RESUMEN
The use of in vivo models to assess nephrotoxicity has faced ethical limitations. A viable alternative is the ex vivo model that combines the 3 R principles with the preservation of tissue histology. Here, we established a gentamicin nephrotoxicity model using pigs` kidney explants and investigated the effect of phytic acid (IP6) against gentamicin- induced nephrotoxicity. A total of 360 kidney explants were divided into control, gentamicin (10 mM), IP6 (5 mM), and gentamicin+IP6 groups. The activity of gammaglutamyltransferase (GGT), creatinine levels, histological assessment, oxidative stress, and inflammatory cytokine expression were analyzed. Exposure to gentamicin induced an increase in GGT activity, creatinine levels, lesion score, lipoperoxidation and IL-8 expression. Explants exposed to IP6 remained like the control. The addition of IP6 to gentamicin prevented tissue damage, increasing the antioxidant status and gene expression of IL-10. This model proved to be an adequate experimental approach for identifying nephrotoxins and potential products to modulate the toxicity.
Asunto(s)
Enfermedades Renales , Insuficiencia Renal , Animales , Porcinos , Ácido Fítico/farmacología , Ácido Fítico/uso terapéutico , Ácido Fítico/metabolismo , Creatinina , Riñón , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/metabolismo , Gentamicinas/toxicidad , Estrés Oxidativo , Enfermedades Renales/patologíaRESUMEN
Inositol hexakisphosphate (IP6) and inositol both regulate insulin secretion, but their combined use in the management of diabetes deserves investigation. The combined effects of IP6 and inositol supplementation were investigated in streptozotocin-induced type 2 diabetic rats. The following groups of rats were studied for 8 weeks: non-diabetic control, non-diabetic high-fat diet control, diabetic untreated, diabetic rats treated with the combination of IP6 and inositol (650 mg/kg bw) and diabetic rats treated with glibenclamide (10 mg/kg bw). High-fat diet and streptozotocin were used to induce type 2 diabetes mellitus in Sprague-Dawley rats. Body weight, blood glucose, glycated haemoglobin, insulin, serum leptin, HOMA-insulin resistance scores, intestinal amylase activity, serum and faecal lipids and food and fluid consumption were measured. Treatment with the combination significantly reduced blood glucose (306 ± 53 mg/dl) and insulin resistance score (1.93 ± 0.45) compared with diabetic controls (522 ± 24 mg/dl and 5.1 ± 0.69 respectively). Serum leptin (2.8 ± 0.6 ng/dl) and faecal triglycerides (108 ± 8 mg/dl) were significantly increased in rats treated with the combination compared with the diabetic control (1.8 ± 0.06 ng/dl and 86 ± 4 mg/dl). Serum triglyceride (47 ± 5.1 mg/dl), total cholesterol (98 ± 3.2 mg/dl) and food intake (26 ± 0.3 g) were significantly reduced by 45%, 25% and 25%, respectively, in rats treated with the combination compared with the diabetic control. Inositol and IP6 combined supplementation may be effective in the management of type 2 diabetes mellitus and related metabolic disorders by regulating some aspects of lipid and carbohydrate metabolism.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Inositol/uso terapéutico , Ácido Fítico/uso terapéutico , Amilasas/metabolismo , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/fisiopatología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Suplementos Dietéticos , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Líquidos/fisiología , Evaluación Preclínica de Medicamentos/métodos , Quimioterapia Combinada , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/fisiología , Heces/química , Hipoglucemiantes/farmacología , Inositol/farmacología , Intestinos/enzimología , Leptina/sangre , Metabolismo de los Lípidos/efectos de los fármacos , Lípidos/sangre , Masculino , Ácido Fítico/farmacología , Ratas Sprague-DawleyRESUMEN
Both phytic acid (PA) and catechin (CA) are well known antioxidants of natural origin. They were frequently tried on experimental level as hepatoprotectants, relying only on their antioxidant properties. The present study was conducted mainly to outline the other biochemical pathways underlying the hepatotherapeutic potential of both drugs and to check a possible synergistic action if prescribed concomitantly. As both materials are frequently taken on a daily basis in food and drinks, it will be helpful to pursue their possible utility and/or to check if their value is really of medical importance. For this purpose, CCl(4) was used as a hepatotoxin, we evaluated plasma total sialic acid (TSA), serum ascorbic acid (AA) levels, liver tissue thiobarbituric acid reactive species (TBARS) as a marker for lipid peroxidation and total protein (TP) content as a rough marker to measure hepatic synthetic capability in 80 male Wistar rats as experimental models. Animals were classified into 8 groups (10 rats each), the first as control, the second as PA treated (0.3 mg kg (-1)), orally, the third as CA treated (30 mg kg (-1)) intraperitoneally, the fourth given both drugs, as a single daily dose for 2 weeks. The same design was repeated 24 hours after CCl(4)-intoxication (1mL kg (-1)), intraperitoneally, as a single dose. The results revealed that both PA and CA when used individually, significantly down-regulated TSA in both physiologic (no CCl(4 )treatment) and pathologic (CCl(4)- intoxication) states accompanied by significant decrease in lipoperoxidation. The therapeutic action against TSA and the antioxidant power were abolished by co-administration of both drugs . AA was only decreased by PA and the combination in the physiologic state. Both PA and CA showed significant therapeutic effect for protein synthesis against CCl(4)-intoxication, but the combination abolished this effect. We conclude that both drugs can be considered as a chemotherapeutic against hepatopathies and we for the first time contraindicate the concomitant use of both drugs.
