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1.
Cancer Chemother Pharmacol ; 74(2): 309-22, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24916547

RESUMO

PURPOSE: 5-Fluorouracil (5-FU) is used for the treatment of colorectal cancer, but has low therapeutic response rate and severe side effects. Recently, fish oil (FO) rich in n-3 polyunsaturated fatty acids has been preferred to chemosensitize tumor cells to anticancer drugs. Therefore, the current study is designed to evaluate chemotherapeutic efficacy and toxicity profile of 5-FU in combination with FO in 1,2-dimethylhydrazine dihydrochloride/dextran sulfate sodium (DMH/DSS)-induced colon cancer model. METHODS: The therapeutic efficacy of 5-FU along with FO was analyzed through assessment of survival rate, tumor burden, volume, serum sialic acid levels, cytokeratin 19 (CK19) expression and index of cell proliferation such as cell cycle progression. Toxicological aspects were evaluated by standard functional and structural parameters related to spleen, gastrointestinal, liver and kidney. RESULTS: In the present study, 5-FU in combination with FO increased the survival rate in carcinogen-treated animals. Synergism of 5-FU and FO was also reflected in significant inhibition in tumor growth and serum sialic acid levels in DMH/DSS model. Moreover, the combination dosage significantly augmented the inhibition of cell cycle progression, as shown by CK19 expression. Additionally, FO ameliorated hematologic depression, gastrointestinal, hepatic and renal toxicity caused by 5-FU as substantiated by a marked improvement in structural and functional alterations of these organs. CONCLUSION: The supplementation of FO is potentially a promising option for increasing the therapeutic potential and mitigating the side effects of 5-FU.


Assuntos
1,2-Dimetilidrazina/toxicidade , Carcinógenos/toxicidade , Neoplasias do Colo/tratamento farmacológico , Sulfato de Dextrana/toxicidade , Suplementos Nutricionais , Óleos de Peixe/uso terapêutico , Fluoruracila/uso terapêutico , Animais , Antimetabólitos Antineoplásicos/uso terapêutico , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/patologia , Citometria de Fluxo , Testes de Função Renal , Testes de Função Hepática , Masculino , Camundongos , Camundongos Endogâmicos BALB C
2.
J Med Food ; 14(1-2): 147-55, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21138365

RESUMO

Acute necrotizing pancreatitis is characterized by focal macroscopic or diffuse necrosis, hemorrhage, and vascular thrombosis of the pancreas. Current treatment options are limited to supportive and symptomatic interventions. A large amount of experimental work is ongoing to identify novel therapeutic agents for acute pancreatitis. The present study was carried out to explore the beneficial effects of Emblica officinalis, a medicinal plant of India, on acute pancreatitis. Ascorbic acid is one of the major chemical components of E. officinalis, so a vitamin C group was included for comparison. Acute pancreatitis was induced by L-arginine. Rats were divided into the following groups: control (saline), arginine + saline, arginine + E. officinalis, and arginine + vitamin C. Animals in each group were sacrificed at 24 hours and 3, 14, and 28 days after pancreatitis induction for determination of biochemical parameters and histological examination. For rate of DNA synthesis and immunohistochemical studies, animals were sacrificed on Day 3 and Day 7. Drug administration was started 2 hours after the last arginine injection and continued until the day of sacrifice. E. officinalis treatment was found to be beneficial for treating acute pancreatitis. Serum levels of lipase and interleukin-10 were significantly lower than in the arginine group. Nucleic acid content, rate of DNA synthesis, pancreatic proteins, and pancreatic amylase content were significantly improved. Histopathological examination showed significantly lower total scores in the Emblica group. Vitamin C was found to be less efficacious than E. officinalis for all outcome parameters. Thus E. officinalis treatment was found to be beneficial in acute necrotizing pancreatitis.


Assuntos
Pancreatite Necrosante Aguda/tratamento farmacológico , Phyllanthus emblica/química , Extratos Vegetais/administração & dosagem , Amilases/sangue , Animais , Arginina/efeitos adversos , Modelos Animais de Doenças , Feminino , Humanos , Interleucina-10/sangue , Lipase/sangue , Masculino , Pancreatite Necrosante Aguda/sangue , Pancreatite Necrosante Aguda/induzido quimicamente , Pancreatite Necrosante Aguda/enzimologia , Ratos , Ratos Wistar
3.
Toxicol Sci ; 89(2): 547-53, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16280382

RESUMO

The present study was designed to evaluate the effects of long-term use of aqueous extract of gutkha (a form of smokeless tobacco) on the antioxidant defense status and histopathological changes in liver, lung, and kidney of male Wistar rats. Animals were orally administered aqueous extract of smokeless tobacco (AEST) at a low dose (96 mg/kg body weight per day) for 2 and 32 weeks, and at a high dose (960 mg/kg body weight per day) for 2 weeks. High-dose AEST for 2 weeks decreased the hepatic glutathione (GSH) and glutathione peroxidase (GPx), and increased lipid peroxidation (Lpx) by 17%, 19%, and 20%, respectively. Low-dose AEST for 32 weeks significantly decreased (p < 0.05) the antioxidant status in these organs. In liver, AEST decreased GSH levels and the activities of superoxide dismutase (SOD), catalase (CAT), and GPx by 34.6%, 29%, 17.1%, and 17.4%, respectively, but it increased Lpx by 64%. In kidney, GSH, SOD, CAT, and GPx were decreased by 26.6%, 23%, 33%, and 18%, respectively, with an increase of Lpx by 65%. AEST decreased the lung GSH, SOD, CAT, and GPx, and increased lung Lpx by 43%, 28.5%, 37%, 40%, and 24%, respectively. However, no change in the plasma levels of vitamins A, C, and E were observed with AEST treatment. Histopathological findings suggest that administration of AEST at the high dose for 2 weeks or at the low dose for 32 weeks could cause mild to moderate inflammation in liver and lungs. In conclusion, a decrease in the antioxidant defense system and long-term inflammation caused by smokeless tobacco may be risk factors for gutkha-induced pathogenesis.


Assuntos
Antioxidantes/metabolismo , Rim/enzimologia , Fígado/enzimologia , Pulmão/enzimologia , Tabaco sem Fumaça/toxicidade , Administração Oral , Animais , Catalase/metabolismo , Relação Dose-Resposta a Droga , Glutationa Peroxidase/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Extratos Vegetais/toxicidade , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Fatores de Tempo , Tabaco sem Fumaça/química , Vitaminas/sangue
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