RESUMO
This study was conducted to investigate the role of curcumin and zinc on the biokinetics and biodistribution of (65)Zn during colon carcinogenesis. Male wistar rats were divided into five groups, namely normal control, 1,2-dimethylhydrazine (DMH) treated, DMH + curcumin treated, DMH + zinc treated, and DMH + curcumin + zinc treated. Weekly subcutaneous injections of DMH (30 mg/kg body weight) for 16 weeks initiated colon carcinogenesis. Curcumin (100 mg/kg body weight orally) and ZnSO4 (227 mg/L in drinking water) were supplemented for 16 weeks. This study revealed a significant depression in the fast (Tb1) and slow component (Tb2) of biological half-life of (65)Zn in the whole body of DMH-treated rats, whereas liver showed a significant elevation in these components. Further, DMH treatment showed a significant increase in the uptake values of (65)Zn in colon, small intestine, and kidneys. Subcellular distribution depicted a significant increase in (65)Zn uptake values in mitochondrial, microsomal, and postmicrosomal fractions of colon. However, curcumin and zinc supplementation when given separately or in combination reversed the trends and restored the uptake values close to normal range. Our study concludes that curcumin and zinc supplementation during colon carcinogenesis shall prove to be efficacious in regulating the altered zinc metabolism.
Assuntos
Neoplasias do Colo/metabolismo , Curcumina/farmacologia , Radioisótopos de Zinco/farmacocinética , Zinco/farmacologia , 1,2-Dimetilidrazina , Animais , Carcinogênese , Carcinógenos , Masculino , Ratos , Ratos WistarRESUMO
Diabetes is a life threatening disease and its onset is linked with both environmental and genetic factors. Zinc metabolism gets altered during diabetes and results in many complications. The present study was designed to elucidate the effects of zinc supplementation on the biokinetics of (65)Zn in whole body, liver and its biodistribution in diabetic rats. The animals were divided into four groups viz; normal control; diabetic (single intraperitoneal injection of alloxan 150 mg/kg body weight); zinc treated (227 mg/l in drinking water); and diabetic + zinc treated. To carry out biokinetics study, each rat was injected intraperitoneally with 0.74 MBq radioactivity of (65)Zn following 4 weeks of different treatments and the radioactivity was determined by using a suitably shielded scintillation counter. Alloxan induced diabetic rats showed a significant decrease in both the fast (Tb(1)) and slow (Tb(2)) components of biological half-life of (65)Zn which, however, were normalized in whole body (P > 0.05) following zinc supplementation. In case of liver, Tb(2) component was brought back to the normal but Tb(1) component was not increased significantly. The present study indicates that the paucity of zinc in the tissues of the diabetic animals was due to decreased retention of tissue zinc as evidenced by increased serum Zn, hyperzincuria and increased rate of uptake of (65)Zn by the liver. Zinc supplementation caused a significant improvement in the retention of zinc in the tissues and is therefore likely to be of benefit in the treatment of diabetes.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Suplementos Nutricionais , Fígado/efeitos dos fármacos , Fígado/metabolismo , Radioisótopos de Zinco/farmacocinética , Zinco/administração & dosagem , Zinco/farmacologia , Animais , Humanos , Masculino , Ratos , Ratos Wistar , Distribuição TecidualRESUMO
The present study was conducted to evaluate the kinetics of zinc utilization during the formation of colon carcinoma in an animal model of colon carcinogenesis. The rats were segregated into 4 groups: untreated control, 1,2-dimethylhydrazine (DMH) treated, zinc treated, and DMH+zinc treated. Colon carcinogenesis was initiated through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 8 wk. Zinc (in the form of zinc sulphate) was supplemented at a dose level of 227 mg/L in drinking water, ad libitum for the entire duration of study. Whole body (65)Zn kinetics followed two-compartment kinetics, with Tb(1) representing the initial fast component of the biological half-life and Tb(2), the slower component. The Tb(1) component showed a significant elevation while the Tb(2) component was significantly diminished in DMH-treated rats, which, however, got normalized following zinc supplementation. The biodistribution and subcellular distribution of (65)Zn was significantly affected in DMH-treated rats when compared to normal control rats. However, zinc significantly reversed the altered (65)Zn uptake in different organs and various fractions of colon. The present study for the first time demonstrated a faster mobilization of zinc during initiation of experimentally induced colon carcinoma and provides a physiological basis for the role of zinc in colon tumorigenesis.
Assuntos
Neoplasias do Colo/induzido quimicamente , Suplementos Nutricionais , Sulfato de Zinco/administração & dosagem , Sulfato de Zinco/farmacocinética , 1,2-Dimetilidrazina/toxicidade , Animais , Carcinógenos/toxicidade , Colo/patologia , Meia-Vida , Masculino , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual , Radioisótopos de Zinco/farmacocinéticaRESUMO
The effect of red wine (RW), red grape juice (RGJ), green tea (GT), and representative polyphenols on Caco-2 cell (65)Zn uptake was explored. RW, RGJ, and GT enhanced the uptake of zinc from rice matrix. Fractionation of RW revealed that enhancing activity of zinc uptake was exclusively resided in the polyphenol fraction. Among the polyphenols tested, only tannic acid and quercitin stimulated the uptake of zinc while others did not influence the uptake. In tune with these results, only tannic acid and quercitin competed with zinquin (a zinc selective fluorophore) for zinc in vitro. Although all the polyphenols tested appear to enhance the expression of metallothionein (MT), the induction was higher with tannic acid, quercitin, and RW extract. Furthermore, phytic acid abrogated the tannic acid-induced MT expression. These results suggest that polyphenol-rich beverages, tannic acid, and quercitin bind and stimulate the zinc uptake and MT expression in Caco-2 cells.
