RESUMO
Skin permeation and distribution of three of the most common skin sensitizers was investigated using a previously developed animal-free exposure method combined with imaging mass spectrometry. Nickel, cobalt, and chromium (III) salts were dissolved in a buffer and exposed to human skin ex vivo, to be analyzed using time of flight secondary ion mass spectrometry (ToF-SIMS). Our findings demonstrate that metal haptens mainly accumulated in the stratum corneum, however all three metal sensitizers could also be detected in the epidermis. Cobalt and chromium (III) species penetrated into the epidermis to a larger extent than nickel species. The degree of penetration into the epidermis is suggested to be affected by the sensitization potency of the metal salts, as well as their speciation, i.e. the amount of the respective metal present in the solution as bioaccessible and solubilised ions. Our method provided permeation profiles in human skin for known sensitizers, on a level of detail that is not possible to achieve by other means. The findings show that the permeation profiles are different, despite these sensitizers being all metal ions and common causes of contact allergy. Studying skin uptake by only considering penetration through the skin might therefore not give accurate results.
Assuntos
Cloretos/farmacologia , Compostos de Cromo/farmacologia , Cobalto/farmacologia , Haptenos/farmacologia , Níquel/farmacologia , Pele/metabolismo , Feminino , Humanos , Técnicas In Vitro , Espectrometria de Massas , Pele/diagnóstico por imagem , Absorção CutâneaRESUMO
The aim of the study was to determine how a high-fat diet supplemented with various forms of chromium affects hematological and immune parameters of the blood of rats. The rats received a standard diet or a high-fat diet supplemented with chromium at 0.3 mg/kg body weight (BW) in the form of chromium(III) picolinate, chromium(III)-methionine or nano-sized chromium. Selected hematological parameters were determined in the blood of the rats, including total white blood cell (WBC) count, leukogram, red blood cell (RBC) count, hemoglobin level (HGB), hematocrit (HCT), platelet count (PLT) and platelet percentage (PCT), as well as immune parameters: levels of immunoglobulins A and E (IgA and IgE), interleukin-6 (IL-6), interleukin-2 (IL-2), and tumor necrosis factor α (TNF-α); activity of ceruloplasmin (Cp); and levels of caspase 3 and 8 (Casp3 and Casp8). Feeding rats a high-fat diet increased blood markers of induction of inflammation, ie pro-inflammatory cytokines IL-6 and TNF-α, and also significantly increased IgE. The diet had no effect on the blood count, except for an increase in the number of neutrophils. The chromium compounds tested, particularly Cr-Met and Cr-NPs, stimulated the immune system of the rats, as indicated by increased concentrations of IgA, IgE, IL-2, IL-6, TNF-α, and Cp. Given the increase in inflammatory mediators induced by chromium, it should not be used to mitigate the effects of a high-fat diet. Moreover, chromium picolinate and chromium nanoparticles were shown to increase the content of caspase 3 and 8 in the blood of rats, which indicates a pro-apoptotic effect. The effects of the use of chromium nanoparticles include reductions in the WBC count and in the thrombocyte count (leuko- and thrombopenia). Taking account these data the use of chromium as dietary supplement should be reconsidered.
Assuntos
Biomarcadores/sangue , Fenômenos Fisiológicos Sanguíneos/efeitos dos fármacos , Compostos de Cromo/farmacologia , Citocinas/sangue , Dieta Hiperlipídica , Mediadores da Inflamação/sangue , Animais , Análise Química do Sangue , Testes Hematológicos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , RatosRESUMO
OBJECTIVE: Our published literature indicated that chromium citrate could regulate the glycemic index in alloxaninduced diabetic mice. The present study investigated the mechanism of chromium citrate in insulin resistance (IR) buffalo rat liver (BRL) cells. MATERIALS And METHODS: Chromium citrate was synthesized in our laboratory. BRL cells were purchased from the Chinese Academy of Sciences Cell Bank. The glucose transport and IR affected by chromium citrate in BRL cells were examined. The Thiazolyl Blue Tetrazolium Bromide (MTT) and glucose assay experiments were measured by microplate ELISA reader. The protein kinase B (Akt), glucose transporter-4 (Glut4), and phosphor-AMP-activated protein kinase ß1 levels were tested by Western blot, and the mRNA expression of glucose transport proteins (Akt2, Glut4, and AMPactivated protein kinase α2 (AMPKα2)) and insulin sensitivity proteins (insulin receptor substrate1 (IRS-1), phosphatidylinositol 3 kinase (PI3K), and peroxisome proliferator-activated receptor γ (PPARγ)) was measured by reverse transcription-polymerase chain reaction. RESULTS: The results indicated that the glucose absorption level of chromium citrate groups was higher than model group significantly. It demonstrated that chromium citrate could significantly improve glucose absorption in IR BRL cells. The Akt, Glut4, and phosphor-AMPKß1 levels in chromium citrate groups (at doses of 0.4, 0.2, and 0.1 µg Cr/mL) were markedly improved when compared with the other experiment groups, and chromium citrate could more effectively increase the Akt level than chromium trichloride. In addition, the mRNA expression of Akt2, Glut4, and AMPKα2 in chromium citrate groups was significantly improved when contrasted with model group. CONCLUSION: The consequences illustrated that chromium citrate can affect the IR BRL cells' ameliorating glucose transport and IR.
