio/administração & dosagem , Relação Dose-Resposta a Droga , Descoberta de Drogas , Flavonoides/química , Humanos , Masculino , Modelos Animais , Oxidantes/sangue , Oxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Ratos , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Testículo/metabolismoRESUMO
The objective of the present study is to identify the possible regulatory role of trehalose (Tre) against cadmium chloride (CdCl2 )-induced endothelial cell dysfunction. To screen the dose-dependent effect of both Tre and CdCl2 , a methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was performed. Interestingly, MTT assay results have shown that co-incubation of Tre (1 mM) with CdCl2 significantly decreased the CdCl2 (5 µM) cytotoxicity. Nitric oxide (NO) measurement using Griess assay and 4-amino-5-methylamino-2',7'-difluorofluorescein fluorescence probe results have shown that CdCl2 decreases NO production in endothelial cells. Western blotting analysis results showed that CdCl2 decreases endothelial nitric oxide synthase (eNOS) and phospho endothelial nitric oxide synthase (peNOS) expression. The present study results have also observed that CdCl2 treatment increases reactive oxygen species (ROS) production. However, combination treatment (Tre + CdCl2 ) could restore the NO production in CdCl2 -treated cells. In addition, combination treatment could also restore eNOS and peNOS expression in endothelial cells. Moreover, Tre treatment was found to decrease CdCl2 -induced ROS production. Collectively, the present study results demonstrate that Tre possesses a significant protective action against CdCl2 -mediated endothelial dysfunction by increasing NO production, eNOS and peNOS expression, and by decreasing oxidative stress.
Assuntos
Células Endoteliais/efeitos dos fármacos , Trealose/metabolismo , Trealose/farmacologia , Cloreto de Cádmio/efeitos adversos , Cloreto de Cádmio/metabolismo , Cloreto de Cádmio/farmacologia , Células Cultivadas , Células Endoteliais/metabolismo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Chemical contaminants such as industrial and urban by-products, pharmaceuticals, drugs metabolites and, plastics, are continuously found in the oceans, affecting its quality and organism's welfare. Although these compounds are found at concentrations ranged ng L-1, there is an increasing concern about the potential adverse effects of the interactions among those substances present, simultaneously, in a mixture. In the present study, specimens of sea bream (Sparus aurata) were exposed, by food, to rising concentrations of a mixture of carbamazepine, polybrominated diphenyl ether-47 and cadmium chloride, for 15 days and then, maintained, with the same control diet, without contaminants, for other 15 days. Samples of skin mucus, serum, head-kidney, liver and intestine were sampled at 0, 15 and 30 days. Cellular immune parameters were evaluated on head-kidney, as well as humoral parameters were determined on skin mucus and serum. In addition, the expression of some genes, related to immunity, was analysed on liver and intestine. Both cellular and humoral response were affected at 15 days, showing slightly signs of recovery at 30 days. Besides, the expression of immune-related genes was highly affected, suggesting the development of inflammatory processes, as well as a reduction of immune parameters. Overall, the mixture of compounds severally affected the immune system of sea bream, suggesting a lower degree of recovery. The prolonged exposure to a mixture of these compounds could entail serious change on population immunity and, eventually, promote changes on marine biota.