Assuntos
Absorção/efeitos dos fármacos , Bebidas/análise , Flavonoides/análise , Flavonoides/farmacologia , Metalotioneína/metabolismo , Fenóis/análise , Fenóis/farmacologia , Regulação para Cima/efeitos dos fármacos , Zinco/farmacocinética , Ligação Competitiva , Células CACO-2 , Quelantes/química , Digestão , Flavonoides/química , Flavonoides/isolamento & purificação , Frutas/química , Humanos , Oryza/química , Oryza/metabolismo , Fenóis/química , Fenóis/isolamento & purificação , Ácido Fítico/análise , Ácido Fítico/farmacologia , Polifenóis , Quercetina/química , Quercetina/farmacologia , Quinolonas/química , Sementes/química , Sementes/metabolismo , Taninos/análise , Taninos/antagonistas & inibidores , Taninos/química , Taninos/farmacologia , Chá/química , Compostos de Tosil/química , Vitis/química , Vinho/análise , Zinco/análise , Zinco/química , Radioisótopos de Zinco/farmacocinéticaRESUMO
Dietary factors are considered crucial for the prevention of initiating events in the multistep progression of colon carcinoma. There is substantial evidence that zinc may play a pivotal role in host defense against several malignancies, including colon cancer. The present study was conducted to evaluate the kinetics of (65)Zn utilization following experimental colon carcinogenesis in rat model. Twenty rats were segregated into two groups viz., untreated control and dimethylhydrazine (DMH) treated. Colon carcinogenesis was established through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 16 weeks. Whole body (65)Zn kinetics followed two compartment kinetics, with Tb(1) representing the initial fast component of the biological half-life and Tb(2), the slower component. The present study revealed a significant depression in the Tb(1) and Tb(2) components of (65)Zn in DMH treated rats. Further, DMH treatment caused a significant increase in the percent uptake values of (65)Zn in the colon, small intestine, kidney and blood, whereas a significant decrease was observed in the liver. Subcellular distribution revealed a significant increase in (65)Zn uptake in the mitochondrial and microsomal fractions following 16 weeks of DMH supplementation. In conclusion, the present study demonstrated a slow mobilization of (65)Zn during promotion of experimentally induced colon carcinogenesis and provides a physiological basis for the role of (65)Zn in colon tumorigenesis, which may have clinical implications in the management of colon cancer.
Assuntos
Carcinógenos/toxicidade , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/metabolismo , Dimetilidrazinas/toxicidade , Animais , Biomarcadores Tumorais/metabolismo , Peso Corporal/efeitos dos fármacos , Neoplasias do Colo/patologia , Neoplasias do Colo/fisiopatologia , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Radioisótopos de Zinco/metabolismo , Radioisótopos de Zinco/farmacocinéticaRESUMO
AIM: To evaluate the effects of zinc on the biokinetics of (65)Zn in rat and its distribution in various organs and in subcellular compartment following lithium therapy. METHODS: Female wistar rats received either lithium treatment at a dose of 1.1g/kg in diet, zinc alone at a dose of 227 mg/L in drinking water, and combined lithium plus zinc for duration of four months. RESULTS: After four months of lithium treatment, liver enzymes increased significantly (glutamic oxaloacetic transaminase, +66.73%; glutamic pyruvic transaminase, +63.70%; alkaline phosphatase, +40.28%; p< or =0.001); zinc supplementation to lithium-treated rats significantly reduced liver enzymes (glutamic oxaloacetic transaminase, -13.11%; glutamic pyruvic transaminase, -21.78%; alkaline phosphatase, -11.77%; p< or =0.001). The biological half-lives of (65)Zn showed an initial fast component (Tb(1)) and a slower component (Tb(2)). A significant increase in Tb(2) (38.82%, p< or =0.001) in liver was observed following lithium treatment, which significantly decreased following zinc treatment (21.71%, p< or =0.001). A significant decrease in the uptake of (65)Zn (53.93%, p< or =0.01) in liver was observed and in nuclear (p< or =0.01), mitochondrial (p< or =0.01), and microsomal (52.67%, p< or =0.001) fractions. A significant increase in the uptake of (65)Zn (82.92%, p< or =0.05) in liver microsomal fraction (34.09%, p< or =0.001) was observed in lithium-treated rats receiving zinc supplementation. CONCLUSION: The study suggests that zinc has the potential to regulate the biokinetics of (65)Zn and its subcellular distribution in rat liver following lithium therapy.