Assuntos
Compostos de Cromo/farmacologia , Glucose/metabolismo , Resistência à Insulina , Fígado/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Transportador de Glucose Tipo 4/genética , Proteínas Substratos do Receptor de Insulina/genética , Fígado/citologia , PPAR gama/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos Endogâmicos BUFRESUMO
Green synthesis of nanoparticles using plants has become a promising substitute for the conventional chemical synthesis methods. In the present study, our aim was to synthesize chromium oxide nanoparticles (Cr2 O3 NPs) through a facile, low-cost, eco-friendly route using leaf extract of Rhamnus virgata (RV). The formation of Cr2 O3 NPs was confirmed and characterized by spectroscopic profile of UV-Vis, EDX, FTIR, and XRD analyses. The UV-visible spectroscopy has confirmed the formation of Cr2 O3 NPs by the change of color owing to surface plasmon resonance. The bioactive functional groups present in the leaf extract of RV involved in reduction and stabilization of Cr2 O3 NPs were determined by FTIR analysis. Based on XRD analysis, crystalline nature of Cr2 O3 NPs was determined. The morphological shape and elemental composition of Cr2 O3 NPs were investigated using SEM and EDX analyses, respectively. With growing applications of Cr2 O3 NPs in biological perspectives, Cr2 O3 NPs were evaluated for diverse biopotentials. Cr2 O3 NPs were further investigated for its cytotoxicity potentials against HepG2 and HUH-7 cancer cell lines (IC50 : 39.66 and 45.87 µg/ml), respectively. Cytotoxicity potential of Cr2 O3 NPs was confirmed against promastigotes (IC50 : 33.24 µg/ml) and amastigotes (IC50 : 44.31 µg/ml) using Leishmania tropica (KMH23 ). The Cr2 O3 NPs were further evaluated for antioxidants, biostatic, alpha-amylase, and protein kinase inhibition properties. Biocompatibility assay was investigated against human macrophages which confirmed the nontoxic nature of Cr2 O3 NPs. Overall, the synthesized Cr2 O3 NPs are biocompatible and nontoxic and proved to possess significant biopotentials. In future, different in vivo studies are needed to fully investigate the cytotoxicity and mechanism of action associated with these Cr2 O3 NPs.
Assuntos
Compostos de Cromo/química , Química Verde , Nanopartículas Metálicas/química , Compostos Fitoquímicos/química , Extratos Vegetais/química , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Compostos de Cromo/farmacologia , Cristalização , Células Epiteliais/efeitos dos fármacos , Células Hep G2 , Humanos , Leishmania tropica/efeitos dos fármacos , Microscopia Eletrônica de Varredura , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Chromium(III) is one of the most controversial biometals. Although, it is no longer on the list of minerals necessary for the proper functioning of the human body, and its pharmacological effect is still under discussion. One of the purposes of Cr(III) administration is to use it in patients with mood disorders and it is strictly related to its pharmacological, not dietary effect. This is because its high doses are necessary to obtain the results and additionally, no deficiencies in human population have been noted. In this study, the affinity of chromium(III) to selected receptors and transporters in the rat brain was evaluated, and the effect of the 14-day administration of this metal was assessed on the density of selected receptors. All analyses were performed in vitro using radioligand binding assays, and the results indicated lack of affinity to ß1 and α1 receptors and serotonin transporter (SERT), furthermore very weak affinity to the 5-HT1A receptor (30% inhibition at 10-4 and 10-5 M). Analysis of the α1 and ß1 adrenergic receptor density indicated lack of any adaptive effects after 14 days of Cr(III) administration through intraperitoneal injections (doses 6 and 12 mg/kg). The antidepressant activity of chromium(III) indicated in clinical trials concerned patients with atypical, seasonal, or dystonic symptoms. This effect, as it seems based on the presented results, does not depend on direct affinity to serotonin receptors and transporter nor is the result of adaptive changes in the adrenoreceptor system.
Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Cloretos/administração & dosagem , Cloretos/farmacologia , Compostos de Cromo/administração & dosagem , Compostos de Cromo/farmacologia , Receptores Adrenérgicos alfa 1/análise , Receptores Adrenérgicos beta 1/análise , Proteínas da Membrana Plasmática de Transporte de Serotonina/análise , Animais , Cloretos/química , Compostos de Cromo/química , Injeções Intraperitoneais , Masculino , Transporte Proteico , Ratos , Ratos WistarRESUMO
Atypical antipsychotics, such as olanzapine, are commonly prescribed to patients with schizophrenic symptoms and other psychiatric disorders. However, weight gain and metabolic disturbance cause adverse effects, impair patient compliance and limit clinical utility. Thus, a better understanding of treatment-acquired adverse effects and identification of targets for therapeutic intervention are believed to offer more clinical benefits for patients with schizophrenia. Beyond its nutritional effects, studies have indicated that supplementation of chromium brings about beneficial outcomes against numerous metabolic disorders. In this study, we investigated whether olanzapine-induced weight gain and metabolic disturbance involved chromium dynamic mobilization in a female Sprague-Dawley rat model, and whether a dietary supplement of chromium improved olanzapine-acquired adverse effects. Olanzapine medicated rats experienced weight gain and adiposity, as well as the development of hyperglycemia, hyperinsulinemia, insulin resistance, hyperlipidemia, and inflammation. The olanzapine-induced metabolic disturbance was accompanied by a decrease in hepatic Akt and AMP-activated Protein Kinase (AMPK) actions, as well as an increase in serum interleukin-6 (IL-6), along with tissue chromium depletion. A daily intake of chromium supplements increased tissue chromium levels and thermogenic uncoupling protein-1 (UCP-1) expression in white adipose tissues, as well as improved both post-olanzapine weight gain and metabolic disturbance. Our findings suggest that olanzapine medicated rats showed a disturbance of tissue chromium homeostasis by inducing tissue depletion and urinary excretion. This loss may be an alternative mechanism responsible for olanzapine-induced weight gain and metabolic disturbance.
Assuntos
Adiposidade/efeitos dos fármacos , Antipsicóticos/efeitos adversos , Cloretos/farmacologia , Compostos de Cromo/farmacologia , Hiperglicemia/metabolismo , Hiperinsulinismo/metabolismo , Hiperlipidemias/metabolismo , Olanzapina/efeitos adversos , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Adiposidade/genética , Administração Oral , Animais , Cloretos/metabolismo , Compostos de Cromo/metabolismo , Feminino , Regulação da Expressão Gênica , Hiperglicemia/induzido quimicamente , Hiperglicemia/genética , Hiperglicemia/prevenção & controle , Hiperinsulinismo/induzido quimicamente , Hiperinsulinismo/genética , Hiperinsulinismo/prevenção & controle , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/genética , Hiperlipidemias/prevenção & controle , Inflamação , Resistência à Insulina/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Aumento de Peso/efeitos dos fármacosRESUMO
BACKGROUND: Bone morphogenetic proteins play an important role as osseointegrative factors. It is used widely in orthopedic research and surgery to enhance the osseointegrative potential of implants, e.g., in spinal fusion or alveolar socket augmentation. The aim of the present study was to investigate the benefit of rhBMP-2 on a titan plasma spray (TPS) layer after a special modification with chromosulfuric acid (CSA) at different postoperative times, regarding osseoconduction and osseoinduction. METHODS: We allocated 27 Göttinger minipigs into three groups consisting of nine animals each. They received four dumbbell-shaped implants in the metaphyseal parts of the femora. The implants had a TPS surface with (CSA group) and without a CSA treatment (TPS group). The former received an additional layer of BMP-2 (BMP-2 group). For the assessment of osseointegration after healing periods of 4, 8, and 12 weeks, histomorphometry was applied to undecalcified specimens after staining according to Masson-Goldner. An intravital labeling with different fluorochromes was used in the gap model. A multivariable analysis with repeated measurement design was performed for statistical evaluation. RESULTS: We observed several statistical differences in a three-way ANOVA. The comparison between the BMP-2 and the TPS group (two-way ANOVA) showed statistically significant differences in terms of the osseoinduction (osteoid volume), and pronounced for the osseoconduction (bone and osteoid ongrowth), in favor of the BMP-2 group. In the pairwise comparison between BMP-2 and CSA (two-way ANOVA), no statistical significance occurred. The intravital staining with tetracycline, calcein green, and xylenol orange revealed no considerable differences between the groups. CONCLUSION: BMP-2, covalently bound on a CSA-treated TPS surface, has positive effects on the osseointegration in the large animal bone gap-healing model over the observation period of 12 weeks.