Assuntos
Doenças dos Peixes/imunologia , Imunidade Celular , Imunidade Humoral , Inflamação/veterinária , Dourada/imunologia , Poluentes Químicos da Água/efeitos adversos , Animais , Cloreto de Cádmio/efeitos adversos , Carbamazepina/efeitos adversos , Doenças dos Peixes/induzido quimicamente , Éteres Difenil Halogenados/efeitos adversos , Inflamação/induzido quimicamente , Inflamação/imunologiaRESUMO
Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, plays an important regulatory role in the activation of T cells induced by mitogenic or antigenic stimuli. However, the immunologic property of MIF in freshwater fish is limitedly known by now. In the present study, MIF gene was identified in grass carp. Bioinformatics analysis revealed that the molecular weight of grass carp MIF protein was 12.377 kDa and it could also bind to CD74. MIF gene was predominantly expressed in immune tissues including spleen and head kidney, then liver, skin, gill, intestine and blood, while a relative low level expression in heart, brain, fat and red muscle. The predicted receptor and tissues distribution of MIF implied the immunologic activity of grass carp MIF. Then grass carp MIF antigen and the polyclonal antibodies against it were prepared. Using cadmium as an immunosuppressive agent, MIF expression in spleen and head kidney was depressed in a dose-dependent manner with cadmium consumption. On the same time, white blood cell count decrease displayed a similar pattern with MIF expression, which suggested a possible positive correlation between MIF and white blood cell count. Thereafter, MIF enhanced the viability of grass carp peripheral blood leukocytes and inhibited cell apoptosis with depressed reactive oxygen species production in vitro. In addition, recombinant grass carp MIF promoted tumor necrosis factor-alpha (TNF-α), interleukin 1ß (IL1ß) and interleukin 6 (IL6) secretion from peripheral blood leukocytes. These results indicated the immunologic property of grass carp MIF.
Assuntos
Cloreto de Cádmio/efeitos adversos , Carpas/genética , Carpas/imunologia , Fatores Inibidores da Migração de Macrófagos/genética , Fatores Inibidores da Migração de Macrófagos/imunologia , Poluentes Químicos da Água/efeitos adversos , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Leucócitos/imunologia , Fases de Leitura Aberta , Distribuição AleatóriaRESUMO
AIMS: Cadmium chloride has various industrial applications and considered an industrial and environmental pollutant. The aim of this study was to evaluate the effect of atorvastatin on Cadmium chloride-induced hepatotoxicity in male rats. MATERIALS AND METHODS: Fifty-six adult male rats, randomly were divided into 8 groups. Groups 1-3 were received atorvastatin (20 mg/kg) intragastrically for 15 days during which Cadmium chloride (1, 2, and 3 mg/kg) were given intraperitoneally from days 8 to 15. Groups 4-6 were as first three groups but animals were received vehicle of atorvastatin. Group 7 was received vehicle of atorvastatin and vehicle of Cadmium chloride and Group 8 was received atorvastatin and vehicle of Cadmium chloride according to timeline of other groups. On day 16, under full anesthesia, blood sampling was prepared from heart, and livers were dissected out to analyses the biochemical and histopathology studies. KEY FINDINGS: Cadmium chloride significantly increased aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) in the serum. Malondialdehyde (MDA) significantly increased and superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione (GSH) significantly decreased the in the liver following Cadmium chloride administration. Atorvastatin significantly improved the levels of MDA, SOD, GPx, GSH, but not ALT, AST, and ALP in Cadmium chloride-treated rats. In histopathological studies, atorvastatin could not improve injured liver tissues induced by Cadmium chloride. SIGNIFICANCE: Atorvastatin has beneficial effects in improving Cadmium chloride-induced antioxidative enzymes disturbance which may be contribute to improving liver function in male rats.
Assuntos
Atorvastatina/farmacologia , Alanina Transaminase/sangue , Fosfatase Alcalina/metabolismo , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/sangue , Atorvastatina/metabolismo , Cádmio/toxicidade , Cloreto de Cádmio/efeitos adversos , Cloreto de Cádmio/farmacologia , Cloreto de Cádmio/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
Cadmium is an environmental contaminant that can activate estrogen receptor alpha (ERα) and contribute to the development and progression of breast cancer. Our lab previously demonstrated that chronic cadmium exposure alters the expression of several ERα-responsive genes and increases the malignancy of breast cancer cells. Although these studies support cadmium's function as a hormone disrupter, the role of ERα in cadmium-induced breast cancer progression remains unclear. To address this, we modulated the expression of ERα and found that while the loss of ERα significantly impaired cancer cell growth, migration, invasion and anchorage-independent growth in both MCF7 and MCF7-Cd cells, cadmium-exposed cells retained a significant advantage in cell growth, migration, and invasion, and partially circumvented the loss of ERα. ERα knockout in MCF7 and MCF7-Cd cells significantly reduced the expression of classical ERα-regulated genes, while non-classical ERα-regulated genes were less impacted by the loss of ERα in MCF7-Cd cells. This is the first study to show that chronic cadmium exposure, even at low levels, can increase the malignancy of breast cancer cells by decreasing their dependency on ERα and increasing the adaptability of the cancer cells.
