Glutathione redox cycle in small intestinal mucosa and peripheral blood of pediatric celiac disease patients.

The celiac disease is an autoimmune gastrointestinal disorder caused by gluten from wheat, rye or barley. In genetically predisposed persons, gluten induces the immune-mediated inflammation of small intestinal mucosa. Histological lesions include intraepithelial lymphocytosis, crypt hypertrophy and villous atrophy, resulting in malabsorption of micro- and macronutrients. The only treatment for celiac patients is a permanent gluten-free diet (GFD). Reactive oxygen species (ROS) and oxidative stress are strongly associated with the celiac disease. Glutathione (GSH) is a main detoxifier of endogenous and exogenous ROS in the intestine. In order to explain the role of glutathione redox cycle in celiac patients, we examined the activities of GSH-related antioxidant (AO) enzymes glutathione peroxidase (GPx) and glutathione reductase (GR), as well as the concentration of GSH in small intestinal biopsies and peripheral blood of children affected by the celiac disease. The concentration of lipid hydroperoxides (LOOH) as markers of oxidative damage was measured in the same samples. The results clearly demonstrate a significant malfunction of GSH redox cycle with a concomitant decrease in the capacity to regenerate GSH and detoxify LOOH in celiac patients, even after several years of GFD. The oral administration of GSH and a diet rich in natural antioxidants, as well as appropriate dietary supplements, could be of great benefit to the patients.

Antioxidantes y envejecimiento cutáneo / Antioxodants and cutaneous aging

Las formulaciones disponibles actualmente para uso dermatológico, basadas en sustancias antioxidantes tales como vitaminas C y E, entre otras, abundan con promesas de revertir el envejecimiento cutáneo. En el presente trabajo se realiza una revisión de los sistemas antioxidantes cutáneos, de la relación entre envejecimiento y daño oxidativo, así como de la evidencia disponible en cuanto al tratamiento con antioxidantes. La intención de este artículo es que el dermatólogo comprenda las bases fisiológicas de acción de los antioxidantes, para poder juzgar su utilidad con una mirada crítica

Antioxidantes y envejecimiento cutáneo / Antioxodants and cutaneous aging

Las formulaciones disponibles actualmente para uso dermatológico, basadas en sustancias antioxidantes tales como vitaminas C y E, entre otras, abundan con promesas de revertir el envejecimiento cutáneo. En el presente trabajo se realiza una revisión de los sistemas antioxidantes cutáneos, de la relación entre envejecimiento y daño oxidativo, así como de la evidencia disponible en cuanto al tratamiento con antioxidantes. La intención de este artículo es que el dermatólogo comprenda las bases fisiológicas de acción de los antioxidantes, para poder juzgar su utilidad con una mirada crítica (AU)

Role of antioxidant enzyme expression in the selective cytotoxic response of glioma cells to gamma-linolenic acid supplementation.

We hypothesized that the cytotoxic effect of GLA observed in glioma but not normal glial cells reflects differences in GLA metabolism and/or antioxidant enzyme levels between these cells. The PUFA content of unsupplemented glioma cells was approximately 50% of that seen in unsupplemented astrocytes. Supplementation with 20 microM GLA for 24 h led to a 230 and 22% increase in glioma and astrocyte PUFA content, respectively, such that both supplemented cell types contained similar levels of PUFA. No major differences were seen in terms of GLA metabolites retained in the cells or secreted into the media following incubation with [(3)H]-GLA. No significant differences were observed in activity of MnSOD or CuZn-SOD between the cells. However, CAT and GPx activity in the glioma cells was significantly higher and lower, respectively, than observed in normal astrocytes. GLA supplementation resulted in a significant increase in CAT activity in normal astrocytes; glioma CAT activity was unchanged. No significant change was seen in the other antioxidant enzymes following GLA supplementation. These results suggest that the cytotoxic effect of GLA on glioma cells reflects both increased PUFA content and an inability to upregulate CAT.

Omega 3-lipid peroxides injure CaCo-2 cells: relationship to the development of reduced glutathione antioxidant systems.

BACKGROUND/AIMS: Dietary polyunsaturated fats are significant sources of luminal lipid hydroperoxides whose accumulation can be injurious to the intestinal epithelium. The current study examines the cytotoxicity of peroxidized fish oil to CaCo-2 cells. METHODS: Chromate release from cells was used as an index of CaCo-2 injury, and day 1 and day 7 postconfluent monolayers were used to represent the immature and mature states, respectively. RESULTS: Air oxidation of fish oil yielded equimolar quantities of hydroperoxyeicosapentaenoic (20:5) and docosahexaenoic (22:6) acids. Their cytotoxicity were time- and concentration-dependent and were related to the developmental stages. A 100-mumol/L dose of hydroperoxides caused a 40% and a 15% 51Cr release from day 1 and day 7 cells, respectively. Cellular glutathione (GSH), GSH redox enzyme, and gamma-glutamyl cysteine synthetase activities were significantly lower in day 1 than in day 7 cells, indicating that hydroperoxide metabolism in immature cells is rate limited by reductant supply. GSH supplementation increased cell GSH in day 7 cells (twofold) but not in day 1 cells, suggesting a limited ability of immature cells to use exogenous GSH. CONCLUSIONS: These results show that nondifferentiated cells are more sensitive to oxidant-induced injury than mature cells. This enhanced susceptibility is associated with a lower GSH-dependent detoxication capacity of the immature cells.