In vitro immune response of human peripheral blood cells to vitamins C and E.

Since oxygen free radicals exert a noxious effect on cell functions, the purpose of the study was to examine the influence of the antioxidant vitamins C and E on the phagocytic capacity, apoptotic death, production of TNFalpha and IL-10 by human peripheral blood cells. In addition, an attempt to find a correlation between the effect of these vitamins on apoptosis and DNA synthesis was carried out. Peripheral white blood cells obtained from 27 healthy volunteers were incubated for 24 hr without and with vitamins C and E at doses extrapolated from clinical practice. Incubation of cells with vit. C caused a significant increase in the number of latex particles internalized by each individual polymorphonuclear cell, but not by monocytes. Both vitamins did not change the number of cells capable for phagocytosis. By the method of propidium iodide staining for detection of apoptosis, incubation of the cells with 0.2 mg/mL vit. C for 24 hrs caused a 39% increase in the percentage of apoptotic cells, as compared to those kept at the same incubation conditions without vitamin. 0.125 mg/mL of vit. E did not affect the percentage of apoptotic cells. On the other hand, applying the caspase-3 method for apoptosis detection, vitamins C and E did not affect the caspase-3 activity. Both vitamins caused an inhibition of 3H-TdR incorporation, which was dose-dependent for vit. C. Concentrations of the vitamins lower than those mentioned above did not alter DNA synthesis. While TNFalpha production was not affected by both vitamins, the spontaneous secretion of IL-10 was dose-dependently reduced by vit. C but remained unaltered following incubation with vit. E. The results, although observed in vitro, might be of importance when those vitamins are administered to healthy subjects.

Ultrastructure of mouse striated muscle fibers following pravastatin administration.

To examine the effect of pravastatin administration on striated muscle ultrastructure, 10 BalbC mice were given pravastatin 40 mg/kg/day for 3 weeks. At the end of the study, blood was withdrawn for evaluation of the serum creatine phospho-kinase (CPK) level and the muscles of the hind legs, as well as the heart and liver of the animals were examined with a light and transmission electron microscope. After treatment with pravastatin the results showed a 101% increase in serum CPK level in comparison to untreated controls. Hematoxillin-eosin stained tissues of pravastatin treated mice did not show any abnormal findings. While the ultrastructure of the heart and liver of the treated animals appeared normal, the muscle fibers showed a marked alterations of the mitochondria, which were increased in size compared to those of the controls. The cristae were heavily damaged and even completely destructed, giving the mitochondria appearance of empty vacuoles. The findings are in favor of a specificity of pravastatin for striated muscles.