Assuntos
Adenocarcinoma/metabolismo , Neoplasias da Mama/metabolismo , Cloreto de Cádmio/efeitos adversos , Receptor alfa de Estrogênio/metabolismo , Adenocarcinoma/genética , Neoplasias da Mama/genética , Sistemas CRISPR-Cas , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Receptor alfa de Estrogênio/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Células MCF-7 , Invasividade Neoplásica/fisiopatologiaRESUMO
Metals and heavy metals are natural contaminants with an increasing presence in aquatic ecosystems as a result of human activities. Although they are mixed in the water, research is usually focused on analyzing them in isolation, so there is a lack of knowledge about their combined effects. The aim of this work was to assess the damage produced by mixtures of cadmium and copper, two frequent metals used in industry, in the harlequin midge Chironomus riparius (Diptera). The effects of acute doses of cadmium and copper were evaluated in fourth instar larvae by analyzing the mRNA levels of six genes related to apoptosis (DRONC, IAP1), immune system (PO1, Defensin), stress (Gp93), and copper homeostasis (Ctr1). DRONC, Ctr1, and IAP1 transcripts are described here for first time in this species. Individual fourth instar larvae were submitted to 10⯵M, 1⯵M and 0.1⯵M of CdCl2 or CuCl2, and mixture. The employed individuals came from different egg masses. Real-time PCR analysis showed a complex pattern of alterations in transcriptional activity for two genes, DRONC and Gp93, while the rest of them did not show any statistically significant differences. The effector caspase DRONC showed upregulation with the highest concentration tested of the mixture. In case of gp93, chaperone involved in regulation of immune response, differences in expression levels were found with 1 and 10⯵M Cu and 0.1 and 10⯵M of mixtures, compared to control samples. These results suggest that mixtures affect the transcriptional activity differently and produce changes in apoptosis and stress processes, although it is also possible that Gp93 alteration could be related to the immune system since it is homologous to human protein Gp96, which has been related with Toll-like receptors. In conclusion, cadmium and copper mixtures can affect the population by affecting the ability of larvae to respond to the infection and the apoptosis, an important process in the metamorphosis of insects.
Assuntos
Apoptose/efeitos dos fármacos , Cloreto de Cádmio/efeitos adversos , Chironomidae/efeitos dos fármacos , Cobre/efeitos adversos , Proteínas de Insetos/genética , Transcrição Gênica/efeitos dos fármacos , Poluentes Químicos da Água/efeitos adversos , Animais , Apoptose/genética , Chironomidae/genética , Chironomidae/crescimento & desenvolvimento , Chironomidae/fisiologia , Relação Dose-Resposta a Droga , Proteínas de Insetos/metabolismo , Larva/efeitos dos fármacos , Larva/fisiologia , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Regulação para CimaRESUMO
Pollution-induced skin damage results in oxidative stress; cellular toxicity; inflammation; and, ultimately, premature skin aging. Previous studies suggest that the activation of autophagy can protect oxidation-induced cellular damage and aging-like changes in skin. In order to develop new anti-pollution ingredients, this study screened various kinds of natural extracts to measure their autophagy activation efficacy in cultured dermal fibroblast. The stimulation of autophagy flux by the selected extracts was further confirmed both by the expression of proteins associated with the autophagy signals and by electron microscope. Crepidiastrum denticulatum (CD) extract treated cells showed the highest autophagic vacuole formation in the non-cytotoxic range. The phosphorylation of adenosine monophosphate kinase (AMPK), but not the inhibition of mammalian target of rapamycin (mTOR), was observed by CD-extract treatment. Its anti-pollution effects were further evaluated with model compounds, benzo[a]pyrene (BaP) and cadmium chloride (CdCl2), and a CD extract treatment resulted in both the protection of cytotoxicity and a reduction of proinflammatory cytokines. These results suggest that the autophagy activators can be a new protection regimen for anti-pollution. Therefore, CD extract can be used for anti-inflammatory and anti-pollution cosmetic ingredients.