Assuntos
Proteína Morfogenética Óssea 2 , Compostos de Cromo , Osseointegração , Próteses e Implantes , Sulfatos , Titânio , Animais , Proteína Morfogenética Óssea 2/administração & dosagem , Compostos de Cromo/farmacologia , Modelos Animais de Doenças , Fêmur , Proteínas Recombinantes , Sulfatos/farmacologia , Propriedades de Superfície , Suínos , Porco Miniatura , Fator de Crescimento Transformador betaRESUMO
Ionizing radiation plays a key role in the adaptation of an individual organism to environmental pollution, at the same time, it has biological effects that depend on radiation intensity or dose rate (DR). Although the effect of DR has been studied in vitro, the phenomenon known as the inverse effect of DR, which indicates as it decreases that the induction of damage is greater, has not been widely studied in vivo. The present study is aimed to test 0.5 and 1 Gy in somatic cells of the wing of D. melanogaster, administered at 5.4 or 34.3 Gy/h and from 0.037 to 0.3 mM of CrO3 as conditioning treatment. No changes were found in larva-to-adult viability. A protective as well as a cross effect of pre-exposure to different DR and CrO3 concentrations against genetic damage induced by 20 Gy or 1 mM CrO3 was evident.
Assuntos
Compostos de Cromo/farmacologia , Drosophila melanogaster/genética , Asas de Animais/citologia , Animais , Meios de Cultivo Condicionados , Dano ao DNA/efeitos dos fármacos , Relação Dose-Resposta à Radiação , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/efeitos da radiação , Feminino , Tolerância a Radiação , Radiação Ionizante , Asas de Animais/efeitos dos fármacos , Asas de Animais/efeitos da radiaçãoRESUMO
Human 8-oxoguanine DNA glycosylase (hOGG1) plays a significant role in maintaining the genomic integrity of living organisms for its capability of repairing DNA lesions. Accurate detection of hOGG1 activity would greatly facilitate the screening and early diagnosis of diseases. In this work, we report a nanopore-based sensing strategy to probe the hOGG1 activity by employing the enzyme-catalytic cleavage reaction of DNA substrate. The hOGG1 specifically catalyzed the removal of the 8-hydroxyguanine (8-oxoG) and cleaved the DNA substrates immobilized on magnetic beads, thereby releasing the output DNA which would quantitatively produce the signature current events when subjected to α-hemolysin (α-HL) nanopore test. The approach enables the sensitive detection of hOGG1 activity without the need of any labeling or signal amplification route. Furthermore, the method can be applied to assay the inhibition of hOGG1 and evaluate the activity of endogenous hOGG1 in crude cell extracts. Importantly, since DNAs with specific sequences are the catalytic substrates of a wide variety of enzymes, the proposed strategy should be universally applicable for probing the activities of different types of enzymes with nanopore sensors.
Assuntos
Técnicas Biossensoriais/métodos , DNA Glicosilases/metabolismo , Proteínas Hemolisinas/química , Nanoporos , Células A549 , Extratos Celulares/química , Cloretos/farmacologia , Compostos de Cromo/farmacologia , DNA Glicosilases/antagonistas & inibidores , Reparo do DNA , DNA Catalítico/metabolismo , Guanina/análogos & derivados , Guanina/química , Humanos , Sensibilidade e Especificidade , TemperaturaRESUMO
This experiment was carried out to investigate the combination effects of organic and inorganic chromium (Cr) on egg production, egg quality, reproductive response, and immune status of breeder quails and their offspring under heat stress. A total of 140 7-week-old Japanese breeder quails (120 females and 20 males) according to a completely randomized design were used in four treatment groups (five replicate and seven birds per each) lasted for 8 weeks. Quails exposed to 35 °C for 8 h/day for induction of cyclic heat stress treatments consisted of diets supplemented with (1) 1 mg CrCl3 per kilogram of diet as control (CNT); (2) 1 mg Cr-L-Met per kilogram of diet as organic Cr (OCr); (3) 0.5 mg CrCl3 plus 0.5 mg Cr-L-Met per kilogram of diet (ISO); (4) 1 mg CrCl3 plus 0.5 mg Cr-L-Met per kilogram of diet (On-top). Productive performance and egg quality parameters were determined weekly. Fertility, hatchability, and embryonic mortality were measured at the end of experiment. Humoral immunity was assessed by primary and secondary antibody titer in sheep red blood cells (SRBC) and Newcastle disease (ND) tests. Cell-mediated immunity was assessed by the cutaneous basophil hypersensitivity (CBH) test to phytohemagglutinin (PHA) at days 20 and 45 of age. White blood cell count and immunoglobulin Y (IgY) content in serum and yolk of breeders and in serum and yolk residues of offspring were also measured. Results showed that maximum egg production, egg shell thickness, and Haugh unit were observed in birds fed ISO and On-top diets (P ≤ 0.05). The highest (P ≤ 0.05) antibody levels in ND test were observed in birds fed with OCr, ISO, and On-top diets. The highest cellular response (P ≤ 0.05) was in 12 h after primary PHA injection and 12 and 24 h after secondary PHA injection in birds fed with On-top diets. The highest count of heterophil and (H/L) were gained in breeder quails fed with CNT diet, and the lowest of them were reached with On-top diet (P ≤ 0.05). Results showed that the highest IgY level in serum of breeder and their offspring and that of yolk suck and egg yolk were observed in birds fed with On-top diet (P ≤ 0.05). These results suggest that extra supplemental organic Cr in combination with CrCl3 could lead to higher egg production, egg quality, and immune status of breeder quails and their offspring.
