RESUMO
The aim of our experiment was to evaluate the anticancer effect of bamboo salt (BS) on C57BL/6 mice in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon cancer model. BS, solar salt, and purified salt were evaluated for their protective effects during AOM/DSS-induced colon carcinogenesis in C57BL/6 mice. BS, especially after baking for nine separate intervals (BS9x), suppressed colon carcinogenesis in the mice. BS9x decreased colon length shortening, weight-to-length ratios, and tumor counts. Pathological evidence from histological evaluation by hematoxylin and eosin staining also revealed suppression of tumorigenesis. BS9x lowered serum levels of proinflammatory cytokines (TNF-α, IL-6, and IL-1ß) to close to those of the Normal group. Additionally, BS9x suppressed colon mRNA expression of proinflammatory factors and significantly regulated mRNA levels of the apoptosis-related factors, Bax and Bcl-2, and the cell cycle-related genes, p21 and p53. Additionally, immunohistochemistry showed that BS promoted p21 expression in the colon. Taken together, the results indicate that BS exhibited anticancer efficacy by modulating apoptosis- and inflammation-related gene expression during colon carcinogenesis in mice, and repetition in baking cycles of BS enhanced its anticancer functionality.
Assuntos
Carcinogênese/efeitos dos fármacos , Colite/tratamento farmacológico , Neoplasias do Colo/prevenção & controle , Cloreto de Sódio na Dieta/farmacologia , Animais , Anticarcinógenos/farmacologia , Apoptose/efeitos dos fármacos , Carcinogênese/metabolismo , Carcinogênese/patologia , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , Colo/anatomia & histologia , Colo/efeitos dos fármacos , Colo/patologia , Neoplasias do Colo/sangue , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Citocinas/sangue , Modelos Animais de Doenças , Células HT29 , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Proteína X Associada a bcl-2RESUMO
The chemopreventive effects of different types and quantities of kimchi prepared with different subingredients, including commercial kimchi (CK), standardized kimchi (SK), cancer-preventive kimchi (CPK), and anticancer kimchi (ACK), on colorectal carcinogenesis in mice were evaluated. The development of colon cancer was induced in male BALB/c mice with a single intraperitoneal injection of azoxymethane (AOM, 10 mg/kg body weight) and subsequent treatment with 2% dextran sulfate sodium (DSS) in drinking water for 7 days for two cycles. After exposure to AOM and DSS, treatment with the methanolic extracts from different kimchis, particularly 1.89 g/kg of ACK, significantly increased colon length, decreased the ratio of colon weight/length, and resulted in the lowest number of tumors compared with the other kimchi-treated groups. Histological observation revealed that ACK was able to suppress AOM- and DSS-induced colonic mucosal damage and neoplasia. ACK also significantly decreased the mRNA levels of proinflammatory cytokines (TNF-α, IL-6, and IFN-γ) as well as the mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase-2 (COX-2). In addition, the mRNA and protein expression of p53 and p21 was elevated in colon tissues from the ACK-treated mice compared with the other kimchi-treated groups. Our results suggest that kimchi exerted a suppressive effect on AOM- and DSS-induced colorectal carcinogenesis in the BALB/c mice. The anticancer effects of ACK were particularly potent. Thus, it is possible that the health-promoting subingredients added to ACK might be used to prevent colon carcinogenesis in humans.
Assuntos
Brassica/metabolismo , Neoplasias do Colo/prevenção & controle , Animais , Azoximetano , Brassica/microbiologia , Carcinogênese , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/dietoterapia , Neoplasias do Colo/metabolismo , Sulfato de Dextrana , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Gold nanoparticles are widely used in consumer products, including cosmetics, food packaging, beverages, toothpaste, automobiles, and lubricants. With this increase in consumer products containing gold nanoparticles, the potential for worker exposure to gold nanoparticles will also increase. Only a few studies have produced data on the in vivo toxicology of gold nanoparticles, meaning that the absorption, distribution, metabolism, and excretion (ADME) of gold nanoparticles remain unclear. RESULTS: The toxicity of gold nanoparticles was studied in Sprague Dawley rats by inhalation. Seven-week-old rats, weighing approximately 200 g (males) and 145 g (females), were divided into 4 groups (10 rats in each group): fresh-air control, low-dose (2.36 × 104 particle/cm3, 0.04 µg/m3), middle-dose (2.36 × 105 particle/cm3, 0.38 µg/m3), and high-dose (1.85 × 106 particle/cm3, 20.02 µg/m3). The animals were exposed to gold nanoparticles (average diameter 4-5 nm) for 6 hours/day, 5 days/week, for 90-days in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and lung function were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and organ weights were measured. Cellular differential counts and cytotoxicity measurements, such as albumin, lactate dehydrogenase (LDH), and total protein were also monitored in a cellular bronchoalveolar lavage (BAL) fluid. Among lung function test measurements, tidal volume and minute volume showed a tendency to decrease comparing control and dose groups during the 90-days of exposure. Although no statistically significant differences were found in cellular differential counts, histopathologic examination showed minimal alveoli, an inflammatory infiltrate with a mixed cell type, and increased macrophages in the high-dose rats. Tissue distribution of gold nanoparticles showed a dose-dependent accumulation of gold in only lungs and kidneys with a gender-related difference in gold nanoparticles content in kidneys. CONCLUSIONS: Lungs were the only organ in which there were dose-related changes in both male and female rats. Changes observed in lung histopathology and function in high-dose animals indicate that the highest concentration (20 µg/m3) is a LOAEL and the middle concentration (0.38 µg/m3) is a NOAEL for this study.
