RESUMO
BACKGROUND/OBJECTIVES: The apparent widespread extent of zinc (Zn) deficiency in developing countries and the efficacy of oral Zn supplements as an adjunct to oral rehydration therapy make oral Zn supplementation an increasingly important modality in clinical medicine and public health. In this study we aimed to compare the relative bioavailability of oral doses of 30 mg of Zn in two dosing forms. SUBJECTS/METHODS: In total, 10 healthy male volunteers ingested oral Zn doses with 200 ml plain water at about 0830 hours in the fasting state on two occasions, once as 30 mg of Zn in an aqueous solution of reagent grade zinc sulfate (ZnSO(4)) and another time as 1.5 NutriSet Zn tablets (Nutriset, Malaunay, France); on a third occasion, only plain water was consumed. Venous blood specimens were collected at baseline, 60, 120, 180 and 240 min after ingestion and the plasma Zn was measured for each sample. RESULTS: The relative bioavailability of oral Zn from a commonly used, tableted (NutriSet) form is only about half of that of a reference dose of aqueous ZnSO(4) as indicated by the area under the curve of serial plasma Zn excursion and maximal change in circulating Zn. CONCLUSIONS: Reduced or absent functional outcomes in Zn intervention trials may derive, in part, from a lower than anticipated intestinal uptake of the Zn in the tableted form.
Assuntos
Suplementos Nutricionais , Sulfato de Zinco/administração & dosagem , Sulfato de Zinco/farmacocinética , Zinco/administração & dosagem , Zinco/farmacocinética , Administração Oral , Adolescente , Adulto , Disponibilidade Biológica , Países em Desenvolvimento , Relação Dose-Resposta a Droga , Jejum , Guatemala , Humanos , Masculino , Pessoa de Meia-Idade , Comprimidos/administração & dosagem , Adulto Jovem , Zinco/sangueRESUMO
BACKGROUND: We have evidence for enterohepatic cycling of bilirubin experimentally and in vivo in humans. This study was designed to investigate whether Zn salts might inhibit such cycling of bilirubin. MATERIALS AND METHODS: Micellar bile salt solutions with unconjugated bilirubin were prepared, appropriate concentrations of Zn salts were added, and unconjugated bilirubin precipitation was measured. Hamsters and Wistar rats were fed a chow diet or a chow diet enriched with 1% ZnSO4, and bilirubin secretion rates were monitored. RESULTS: Unconjugated bilirubin was precipitated maximally (90%) after a 10-min incubation with 5 mM Zn salts in the pH range of 6.8-9.0. In control hamsters, total bilirubin secretion rates into bile were 36.0 +/- 2.8 nmol h(-1) 100g(-1) body weight, whereas they were 25.0 +/- 3.3 nmol h-1 100(-1) g in the ZnSO4 group (P < 0.05). CONCLUSIONS: Zn salts that flocculate at physiological pH adsorb unconjugated bilirubin almost completely from unsaturated micellar BS solutions. In addition, Zn salts administered orally suppress biliary bilirubin secretion rates in hamsters. These findings suggest that the administration of Zn salts may inhibit the enterohepatic cycling of unconjugated bilirubin in humans who are predisposed to pigment gallstone formation due to diet, disease or drugs.
Assuntos
Bilirrubina/metabolismo , Fígado/metabolismo , Sulfato de Zinco/farmacocinética , Animais , Ácidos e Sais Biliares/química , Ácidos e Sais Biliares/farmacologia , Fístula Biliar/metabolismo , Bilirrubina/química , Carbonatos/química , Carbonatos/farmacologia , Precipitação Química , Colelitíase/metabolismo , Cricetinae , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Masculino , Mesocricetus , Ratos , Ratos Wistar , Acetato de Zinco/química , Acetato de Zinco/farmacologia , Compostos de Zinco/química , Compostos de Zinco/farmacologia , Sulfato de Zinco/químicaRESUMO
Food fortification with a proper zinc compound is an economic and effective strategy to prevent zinc deficiency. BioZn-AAS, a zinc gluconate stabilized with glycine, was compared with zinc sulfate (reference standard), zinc hydroxide, and zinc gluconate, all of them labeled with (65)Zn. This preclinical study was performed on Sprague-Dawley rats of both sexes, and the administered dose was 85 microg/kg of zinc. Bioavailability studies showed that absorption of BioZn-AAS was not statistically different than absorption from other sources in female rats (25.65% +/- 2.20% for BioZn-AAS, 28.24% +/- 4. 60% for ZnSO(4), 24.91% +/- 4.02% for Zn[OH](2), and 25.51% +/- 2. 70% for Zn-gluconate). In the case of the male rats, absorption of BioZn-AAS (27.97% +/- 4.20%) was higher (P<0.05) than that from the other compounds (23.15% +/- 2.90% for ZnSO(4), 22.62% +/- 3.90% for Zn[OH](2), and 22.30% +/- 3.90% for Zn-gluconate). Biodistribution studies demonstrated that the zinc from BioZn-AAS followed the same metabolic pathway as zinc from the other sources. Toxicity studies were performed with 50 female and 50 male rats. The value of oral lethal dose 50 (LD(50)) was 2000 mg/kg for female rats and 1900 mg/kg for male rats. Therefore, we conclude that BioZn-AAS has adequate properties to be considered a proper zinc compound for food fortification or dietary supplementation.