Assuntos
Compostos de Cromo/farmacologia , Cromo/farmacologia , Temperatura Alta , Imunidade/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Reprodução/efeitos dos fármacos , Animais , Cromo/química , Coturnix , Ovos/análise , Ovos/normas , Ovos/estatística & dados numéricos , Feminino , Imunidade Celular/efeitos dos fármacos , Imunidade Materno-Adquirida/efeitos dos fármacos , Masculino , Estresse Fisiológico/efeitos dos fármacosRESUMO
The objective of this work is to detect the mode of damage caused by Cr(III), one of the widely used industrial pollutant on Bacillus subtilis-industrial strain 168 and Escherichia coli MTCC 40. Bioassays are very sensitive, precise, economical and rapid for detecting early stages of pollution. The detrimental effect of trivalent chromium becomes clear from the growth profile and growth inhibition studies. Mode of action of damage by trivalent chromium in bacterial model was found to be oxidative, as chromium is one of the redox active metals. The generation of reactive oxygen species (ROS) resulted in membrane damage which in turn had a detrimental effect on the membrane proteins as well as the DNA. The structural changes in the SEM and AFM images clearly reveals the damage caused by Cr(III) to the test bacterial models. Trivalent chromium causes greater DNA, protein and membrane damage in case of E. coli than B. subtilis. Membrane damage caused by ROS becomes evident from the production of Thiobarbituric acid reactive substances (TBARs) as the mechanism of killing followed by DNA damage and the production of elevated levels of stress proteins known as extracellular cellular proteins.
Assuntos
Bacillus subtilis/efeitos dos fármacos , Cloretos/farmacologia , Compostos de Cromo/farmacologia , Poluentes Ambientais/farmacologia , Escherichia coli/efeitos dos fármacos , Bacillus subtilis/fisiologia , Dano ao DNA , Escherichia coli/fisiologia , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Viabilidade Microbiana , Oxirredução , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismoRESUMO
The potential environmental risks of chromium oxide nanoparticles (Cr2O3 NPs) have caused great concerns. However, their possible impacts on activated sludge process are very limited. In this study, we carried out long-term exposure experiments to evaluate the influence of Cr2O3 NPs on wastewater nutrient removal, bacterial community and molecular ecological network (MEN) in the sequencing batch reactor (SBR). It was found that 1 mg/L Cr2O3 NPs increased the effluent concentrations of NO3--N and TP from 6.5 to 15.4 mg/L, and 0.6-2.7 mg/L, indicating the serious deterioration of denitrification and phosphorus removal. Cr2O3 NPs significantly decreased the bacterial richness in terms of the number of different OTUs (626 OTUs in Cr2O3 samples and 728 OTUs in controls). Detrended correspondence analysis (DCA) showed that the overall taxonomic structure of bacterial community was altered at Cr2O3 NPs in activated sludge systems. Further analysis revealed that three genera related to denitrification (Desulfovibrio, Pseudomonas and Hyphomicrobium) and two genera related to phosphorus removal (Accumulibacter and Rhodobacter) decreased significantly, which was consistent with the observed influences of Cr2O3 NPs on denitrification and phosphorus removal. MEN analysis showed that the overall architecture of the network under Cr2O3 NPs was substantially alerted. ß-Proteobacteria, playing an important role in nutrients removal, had less complex interactions in the presence of Cr2O3 NPs, which may be associated with the deterioration of denitrification and phosphorus removal. This study provides insights into our understanding of shifts in the bacteria community and their MEN under Cr2O3 NPs in activated sludge systems.