Assuntos
Ouro/administração & dosagem , Ouro/toxicidade , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/toxicidade , Administração por Inalação , Animais , Sangue/efeitos dos fármacos , Análise Química do Sangue , Peso Corporal , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Humanos , Rim/patologia , Rim/fisiologia , Pulmão/patologia , Pulmão/fisiologia , Masculino , Teste de Materiais , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Tamanho do Órgão , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Distribuição TecidualRESUMO
BACKGROUND: The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, consumer, medicinal, pesticide, and home products; however, silver nanoparticles remain a controversial area of research with respect to their toxicity in biological and ecological systems. RESULTS: This study tested the oral toxicity of silver nanoparticles (56 nm) over a period of 13 weeks (90 days) in F344 rats following Organization for Economic Cooperation and Development (OECD) test guideline 408 and Good Laboratory Practices (GLP). Five-week-old rats, weighing about 99 g for the males and 92 g for the females, were divided into four 4 groups (10 rats in each group): vehicle control, low-dose (30 mg/kg), middle-dose (125 mg/kg), and high-dose (500 mg/kg). After 90 days of exposure, clinical chemistry, hematology, histopathology, and silver distribution were studied. There was a significant decrease (P < 0.05) in the body weight of male rats after 4 weeks of exposure, although there were no significant changes in food or water consumption during the study period. Significant dose-dependent changes were found in alkaline phosphatase and cholesterol for the male and female rats, indicating that exposure to more than 125 mg/kg of silver nanoparticles may result in slight liver damage. Histopathologic examination revealed a higher incidence of bile-duct hyperplasia, with or without necrosis, fibrosis, and/or pigmentation, in treated animals. There was also a dose-dependent accumulation of silver in all tissues examined. A gender-related difference in the accumulation of silver was noted in the kidneys, with a twofold increase in female kidneys compared to male kidneys. CONCLUSIONS: The target organ for the silver nanoparticles was found to be the liver in both the male and female rats. A NOAEL (no observable adverse effect level) of 30 mg/kg and LOAEL (lowest observable adverse effect level) of 125 mg/kg are suggested from the present study.
Assuntos
Nanopartículas Metálicas/toxicidade , Prata/toxicidade , Animais , Ductos Biliares/efeitos dos fármacos , Ductos Biliares/patologia , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Rim/metabolismo , Masculino , Nível de Efeito Adverso não Observado , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344 , Prata/farmacocinética , Distribuição TecidualRESUMO
Mesotherapy and anti-obesity medications are gradually gaining worldwide popularity for purposes of body contouring and weight loss. Their adverse effects are various, but there is a tendency to disregard them. Ischemic colitis is one of the most common diseases associated with non-obstructive blood vessel disorders. However, there have been no case reports about the adverse effects resulting from mesotherapy only or in combination with anti-obesity medications. We report on an interesting case of ischemic colitis after mesotherapy combined with anti-obesity medications in a 39-year-old female who had no risk factors.