Asunto(s)
Tetracloruro de Carbono/toxicidad , Catequina/uso terapéutico , Hepatopatías/tratamiento farmacológico , Ácido Fítico/uso terapéutico , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Animales , Antioxidantes/uso terapéutico , Ácido Ascórbico/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas , Hígado/metabolismo , Hepatopatías/sangre , Masculino , Ácido N-Acetilneuramínico/sangre , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
Phytate [myo-inositol (1,2,3,4,5,6) hexakisphosphate], a naturally compound formed during maturation of plant seeds and grains, is a common constituent of plant-derived foods. The major concern about the presence of phytate in thediet is its negative effect on mineral uptake. Minerals of concern in this regardin clude Zn2+, Fe2+/3+, Ca2+, Mg2+, Mn2+, and Cu2+. Especially zinc and iron deficiencies were reported as a consequence of high phytate intakes. In addition, a negative effect on the nutritional value of protein by dietary phytate is discussed. Consumption of phytate, however, seems not to have only negative effects on human health. Dietary phytate was reported to prevent kidney stone formation, protect against diabetes mellitus, caries, atherosclerosis and coronary heart disease as well as against a variety of cancers. Furthermore, individual myo-inositol phosphate esters have been proposed to be metabolicall y active. D-myo-inositol(1,2,6)trisphosphate, for example, has been studied in respect to prevention of diabetes complications and treatment of chronic inflammations as well as cardiovascular diseases and due to its antiangiogenic and antitumour effects myo-inositol(1,3,4,5,6) pentakisphosphate was suggested as a promising compound for anticancer therapeutic strategies
El fitato, (1,2,3,4,5,6) hexafosfato de mio-inositol, compuesto que se forma naturalmente durante la maduración de las semillas ygranos, es un constituyente común de los alimentos vegetales. La mayor preocupación con la presencia de fitato es su efecto negativo en la absorción de minerales, particularmente Zn2+, Fe2+/3+, Ca2+, Mg2+, Mn2+, e Cu2+.Las deficiencias de zinc y hierro, fueron relacionadas con altas ingestas de fitato. Es discutido también su efecto negativo en el valor biológico de las proteínas. Sin embargo, el consumo de fitato parece no tener solamente efectos negativos para la salud humana. Fue descripto, por ejemplo, un efecto protector del fitato contra la formación de cálculos renales, contra la diabetes mellitus, formación de caries, ateriosclerosis y enfermedades coronarias, como también contra una gran variedad de tipos de tumores malignos. Además, ha sido propuesto que, individualmente, algunos ésteres de fosfato de mio-inositol sean metabólicamente activos. Hay estudios relacionando el (1,2,6) trisfosfato de D-mio-inositol con la prevención de complicaciones de la diabetes y con el tratamiento de inflamaciones crónicas y de enfermedades cardiovasculares; el (1,3,4,5,6)pentafosfato de mio-inositol, debido a sus efectosanti-angiogénicos y anti-tumorales, fue sugerido como un compuesto promisor en las estratégias terapéuticas contra el cáncer
O fitato, (1,2,3,4,5,6) hexafosfato de mio-inositol], composto que ocorre naturalmente e é formado durante a maturação de sementes e grãos, é um constituinte comum de alimentos vegetais. A maior preocupação com a presença de fitato na dieta é seu efeito negativo na absorção de minerais, particularmente Zn2+, Fe2+/3+, Ca2+, Mg2+, Mn2+, e Cu2+. As deficiências de zinco e de ferro, em especial, foram relacionadas com altas ingestões de fitato. É discutido, também, o efeito negativo do fitato no valor biológico de proteínas. Por outro lado, o consumo de fitato parece não ter somente efeitos negativos para a saúde humana. Foi descrito, por exemplo, um efeito protetor do fitato contra a formação de cálculos renais, contra diabetes Mellitus, formação de cáries, aterosclerose e doença coronariana, bem como contra uma grande variedade de tipos de tumores malignos. Além disso, foi proposto que, individualmente, alguns ésteres de fosfato de mio-inositol sejam metabolicamente ativos. Assim, há estudos relacionando o (1,2,6) trisfosfato de D-mio-inositol com a prevenção das complicações do diabetes e com o tratamento de inflamações crônicas e de doenças cardiovasculares; o(1,3,4,5,6) pentafosfato de mio-inositol, devido a seus efeitos anti-angiogênicos e anti-tumorais, foi sugerido como um composto promissor nas estratégias terapêuticas contra o câncer