Assuntos
Bactérias/efeitos dos fármacos , Compostos de Cromo/farmacologia , Nanopartículas Metálicas/química , Esgotos/química , Reatores Biológicos/microbiologia , Desnitrificação/efeitos dos fármacos , Ecossistema , Fósforo/isolamento & purificação , Esgotos/microbiologia , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/análiseRESUMO
The aim of this study was to examine the effect of treating of chromium(III) and iron(III) and their combinations on Herpes Simplex Virus type 1 (HSV-1) and Bovine Viral Diarrhoea virus (BVDV) replication. The antiviral efficacies of chromium(III) and iron(III) on HSV-1 and BVDV were evaluated using Real Time PCR method. Moreover, the cytotoxicity of these microelements was examined using the MTT reduction assay. The IC50 (50% inhibiotory concentration) for the chromium chloride was 1100 µM for Hep-2 cells and 1400 µM for BT cells. The IC50 for the iron chloride was 1200 µM for Hep-2 cells and more than1400 µM for BT cells. The concentration-dependent antiviral activity of chromium chloride and iron chloride against HSV-1 and BVDV viruses was observed. In cultures simultaneously treated with (1) 200 µM of CrCl3 and 1000 µM of FeCl3, (2) 1000 µM of CrCl3 and 200 µM of FeCl3, (3) 400 µM of CrCl3 and 800 µM of FeCl3, (4) 800 µM of CrCl3 and 400 µM of FeCl3 a decrease in number of DNA or RNA copies was observed compared with control cells and cells incubated with chromium(III) and iron(III) used separately. The synergistic antiviral effects were observed for chromium(III) and iron(III) against HSV-1 and BVDV.
Assuntos
Antivirais/farmacologia , Cloretos/farmacologia , Compostos de Cromo/farmacologia , Vírus da Diarreia Viral Bovina Tipo 1/efeitos dos fármacos , Compostos Férricos/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Animais , Bovinos , Linhagem Celular , Linhagem Celular Tumoral , DNA Viral/antagonistas & inibidores , DNA Viral/biossíntese , Vírus da Diarreia Viral Bovina Tipo 1/genética , Vírus da Diarreia Viral Bovina Tipo 1/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/virologia , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/crescimento & desenvolvimento , Humanos , RNA Viral/antagonistas & inibidores , RNA Viral/biossínteseRESUMO
OBJECTIVE: The aim of the present study was to examine the effect of chromium disilicide and titanium nitride nanoparticles on the expression level of genes encoding important regulatory factors (IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK/NUAK2, CD36, and PECAM1/CD31) in mouse liver for evaluation of possible toxic effects of these nanoparticles. METHODS: Male mice received 20 mg chromium disilicide nanoparticles (45 nm) and titanium nitride nanoparticles (20 nm) with food every working day for 2 months. The expression of IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK, CD36, and PECAM1 genes in mouse liver was studied by quantitative polymerase chain reaction. RESULTS: Treatment of mice with chromium disilicide nanoparticles led to down-regulation of the expression of IGFBP2, IGFBP5, PECAM1, and SNARK genes in the liver in comparison with control mice, with more prominent changes for SNARK gene. At the same time, the expression of IGFBP3 and CD36 genes was increased in mouse liver upon treatment with chromium disilicide nanoparticles. We have also shown that treatment with titanium nitride nanoparticles resulted in down-regulation of the expression of IGFBP2 and SNARK genes in the liver with more prominent changes for SNARK gene. At the same time, the expression of IGFBP3, IGFBP4, and CD36 genes was increased in the liver of mice treated with titanium nitride nanoparticles. Furthermore, the effect of chromium disilicide nanoparticles on IGFBP2 and CD36 genes expression was significantly stronger as compared to titanium nitride nanoparticles. CONCLUSIONS: The results of this study demonstrate that chromium disilicide and titanium nitride nanoparticles have variable effects on the expression of IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK, CD36, and PECAM1 genes in mouse liver, which may reflect the genotoxic activities of the studied nanoparticles.