Assuntos
Fármacos Antiobesidade/efeitos adversos , Colite Isquêmica/etiologia , Técnicas Cosméticas/efeitos adversos , Obesidade/terapia , Administração Oral , Adulto , Antibacterianos/uso terapêutico , Fármacos Antiobesidade/administração & dosagem , Biópsia , Colite Isquêmica/diagnóstico , Colite Isquêmica/terapia , Feminino , Hidratação , Hemorragia Gastrointestinal/etiologia , Humanos , Injeções Subcutâneas , Sigmoidoscopia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
In this work, we estimate the inhibitory effect of two polysaccharides from Taraxacum officinale (TOP) on CCl(4)-induced oxidative stress and inflammation in Sprague-Dawley rats. TOP1 and 2 (304, 92 mg/kg bw) were administered for 7 days via a stomach sonde, and hepatitis was induced by a single dose of CCl(4) (50% CCl(4)/olive oil; 0.5 mL/kg bw) administration. CCl(4) significantly elevated serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. Histopathological observation further revealed that CCl(4)-induced moderate levels of inflammatory cell infiltration, centrilobular fatty change, apoptosis, and necrosis. However, TOPs pretreatment markedly decreased AST and ALT activities as well as hepatic lesions. TOPs also increased free radical scavenging activity, as exhibited by a lowered TBARS concentration. TOPs pretreatment also reversed other hepatitis-associated symptoms, including GSH depletion, inhibited anti-oxidative enzyme activities, up-regulation of NF-kappaB and increased expression of its regulatory inflammatory mediators, such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta. These results suggest that TOPs have a hepatoprotective effect by modulating inflammatory responses and ameliorating oxidative stress.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Sequestradores de Radicais Livres/farmacologia , Polissacarídeos/farmacologia , Taraxacum/química , Alanina Transaminase/sangue , Animais , Apoptose , Aspartato Aminotransferases/sangue , Tetracloreto de Carbono/toxicidade , Intoxicação por Tetracloreto de Carbono/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Glutationa/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , NF-kappa B/metabolismo , Necrose , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/antagonistas & inibidores , Oxirredutases/metabolismo , Extratos Vegetais/farmacologia , Ratos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
The subchronic inhalation toxicity of silver nanoparticles was studied in Sprague-Dawley rats. Eight-week-old rats, weighing approximately 253.2 g (males) and 162.6 g (females), were divided into four groups (10 rats in each group): fresh-air control, low dose (0.6 x 10(6) particle/cm(3), 49 microg/m(3)), middle dose (1.4 x 10(6) particle/cm(3), 133 microg/m(3)), and high dose (3.0 x 10(6) particle/cm(3), 515 microg/m(3)). The animals were exposed to silver nanoparticles (average diameter 18-19 nm) for 6 h/day, 5 days/week, for 13 weeks in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and pulmonary function tests were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and the organ weights were measured. Bile-duct hyperplasia in the liver increased dose dependently in both the male and female rats. Histopathological examinations indicated dose-dependent increases in lesions related to silver nanoparticle exposure, including mixed inflammatory cell infiltrate, chronic alveolar inflammation, and small granulomatous lesions. Target organs for silver nanoparticles were considered to be the lungs and liver in the male and female rats. No observable adverse effect level of 100 microg/m(3) is suggested from the experiments.
Assuntos
Exposição por Inalação/efeitos adversos , Nanopartículas/toxicidade , Prata/toxicidade , Animais , Análise Química do Sangue , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Agregação Eritrocítica/efeitos dos fármacos , Feminino , Testes de Função Renal , Pneumopatias/induzido quimicamente , Pneumopatias/patologia , Masculino , Nanopartículas/administração & dosagem , Tamanho do Órgão/efeitos dos fármacos , Tamanho da Partícula , Pneumonia/induzido quimicamente , Pneumonia/patologia , Ratos , Ratos Sprague-Dawley , Caracteres Sexuais , Prata/administração & dosagem , Prata/farmacocinéticaRESUMO
The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, and home products. However, while the population exposed to silver nanoparticles continues to increase with ever new applications, silver nanoparticles remain a controversial research area as regards their toxicity to biological systems. In particular, the oral toxicity of silver nanoparticles is of particular concern to ensure public and consumer health. Accordingly, this study tested the oral toxicity of silver nanoparticles (60 nm) over a period of 28 days in Sprague-Dawley rats following Organization for Economic Cooperation and Development (OECD) test guideline 407 with Good Laboratory Practice (GLP) application. Eight-week-old rats, weighing about 283 g for the males and 192 g for the females, were divided into four 4 groups (10 rats in each group): vehicle control, low-dose group (30 mg/kg), middle-dose group (300 mg/kg), and high-dose group (1000 mg/kg). After 28 days of exposure, the blood biochemistry and hematology were investigated, along with a histopathological examination and silver distribution study. The male and female rats did not show any significant changes in body weight relative to the doses of silver nanoparticles during the 28-day experiment. However, some significant dose-dependent changes were found in the alkaline phsophatase and cholesterol values in either the male or female rats, seeming to indicate that exposure to over more than 300 mg of silver nanoparticles may result in slight liver damage. There were no statistically significant differences in the micronucleated polychromatic erythrocytes (MN PCEs) or ratio of polychromatic erythrocytes among the total erythrocytes after silver nanoparticle exposure when compared with the control. Therefore, the present results suggest that silver nanoparticles do not induce genetic toxicity in male and female rat bone marrow in vivo. Nonetheless, the tissue distribution of silver nanopaticles did show a dose-dependent accumulation of silver content in all the tissues examined. In particular, a gender-related difference in the accumulation of silver was noted in the kidneys, with a twofold increase in the female kidneys when compared with the male kidneys.