Assuntos
Transporte Biológico/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Lítio/farmacologia , Fígado/metabolismo , Radioisótopos de Zinco/farmacocinética , Zinco/farmacologia , Alanina Transaminase/efeitos dos fármacos , Alanina Transaminase/metabolismo , Fosfatase Alcalina/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Aspartato Aminotransferases/efeitos dos fármacos , Aspartato Aminotransferases/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Feminino , Fígado/efeitos dos fármacos , Fígado/patologia , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Ratos , Ratos WistarRESUMO
Whole body counting studies of 65Zn indicated that the Tb1 (the faster component) was significantly decreased while the slower component (Tb2) was increased significantly following ethanol treatment. Interestingly, following zinc treatment to ethanol treated rats, slower component (Tb2) of 65Zn came back to within normal limits while the faster component (Tb1) got significantly elevated in comparison to ethanol treatment. Percent uptake values of 65Zn were found to be increased in liver, intestine, muscle, brain and kidney, and decreased in bone under alcoholic conditions. Interestingly, the uptake values of 65Zn in all the organs except muscle were reverted back to within normal limits upon zinc supplementation to these ethanol intoxicated animals. A significant decrease in zinc contents was noticed in ethanol treated rats, which, however, were raised to normal levels upon zinc supplementation: Copper levels, on the other hand, were significantly enhanced in both ethanol fed and combined ethanol + zinc treated rats. Calcium levels were significantly decreased in both ethanol and zinc treated rats, which however were further reduced upon zinc supplementation to ethanol fed rats. However, no significant change was observed in the concentrations of sodium and potassium in any of the treatment groups. In conclusion, zinc appears to play a protective role by normalizing the turnover of 65Zn in whole body as well as in its uptake in different organs under alcoholic conditions.
Assuntos
Etanol/farmacologia , Fígado/metabolismo , Oligoelementos/metabolismo , Radioisótopos de Zinco/farmacocinética , Zinco/farmacocinética , Animais , Sítios de Ligação , Cálcio/metabolismo , Suplementos Nutricionais , Masculino , Ratos , Ratos Wistar , Fatores de Tempo , Distribuição Tecidual , Zinco/metabolismo , Radioisótopos de Zinco/metabolismoRESUMO
Interference of three dominant weed extracts viz., Ageratum conyzoides L., Melilotus indica All. and Parthenium hysterophorus L. were examined on seed germination, seedling growth, and nutrient uptake (32P and 65Zn) in three different varieties (PD-10, PD-12 and PB) of paddy (Oryza sativa L.). Among the three different varieties irrespective of weed extracts, PD-10 and PD-12 were resistant and PB was susceptible in terms of seed germination, radicle length and plumule dry weight; and PD-12 and PB were resistant and susceptible, respectively, in terms of plumule length and total seedling dry weight. A. conyzoides caused maximum reduction in seed germination and M. indica in seedling growth in different varieties of paddy. The weed extracts interfered in uptake of both 32P and 65Zn and there was a gradual decrease in uptake of both nutrients with increasing concentration of extracts in both root and shoot. The uptake of 32P and 65Zn was more inhibitory with the extracts of A. conyzoides and M. indica, respectively in different varieties. The inhibition in seed germination, seedling growth and nutrient uptake may be due to the presence of phenolics and other secondary metabolities. The phenolics such as gallic, vanillic, protocatechuic and p-hydroxybenzoic acids were identified from these weed extracts.
Assuntos
Asteraceae/química , Melilotus/química , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Extratos Vegetais/farmacologia , Análise de Variância , Cromatografia Líquida de Alta Pressão , Germinação/efeitos dos fármacos , Índia , Oryza/efeitos dos fármacos , Fenóis/análise , Radioisótopos de Fósforo/farmacocinética , Extratos Vegetais/química , Contagem de Cintilação , Especificidade da Espécie , Radioisótopos de Zinco/farmacocinéticaRESUMO
The effects on the absorption of 65Zn by two varieties of raw faba bean (Vicia faba L., minor) or seed components that may interfere with mineral metabolism in the gut, have been studied in growing rats. In bean diets all protein was supplied by the meals, and the fractions were tested by incorporating them in control diet at the same levels as they occur in the seeds. Absorption of 65Zn was also measured in rats fed dephytinized bean meal produced by including phytase in the diet. Rats were pair-fed diets supplemented with amino acids and minerals to target requirements and containing 40 mg Zn/kg diet. True absorption of Zn was 50-70% lower in rats fed diets containing both cultivars of faba bean meals than in those fed the control diet. Although soluble nonstarch polysaccharides caused a significant reduction in the absorption of Zn, this effect disappeared after the removal of phytate by demineralization. In contrast, despite its negligible content of phytate, the insoluble nonstarch polysaccharides in the cell wall fraction of the cotyledon accounted for most of the reduction in Zn absorption in rats fed the faba bean diets. Addition of phytic acid to the control diet significantly reduced the absorption of 65Zn but only from 44 to 36%. Moreover, the increase in the absorption of Zn was similarly small, from 21% to 29%, with the addition of phytase to the faba bean diet.(ABSTRACT TRUNCATED AT 250 WORDS)