Assuntos
Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Nanopartículas , RNA Mensageiro/efeitos dos fármacos , Titânio/farmacologia , Animais , Antígenos CD36/efeitos dos fármacos , Antígenos CD36/genética , Compostos de Cromo/farmacologia , Regulação para Baixo , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/efeitos dos fármacos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/efeitos dos fármacos , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/efeitos dos fármacos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 4 de Ligação a Fator de Crescimento Semelhante à Insulina/efeitos dos fármacos , Proteína 4 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Fígado/metabolismo , Masculino , Camundongos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/efeitos dos fármacos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Reação em Cadeia da Polimerase , Proteínas Serina-Treonina Quinases/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Compostos de Silício/farmacologia , Regulação para CimaAssuntos
Anemia Falciforme/tratamento farmacológico , Vancomicina/administração & dosagem , Adulto , Anemia Falciforme/genética , Antibacterianos/administração & dosagem , Antibacterianos/metabolismo , Cloretos/farmacologia , Compostos de Cromo/farmacologia , Genótipo , Taxa de Filtração Glomerular , Humanos , Masculino , Estudos Retrospectivos , Vancomicina/metabolismo , Adulto JovemRESUMO
Present study was designed to evaluate the effect of chromium-d-phenylalanine complex (Cr (d-phe)3) on indomethacin-induced inflammatory bowel disease (IBD) in rats. Adult Wistar rats were pretreated with vehicle/Cr (d-phe)3 (30, 60 and 90µg/kg, p.o.) for 11days. On day 8 and 9, after one h of the above mentioned treatment, indomethacin (7.5mg/kg/day,s.c.) was administered to induce IBD. On day 12, blood samples were collected from animals for lactate dehydrogenase (LDH) estimation and ileum was isolated for macroscopic scoring, biochemical estimation (lipid peroxidation, reduced glutathione and myeloperoxidase activity) and histopathological study. Administration of indomethacin significantly altered the serum LDH, macroscopic and microscopic appearance and biochemical parameters in ileum tissue. Cr (d-phe)3, at all the tested doses, caused a significant reversal of changes induced by indomethacin. Present study demonstrates the protective effect of Cr (d-phe)3 against indomethacin-induced IBD in rats. The observed protective effect might be attributed to the antioxidant and anti-inflammatory properties of Cr (d-phe)3.
Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Compostos de Cromo/farmacologia , Indometacina/toxicidade , Doenças Inflamatórias Intestinais/induzido quimicamente , Fenilalanina/farmacologia , Animais , Compostos de Cromo/química , Glutationa , Peroxidação de Lipídeos , Peroxidase/metabolismo , Fenilalanina/química , Ratos , Ratos Wistar , Sulfassalazina/farmacologiaRESUMO
New binuclear chromium (III) niacinamide compound with chemical formula [Cr2(Nic)(Cl)6(H2O)4]·H2O was obtained upon the reaction of chromium (III) chloride with niacinamide (Nic) in methanol solvent at 60°C. The proposed structure was discussed with the help of microanalytical analyses, conductivity, spectroscopic (FT-IR and UV-vis.), magnetic calculations, thermogravimetric analyses (TG/TGA), and morphological studies (X-ray of solid powder and scan electron microscopy. The infrared spectrum of free niacinamide in comparison with its chromium (III) compound indicated that the chelation mode occurs via both nitrogen atoms of pyridine ring and primary -NH2 group. The efficiency of chromium (III) niacinamide compound in decreasing of glucose level of blood and HbA1c in case of diabetic rats was checked. The ameliorating gluconeogenic enzymes, lipid profile and antioxidant defense capacities are considered as an indicator of the efficiency of new chromium (III) compound as antidiabetic drug model.
Assuntos
Antioxidantes/farmacologia , Compostos de Cromo/química , Compostos de Cromo/farmacologia , Hipoglicemiantes/farmacologia , Niacinamida/química , Animais , Antioxidantes/química , Glicemia/metabolismo , Cloretos/química , Compostos de Cromo/administração & dosagem , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Glicogênio/metabolismo , Hipoglicemiantes/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Microscopia Eletrônica de Varredura , Niacinamida/farmacologia , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Difração de Raios XRESUMO
This study aimed to investigate the effects of chromic chloride (CrCl3) on Ca, Mg, Mn, Fe, Cu, and Zn contents in the brain and serum of chicken. Seventy-two chickens were randomly divided into four groups and treated with different doses of CrCl3 via drinking water: 0, 1/8, 1/4, and 1/2 LD50 for 42 days. The contents of the elements were evaluated through inductively coupled plasma mass spectrometry. Results showed that Cr contents in the brain and serum were higher than those in the control groups, although no significant dose-dependent changes (P > 0.05) in brain of the Cr-treated groups were observed at 42 days. As exposure time was prolonged and CrCl3 dosage was increased, Ca contents increased (P < 0.05). Mg and Cu contents in serum decreased; by contrast, Mg and Cu contents initially increased and then decreased in the brain. Fe and Zn contents in the serum increased; conversely, Fe and Zn contents in the brain decreased. CrCl3 exposure did not significantly affect Mn contents at 14 or 28 days, but significantly decreased (P < 0.05) at 42 days. Therefore, excess Cr3+ intake can disrupt absorption and deposition of other trace elements in the brain and serum; the blood-brain barrier may prevent the accumulation of these elements in the brain exposed to CrCl3.
Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Cloretos/administração & dosagem , Cloretos/farmacologia , Compostos de Cromo/administração & dosagem , Compostos de Cromo/farmacologia , Oligoelementos/sangue , Oligoelementos/metabolismo , Animais , Galinhas , Relação Dose-Resposta a Droga , Espectrometria de MassasRESUMO
Leishmania establishes a successful parasitism by evading both oxidative and non-oxidative killing pathways, and its drug resistance against the currently available therapeutics demands for a safe and cheap drug. Since the parasite synthesizes ergosterol instead of cholesterol, using the same biochemical pathway and enzymes, an inhibitor of HMG-CoA-Reductase, Lovastatin, has been tried for its anti-Leishmanial effect. Lovastatin, being an inhibitor of HMG-CoA-Reductase, inhibits infection by cholesterol depletion, while chromium chloride complexes, at their higher concentrations, are reported to exhibit cytotoxicity. In intracellular amastigotes, cytotoxicity has been checked by assessing various manifestation of cell death, viz. DNA fragmentation, AnnexinV-FITC binding and JC-1 fluorescence ratio. Release of hydrogen peroxide (HPO) and nitric oxide (NO) has been assessed in live cell. Lovastatin and CrCl3.6H2O in combination has appeared to be ineffective on promastigotes but has induced cytotoxic effect on the intracellular amastigotes through up-regulation of cellular signalling mechanisms. CrCl 3.6H2O stimulates generation of NO, leading to reduction of the number of intracellular amastigote, while Lovastatin shows HPO-mediated killing of the same, keeping the host cell unaffected. This novel therapeutic approach, involving two known safe compounds in suboptimal doses, may resolve human visceral Leishmaniasis.
Assuntos
Antiprotozoários/farmacologia , Apoptose/efeitos dos fármacos , Cloretos/farmacologia , Compostos de Cromo/farmacologia , Hipolipemiantes/farmacologia , Leishmania donovani/efeitos dos fármacos , Lovastatina/farmacologia , Colesterol/metabolismo , Técnicas de Cocultura , Combinação de Medicamentos , Sinergismo Farmacológico , Humanos , Peróxido de Hidrogênio/agonistas , Peróxido de Hidrogênio/metabolismo , Leishmania donovani/crescimento & desenvolvimento , Leishmania donovani/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/parasitologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Óxido Nítrico/agonistas , Óxido Nítrico/biossíntese , Testes de Sensibilidade Parasitária , Cultura Primária de Células , Células THP-1RESUMO
An experiment was conducted to investigate the effects of dietary chromium (Cr) source and concentration on growth performance, carcass traits, and some serum lipid parameters of broilers under normal rearing conditions for 42 days. A total of 252 1-day-old Cobb 500 commercial female broilers were randomly allotted by body weight (BW) to one of six replicate cages (six broilers per cage) for each of seven treatments in a completely randomized design involved in a 2 × 3 factorial arrangement of treatments with three Cr sources (Cr propionate (CrPro), Cr picolinate (CrPic), Cr chloride (CrCl3)) and two concentrations of added Cr (0.4 and 2.0 mg of Cr/kg) plus a Cr-unsupplemented control diet. The results showed that dietary Cr supplementation tended to increase the breast muscle percentage compared with the Cr-unsupplemented control group (P = 0.0784), while Cr from CrPic tended to have higher breast muscle percentage compared with Cr from CrCl3 (P = 0.0881). Chromium from CrPic also tended to increase the breast intramuscular fat (IMF) compared with Cr from CrCl3 (P = 0.0648). In addition, supplementation of 0.4 mg/kg Cr tended to decrease low-density lipoprotein cholesterol (LDL-C) (P = 0.0614). Compared with the control group, broilers fed Cr-supplemented diets had higher triglyceride (TG) (P = 0.0129) regardless of Cr source and Cr concentration. Chromium from CrPro and CrPic had lower total cholesterol (TC) compared with Cr from CrCl3 (P = 0.0220). These results indicate that dietary supplementation of Cr has effects on carcass characteristics and serum lipid parameters of broilers under normal rearing conditions, while supplementation of organic Cr can improve carcass characteristics and reduce the cholesterol content in serum.