Assuntos
Asteraceae/química , Poluentes Ambientais/efeitos adversos , Células Epidérmicas/citologia , Extratos Vegetais/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia , Benzopirenos/efeitos adversos , Cloreto de Cádmio/efeitos adversos , Células Cultivadas , Citocinas/metabolismo , Células Epidérmicas/efeitos dos fármacos , Células Epidérmicas/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Microscopia Eletrônica de Transmissão , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Extratos Vegetais/química , Serina-Treonina Quinases TOR/metabolismoRESUMO
KEY MESSAGE: Transcriptome analysis of Cd-treated switchgrass roots not only revealed novel switchgrass transcripts and gene structures but also highlighted the indispensable role of HSF/HSP network in switchgrass Cd tolerance. Switchgrass (Panicum virgatum L.), a C4 perennial tall grass, can be used for revegetation of Cd-contaminated soil. In the present study, a comparative transcriptome analysis of Cd-treated switchgrass roots was conducted. The result revealed a total of 462 novel transcripts and refined gene structures of 2337 transcripts. KEGG pathway and Gene Ontology analyses of the differentially expressed genes (DEGs) suggested that activation of redox homeostasis and oxidation-related metabolic processes were the primary response to Cd stress in switchgrass roots. In particular, 21 out of 23 differentially expressed shock transcription factor genes (HSFs), and 22 out of 23 differentially expressed heat shock protein genes (HSPs) had increased expression levels after Cd treatment. Furthermore, over-expressing one HSP-encoding gene in Arabidopsis significantly improved plant Cd tolerance. The result highlighted the activation of the redox homeostasis and the involvement of the HSF/HSP network in re-establishing normal protein conformation and thus cellular homeostasis in switchgrass upon Cd stress. These DEGs, especially those of the HSF/HSP network, could be used as candidate genes for further functional studies toward improved plant Cd tolerance in switchgrass and related species.
Assuntos
Cádmio/efeitos adversos , Fatores de Transcrição de Choque Térmico/metabolismo , Proteínas de Choque Térmico/metabolismo , Panicum/genética , Raízes de Plantas/genética , Transcriptoma , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Arabidopsis/fisiologia , Cloreto de Cádmio/efeitos adversos , Expressão Gênica , Ontologia Genética , Fatores de Transcrição de Choque Térmico/genética , Proteínas de Choque Térmico/genética , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Panicum/efeitos dos fármacos , Panicum/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/fisiologia , RNA de Plantas/química , RNA de Plantas/genética , Análise de Sequência de RNA , Estresse FisiológicoRESUMO
BACKGROUND: Vacuolar H+-ATPase (V-ATPase) is a vital protein complex involved in abiotic stress response in plants. The G subunit of Juglans regia (JrVHAG1) was previously identified as a drought tolerance-related gene involved in the ABA (abscisic acid)-signal pathway. Heavy metal stress is becoming a major detriment for plant growth, development, and production. In order to understand the role of JrVHAG1, the potential function mechanism of JrVHAG1 exposed to CdCl2 stress was confirmed in this study. RESULTS: Transcription of JrVHAG1 was induced by ABA and increased to 58.89-fold (roots) and 7.38-fold (leaves) and by CdCl2 to 2.65- (roots) and 11.42-fold (leaves) relative to control, respectively. Moreover, when treated simultaneously with ABA and CdCl2 (ABA+CdCl2), JrVHAG1 was up-regulated to 110.13- as well as 165.42-fold relative to control in the roots and leaves, accordingly. Compared to the wild type (WT) Arabidopsis plants, the transgenic plants with overexpression of JrVHAG1 (G2, G6, and G9) exhibited increased seed germination rate, biomass accumulation, proline content, and activities of superoxide dismutase (SOD) and peroxidase (POD) under ABA, CdCl2, and ABA+CdCl2 treatments. In contrast, the reactive oxygen species (ROS) staining, malondialdehyde (MDA) content, hydrogen dioxide (H2O2) content, as well as electrolyte leakage (EL) rates of transgenic seedlings were all lower than those of WT exposed to ABA, CdCl2 and ABA+CdCl2 stresses. Furthermore, a 1200 bp promoter fragment of JrVHAG1 was isolated by analyzing the genome of J. regia, in which the cis-elements were identified. This JrVHAG1 promoter fragment showed expression activity that was enhanced significantly when subjected to the above treatments. Yeast one-hybrid assay and transient expression analysis demonstrated that JrMYB2 specifically bound to the MYBCORE motif and shared similar expression patterns with JrVHAG1 under ABA, CdCl2 and ABA+CdCl2 stress conditions. CONCLUSIONS: Our results suggested that the JrVHAG1 gene functions as a CdCl2 stress response regulator by participating in ABA-signal pathway and MYB transcription regulation network. JrVHAG1 gene is a useful candidate gene for heavy metal stress tolerance in plant molecular breeding.