Asunto(s)
Ácido Fítico/efectos adversos , Ácido Fítico/metabolismo , Ácido Fítico/uso terapéuticoRESUMEN
PURPOSE: To evaluate modulation in the expression of Transforming growth factor beta2 (TGF-beta2) in short-term colon carcinogenesis. METHODS: 64 male rats was used, comprising 4 groups of 16 animals each: group 1 received Inositol hexaphosphate (IP6) and azoxymethane (AOM); group 2, AOM alone; group 3, IP6 alone; group 4 was used as control. Groups 1 and 3 were given 1% IP6 in drinking water for 6 weeks. AOM was administered subcutaneously at weeks 3 and 4 of the experiment at 20 mg/kg of body weight each week. Immunohistochemical processing was performed with the use of anti-TGF-beta2 primary antibodies in right colon samples and quantitation of TGF-beta2 as percentage of expression, through computer-assisted image processing. RESULTS: mean values of TGF-beta2 expression were 9.0 +/- 3.9% for group 4 (control), 12.7 +/- 4.0% for group 3 (IP6), 19.3 +/- 6.2% for group 2 (AOM), and 13.1 +/- 5.3% for group 1 (IP6+AOM). The value of p was calculated as 0.0001 for a 5% or lower significance level. CONCLUSION: the experiment revealed a significant increase in TGF-beta2 expression in right colon with the administration of AOM, and a significant decrease in TGF-beta2 expression when IP6 was administered with AOM.
Asunto(s)
Colon/efectos de los fármacos , Neoplasias del Colon/prevención & control , Ácido Fítico/uso terapéutico , Factor de Crecimiento Transformador beta2/efectos de los fármacos , Animales , Azoximetano , Pruebas de Carcinogenicidad , Carcinógenos , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/metabolismo , Modelos Animales de Enfermedad , Procesamiento de Imagen Asistido por Computador , Masculino , Ratas , Factor de Crecimiento Transformador beta2/metabolismoRESUMEN
PURPOSE: To evaluate modulation in the expression of Transforming growth factor beta2 (TGF-beta2) in short-term colon carcinogenesis. METHODS: 64 male rats was used, comprising 4 groups of 16 animals each: group 1 received Inositol hexaphosphate (IP6) and azoxymethane (AOM); group 2, AOM alone; group 3, IP6 alone; group 4 was used as control. Groups 1 and 3 were given 1 percent IP6 in drinking water for 6 weeks. AOM was administered subcutaneously at weeks 3 and 4 of the experiment at 20 mg/kg of body weight each week. Immunohistochemical processing was performed with the use of anti-TGF-beta2 primary antibodies in right colon samples and quantitation of TGF-beta2 as percentage of expression, through computer-assisted image processing. RESULTS: mean values of TGF-beta2 expression were 9.0 ± 3.9 percent for group 4 (control), 12.7 ± 4.0 percent for group 3 (IP6), 19.3 ± 6.2 percent for group 2 (AOM), and 13.1 ± 5.3 percent for group 1 (IP6+AOM). The value of p was calculated as 0.0001 for a 5 percent or lower significance level. CONCLUSION: the experiment revealed a significant increase in TGF-beta2 expression in right colon with the administration of AOM, and a significant decrease in TGF-beta2 expression when IP6 was administered with AOM.
OBJETIVO: Avaliar a modulação da expressão do TGF-beta2 na carcinogênese colônica de curta duração em colon direito de ratos. Método: foram utilizados 64 ratos Wistar, machos divididos em 4 grupos de 16 animais. Grupo 1: recebeu Inositol hexafosfato (IP6) e azoximetano (AOM). Grupo 2 recebeu somente AOM. Grupo 3: recebeu somente IP6. Grupo 4: grupo de controle não recebeu nem IP6 nem AOM. O azoximetano (AOM) foi ministrado na dose 20mg/kg, por via subcutânea na 3ª e 4ª semanas do experimento. Foi realizada imunoistoquímica utilizando-se anticorpo primário TGFbeta2. Utilizou-se processamento de imagem computadorizada para quantificação da expressão do TGFbeta2. RESULTADOS: a média da expressão do TGFbeta2 foi de 9.0 ± 3.9 por cento para o grupo 4 (controle), 12.7 ± 4.0 por cento para o grupo 3 (IP6), 19.3 ± 6.2 por cento para o grupo 2 (AOM), e 13.1 ± 5.3 por cento para o grupo 1 (IP6+AOM). CONCLUSÃO: ocorreu aumento significante a da expressão de TGF-beta2 no cólon, com a administração de AOM, e uma diminuição significante na expressão de TGF-beta2 quando IP6 IP6 foi administrado com AOM.