Suppression of CFTR-mediated Cl- Secretion of Airway Epithelium in Vitamin C-deficient Mice

Hyperoxic ventilation induces detrimental effects on the respiratory system, and ambient oxygen may be harmful unless compensated by physiological anti-oxidants, such as vitamin C. Here we investigate the changes in electrolyte transport of airway epithelium in mice exposed to normobaric hyperoxia and in gulonolacton oxidase knock-out (gulo[-/-]) mice without vitamin C (Vit-C) supplementation. Short-circuit current (Isc) of tracheal epithelium was measured using Ussing chamber technique. After confirming amiloride-sensitive Na+ absorption (DeltaIsc,amil), cAMP-dependent Cl- secretion (DeltaIsc,forsk) was induced by forskolin. To evaluate Ca2+-dependent Cl- secretion, ATP was applied to the luminal side (DeltaIsc,ATP). In mice exposed to 98% PO2 for 36 hr, DeltaIsc,forsk decreased, DeltaIsc,amil and DeltaIsc,ATP was not affected. In gulo(-/-) mice, both DeltaIsc,forsk and DeltaIsc,ATP decreased from three weeks after Vit-C deprivation, while both were unchanged with Vit-C supplementation. At the fourth week, tissue resistance and all electrolyte transport activities were decreased. An immunofluorescence study showed that the expression of cystic fibrosis conductance regulator (CFTR) was decreased in gulo(-/-) mice, whereas the expression of KCNQ1 K+ channel was preserved. Taken together, the CFTR-mediated Cl- secretion of airway epithelium is susceptible to oxidative stress, which suggests that supplementation of the antioxidant might be beneficial for the maintenance of airway surface liquid.

Correlacao entre hipercolesterolemia e dieta deficiente em vitamina C / Correlation between hypercholesterolemia and vitamin C deficient diet

A carencia de vitamina C interfere tanto na atividade da enzima lecitina colesterol acil-transferase como na transformacao do colesterol em seu principal catabolico: os acidos biliares. Tem-se observado ainda, a presenca de varicosidade da veia sublingual em individuos com hipovitaminose C. Selecionamos quinze pacientes com niveis sanguineos de colesterol normais e quinze pacientes hipercolesterolemicos para estudar a correlacao entre a hipercolesterolemia e a deficiencia de ingestao de vitamina C. Realizamos analise estatistica com teste "t" de Student e teste tipo Caso-Controle, obtendo os seguintes dados: (1) Quanto ao nivel de colesterol, os dois grupos apresentaram diferenca significativa, no grupo hipercolesterolemicos com niveis de 422 ñ 116,2018 mg/100 ml e no grupo normocolesterolemicos 160,73 ñ 29,5356 mg/100 ml. (2) A media diaria de vitamina C na dieta e significativamente maior no grupo normocolesterolemico (170,33 ñ 75,18 mg) do que no grupo hipercolesterolemico (39,01 ñ 25,89 mg). (3) O grupo hipercolesterolemico apresenta uma media de ingestao diaria maior do colesterol do que o grupo normocolesterolemico, porem nao ha significancia estatistica. (4) O grupo hipercolesterolemico demonstra a ocorrencia maior de varicosidade sublingual estatisticamente significante em treze casos enquanto que no...

Effect of vitamin C deficiency and excess on the liver: a histopathological and biochemical study in guinea pigs fed normal or high cholesterol diet.

When guinea pigs were kept on a restricted vitamin C intake of only 0.5 mg daily, their serum ascorbic acid fell to 0.16 +/- 0.06 mg/d1 in 16 weeks as compared to 0.73 +/- 0.11 in control. This was associated with significant increase in liver cholesterol and triglycerides. When they were simultaneously challenged with a high cholesterol load, this fat accumulation was markedly exaggerated. The weight of the liver now increased by almost two-and-half times. Liver cholesterol rose to 12.90 +/- 2.63 mg/gm as compared to 3.23 +/- 0.56 mg/gm with low vitamin C alone. Histopathology showed marked distension and vacuolation of hepatocytes, focal necrosis and fibroplasia. Administration of excess vitamin C (100 mg daily) significantly countered these changes. The vitamin C-lipid relationship has important clinical bearings and liver could be an important site of vitamin C action.

Physiological role of dehydroascorbic acid.

Dehydroascorbic acid is present in insignificant amounts in plant and animal tissue but appears in considerable amounts under various physiological and pathological conditions. It is found increased: in blood of patients suffering from infectious diseases; in blood and tissues of thyrotoxic patients; in blood after injection of thyroxin, corticotropin and cortisone. In all the above conditions there is concomitant decrease in L-ascorbic acid and glutathione values of blood and tissues. Dehydroascorbic acid, however, disappears after continued administration of a high dose of ascorbic acid. The accumulation of dehydroascorbic acid seems to be an indication of ascorbic acid deficiency. The extreme sensitivity of the ascorbate system to physiological changes is suggestive of a major biochemical role for this redox system. Accumulated evidences indicate that dehydroascorbic acid possible control cell division.