Assuntos
Arabidopsis/genética , Cloreto de Cádmio/efeitos adversos , Regulação da Expressão Gênica de Plantas , Juglans/fisiologia , Proteínas de Plantas/genética , ATPases Vacuolares Próton-Translocadoras/genética , Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Cádmio/efeitos adversos , Juglans/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Transdução de Sinais , Transativadores/genética , Transativadores/metabolismo , ATPases Vacuolares Próton-Translocadoras/metabolismoRESUMO
The extraction of Periploca polysaccharides (PAPS) was optimized using the response surface methodology. The influence of solvent, liquid-solid ratio and extraction time on polysaccharide yield was evaluated using a full factorial design (23). Also, PAPS extract did not induce a cytotoxic effect on HepG2 cells within the range of tested concentrations (0-250µgmL-1). Herein, the pre-treatment with PAPS extract (100µgmL-1) reduced cell mortality. Furthermore, the in vivo antioxidant activity of PAPS extract was investigated in rats. The oral administration of 250mgkg-1 body weight of PAPS extract administered above a period of 10 weeks to cadmium chloride (CdCl2) induced toxicity in male Wistar rats, markedly decreased the content of MDA and protein damage in liver tissue, and enhanced liver function parameters (ALAT, ASAT and bilirubin), as well as the activities of hepatic antioxidant status (SOD, CAT, GPx and GSH). Finally, the examination of liver histopathology confirmed that PAPS ameliorate the alteration of liver tissue caused by exposition to cadmium.
Assuntos
Antioxidantes/farmacologia , Quelantes/farmacologia , Periploca/química , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Animais , Antioxidantes/química , Cádmio/efeitos adversos , Cloreto de Cádmio/efeitos adversos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Quelantes/química , Fracionamento Químico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Cromatografia Gasosa-Espectrometria de Massas , Células Hep G2 , Humanos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Polissacarídeos/química , RatosRESUMO
Inorganic nanomedicines in the fight against cancer have progressed rapidly during recent years, with the synergistic advantages of multifunctional nanosystems compared to single component. Herein, a drug-combination opinion was introduced into "nanomedicine" based on the understanding of Trojan horse-anti-tumor mechanism of inorganic nano-medicines. Moreover, we reported the green and facile synthesis route of mono-dispersed and rod-like zein-conjugated ZnO/Cd(OH)Cl hierarchical nanocomposites. We found that the nanocomposites exhibited high-efficiency killing ability to tumor cells through lipid peroxidation mediated-membrane disintegration route. The safety studies in BALB/c mice didn't detect injection anaphylaxis, hemolysis and cytotoxicity. More interestingly, the nano-composites could specially accumulate in liver and kidney, which will be helpful for targeting cure to these regional cancers.
Assuntos
Antineoplásicos/metabolismo , Cloreto de Cádmio/metabolismo , Nanocompostos/administração & dosagem , Nanomedicina , Zeína/metabolismo , Óxido de Zinco/metabolismo , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Cloreto de Cádmio/administração & dosagem , Cloreto de Cádmio/efeitos adversos , Cloreto de Cádmio/farmacocinética , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Rim/metabolismo , Fígado/metabolismo , Camundongos Endogâmicos BALB C , Nanocompostos/efeitos adversos , Zeína/administração & dosagem , Zeína/efeitos adversos , Zeína/farmacocinética , Óxido de Zinco/administração & dosagem , Óxido de Zinco/efeitos adversos , Óxido de Zinco/farmacocinéticaRESUMO
Cadmium is a widely used heavy metal in industry and affects the male reproductive system of animals, including humans, as a result of occupational and environmental exposures. However, the molecular mechanism underlying its effect on steroidogenesis in gonads remains unclear. In this study, we demonstrated that exposure of K28 mouse testicular Leydig tumor cells to cadmium led to a significant increase in the mRNA level, promoter activity and protein level of the steroidogenic acute regulatory protein (StAR), an essential factor for steroid biosynthesis. It has been well documented that StAR gene transcription is regulated by multiple transcription factors, including cAMP-responsive element binding protein (CREB) family members and SF-1. Cadmium treatment caused an increase in CREB phosphorylation but did not alter the CREB protein level in the nucleus. EMSA studies revealed that cadmium-induced phosphorylated CREB formed specific complexes with the proximal region of the StAR gene promoter. Furthermore, co-transfection with a CREB expression plasmid significantly increased cadmium-induced StAR promoter activity. However, the nuclear level and the affinity of SF-1 protein for the StAR proximal promoter were dramatically decreased upon exposure to cadmium. Taken together, these results suggest that cadmium up-regulates StAR gene expression through phosphorylated CREB rather than through SF-1 in mouse testicular Leydig cells.
Assuntos
Cloreto de Cádmio/efeitos adversos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Fosfoproteínas/genética , Transcrição Gênica/genética , Regulação para Cima/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Células Intersticiais do Testículo , Masculino , Camundongos , Fosforilação , Fator Esteroidogênico 1/metabolismoRESUMO
Cadmium (Cd) is a heavy metal widely used or effused by industries. Serious environmental Cd pollution has been reported over the past two centuries, whereas the mechanisms underlying Cd-mediated diseases are not fully understood. Interestingly, an increase in reactive oxygen species (ROS) after Cd exposure has been shown. Our group has demonstrated that sleep is triggered via accumulation of ROS during neuronal activities, and we thus hypothesize the involvement of Cd poisoning in sleep-wake irregularities. In the present study, we analyzed the effects of Cd intake (1-100 ppm CdCl2 in drinking water) on rats by monitoring sleep encephalograms and locomotor activities. The results demonstrated that 100 ppm CdCl2 administration for 28 h was sufficient to increase non-rapid-eye-movement (non-REM) sleep and reduce locomotor activities during the night (the rat active phase). In contrast, free-running locomotor rhythms under constant dim red light and their re-entrainment to 12:12-h light/dark cycles were intact under chronic (1 month) 100 ppm CdCl2 administrations, suggesting a limited influence on circadian clock movements at this dosage. The relative amount of oxidized glutathione increased in the brain after the 28-h 100 ppm CdCl2 administrations similar to the levels in cultured astrocytes receiving H2O2 or CdCl2 in culture medium. Therefore, we propose Cd-induced sleep as a consequence of oxidative stress. As oxidized glutathione is an endogenous sleep substance, we suggest that Cd rapidly induces sleepiness and influences activity performance by occupying intrinsic sleep-inducing mechanisms. In conclusion, we propose increased non-REM sleep during the active phase as an index of acute Cd exposure.
Assuntos
Cloreto de Cádmio/administração & dosagem , Cloreto de Cádmio/efeitos adversos , Água Potável/química , Fases do Sono/efeitos dos fármacos , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Ritmo Circadiano/efeitos dos fármacos , Genes Precoces/efeitos dos fármacos , Glutationa/metabolismo , Dissulfeto de Glutationa/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismoRESUMO
The effects of long-term (1 yr) exposure to low doses of cadmium (Cd) dissolved in drinking water on selected biochemical and antioxidant parameters were studied in Wistar rats. Rats were divided into four groups: male control group (C-m), female control group (C-f), male Cd-exposed group (Cd-m), and female Cd-exposed group (Cd-f). Cd groups were exposed to Cd dissolved in drinking water (cadmium dichloride 4.8 mg CdCl2/L, i.e., 2.5 mg Cd/L, 500-fold of maximal allowable concentration for potable water). The experiment was terminated on d 370. In all groups, biochemical parameters (total protein [TP], albumin, alanine aminotransferase, aspartate aminotransferase, glucose, cholesterol, triacylglycerols, urea, and creatinine) and antioxidant parameters (glutathione peroxidase, superoxide dismutase, and total antioxidant capacity) were measured in the blood. Total protein and albumin concentrations were decreased significantly in the Cd-m group. Other biochemical parameters did not change in Cd groups compared to control groups. Superoxide dismutase fell significantly in both male and female Cd-exposed groups. Activity of glutathione peroxidase was markedly lower in Cd-exposed groups. Total antioxidant capacity increased significantly in Cd-f group. These results suggest that chronic low-dose oral Cd exposure induces oxidative stress.
Assuntos
Compostos de Cádmio/efeitos adversos , Alanina Transaminase/sangue , Animais , Antioxidantes/análise , Aspartato Aminotransferases/sangue , Glicemia/análise , Glicemia/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Cloreto de Cádmio/administração & dosagem , Cloreto de Cádmio/efeitos adversos , Compostos de Cádmio/administração & dosagem , Creatinina/sangue , Feminino , Glutationa/sangue , Masculino , Peroxidase/sangue , Ratos , Ratos Wistar , Albumina Sérica/análise , Albumina Sérica/efeitos dos fármacos , Superóxido Dismutase/sangue , Triglicerídeos/sangueRESUMO
Antimutagenic effects of polypeptides isolated from Triticum kiharae wheat plantule extracts have been studied on human cells exposed to cadmium chloride. The most effective polypeptide Tk-AMP-BP ß -purothionin exhibited higher antimutagenic activity than wheat water extract and another peptide isolated from the same wheat species, Tk-AMP-γ 2 defensin; it also produced a pronounced antioxidant effect. This polypeptide can be used as a preventive agent for reducing the mutagenic potential of some environmental pollutants and for correction of human diseases associated with the defense system defects.
Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Proteínas de Plantas/farmacologia , Triticum/química , Cloreto de Cádmio/efeitos adversos , Células Cultivadas , Defensinas/farmacologia , Humanos , Medições Luminescentes , Linfócitos/efeitos dos fármacosRESUMO
Potential risk associated with new nanomaterial exposure needs to be assessed. This in vivo study investigated pulmonary effects of engineered cadmium-containing silica nanoparticles Cd/SiNPs (1 mg/rat), silica SiNPs (600 µg/rat) and CdCl2 (400 µg/rat) 1, 7 and 30 days after intratracheal instillation. Comprehensive histopathological and immunocytochemical characterization of lung damage in terms of apoptosis, cell proliferation, inflammation, fibrosis and metabolism were obtained. After exposure to all treatments, lung parenchyma showed injury patterns characterized by collapsed alveoli, inflammation, granuloma formation, thickened alveolar septa and bronchiolar epithelium exfoliation. Type II pneumocytes, containing scarcely surfactant-lamellated bodies, were also observed. Apoptotic phenomena enhanced as following, Cd/SiNPs>CdCl2> SiNPs. In parallel with these findings, a significant increase of PCNA-immunoreactive cells was detected together with high mitotic activity. Cellular localization and distribution of IL-6, IP-10 and TGF-ß1 revealed an increased expression of these cytokines as evidence of an enhanced cellular inflammatory response. CYP450-immunoreactivity was also enhanced, at bronchiolar (e.g. Clara cells) and alveolar (e.g. macrophages) level after both Cd/SiNPs and CdCl2. These overall effects were observed acutely and lasted until the 30th day, with Cd/SiNPs producing the most marked effects. Collagen-immunolabelling changed particularly 7 and 30 days after Cd/SiNPs, when a strong stromal fibrogenic reaction occurred. The present findings suggest that Cd/SiNPs produce significantly greater pulmonary alterations than either SiNPs or CdCl2 under the present experimental conditions.