Vitamin C and the immune response.

The inclusion of vitamin C in the drinking water of BALB/c mice was without effect on the humoral antibody response to sheep red blood cells and bacterial lipopolysaccharide. However, there was a significantly increased cell-mediated immune response as determined by increased T-lymphocyte responses to concanavalin A. This might suggest a mechanism, along with interferon enhancement, for the possible protection by vitamin C against some viral infections.     

The endothelial cell protein C receptor: cell surface conductor of cytoprotective coagulation factor signaling

Increasing evidence links blood coagulation proteins with the regulation of acute and chronic inflammatory disease. Of particular interest are vitamin K-dependent proteases, which are generated as a hemostatic response to vascular injury, but can also initiate signal transduction via interactions with vascular receptors. The endothelial cell protein C receptor (EPCR) is a multi-ligand vitamin K-dependent protein receptor for zymogen and activated forms of plasma protein C and factor VII. Although the physiological role of the EPCR-FVII(a) interaction is not well-understood, protein C binding to EPCR facilitates rapid generation of APC in response to excessive thrombin generation, and is a central requirement for the multiple signal-transduction cascades initiated by APC on both vascular endothelial and innate immune cells. Exciting recent studies have highlighted the emerging role of EPCR in modulating the cytoprotective properties of APC in a number of diverse inflammatory disorders. In this review, we describe the structure–function relationships, signal transduction pathways, and cellular interactions that enable EPCR to modulate the anticoagulant and anti-inflammatory properties of its vitamin K-dependent protein ligands, and examine the relevance of EPCR to both thrombotic and inflammation-associated disease.     

Chemical evidence for interactions between vitamins E and C

Experimental proof is provided for interactions between radicals of vitamin E/vitamin C as generated by air-oxidized lipids (liquid fraction of subcutaneous chicken fat). Using ESR spectroscopy, hydrogen atom exchange is shown to take place between vitamin C and the radical of vitamin E. Sequential consumption of these two vitamins in oxidized lipid, first vitamin C then vitamin E, is demonstrated by means of differential pulse polarography. These results elucidate the in vitro radical scavenging functions attributed to vitamin E and vitamin C as well as their synergism in lipid antioxidation.     

Chemical evidence for interactions between vitamins E and C

Summary Experimental proof is provided for interactions between radicals of vitamin E/vitamin C as generated by air-oxidized lipids (liquid fraction of subcutaneous chicken fat). Using ESR spectroscopy, hydrogen atom exchange is shown to take place between vitamin C and the radical of vitamin E. Sequential consumption of these two vitamins in oxidized lipid, first vitamin C then vitamin E, is demonstrated by means of differential pulse polarography. These results elucidate the in vitro radical scavenging functions attributed to vitamin E and vitamin C as well as their synergism in lipid antioxidation.The authors very much thank Dr A. Dieffenbacher and P. Ducret for the preparation of the chicken fat fraction.     

Photoperiodic induction of diapause in an insect is vitamin A dependent

Summary A photoperiodic response was found to be absent in larvae of the parasitoid waspApanteles glomeratus when its host (caterpillars ofPieris brassicae) was reared on a low-carotenoid artificial diet. Addition of vitamin A to the host's diet restored the response to short-day photoperiods in the wasp larvae, thus showing that vitamin A is essential for photoperiodic induction of diapause. Possibly vitamin A or a derivative of vitamin A functions as the photoreceptor pigment for the photoperiodic reaction in this species of insect.     

Role of 1,25-dihydroxyvitamin D3 in the generation of the acute-phase response in rats with talc-induced granulomatosis

Subcutaneous injection of nonspecific irritants such as magnesium silicate (talc) provokes granulomatous inflammation in the rat. Part of the acute phase response (APR) in these animals is the loss of trabecular bone at sites distant from the site of inflammation. To assess the possible involvement of vitamin D in the bone loss, we studied the development of the acute phase response in vitamin D-deprived rats. The serum APR provoked by subcutaneous inflammation in rachitic rats consisted of hypozincemia, hypercupremia, increased, alkaline phosphatase activity and adrenocorticotropic hormone (ACTH) concentration, and was similar to that in control animals except for the absence of hypoferremia. Control rats with talc-induced subcutaneous inflammation also had splenomegaly and decreased total and mononuclear peripheral blood cell counts, while subcutaneous inflammation did not induce spleen changes in rachitic rats. Subcutaneous inflammation induced the loss of trabecular bone and decreased the osteoblastic cell count in tibial metaphyses in control animals. Rachitic rats had abundant osteoid on trabecular surfaces, and the number of osteoblasts and osteoclasts was comparable to that of the controls. Subcutaneous inflammation did not affect any of the bone parameters in rachitic rats. These results indicate that vitamin D plays an important role in the generation of the acute phase response during inflammation, particularly in the induction of spleen and bone cell changes. The discrepancy of the blood on one hand and bone and spleen indices of the APR on the other, indicate that there may be divergent pathways in the generation of the inflammatory response, some of which may be dependent on vitamin D.     

Effect of aspirin and vitamins C and E on synovial rheumatoid arthritic and other cells.

Normal and rheumatoid arthritic human synovial cells, normal rat muscle and bone cells, were cultured with combinations of aspirin (acetylsalicytic acid), vitamins C and E. Aspirin reduced percent growth of all cells by about 1/5 relative to controls. High vitamin C eradicated arthritic cells. In combinations, vitamin C was most important in eradicating arthritic cells. A low-vitamin C combination was most effective in reducing arthritic cell populations, while having little effect on normal cells. Vitamin E retarded but did not prevent the action of vitamin C.     

Effect of aspirin and vitamins C and E on synovial rheumatoid arthritic and other cells

Summary Normal and rheumatoid arthritic human synovial cells, normal rat muscle and bone cells, were cultured with combinations of aspirin (acetylsalicytic acid), vitamins C and E. Aspirin reduced percent growth of all cells by about 1/5 relative to controls. High vitamin C eradicated arthritic cells. In combinations, vitamin C was most important in eradicating arthritic cells. A low-aspirin, low-vitamin C combination was most effective in reducing arthritic cell populations, while having little effect on normal cells. Vitamin E retarded but did not prevent the action of vitamin C.Acknowledgment. This work was supported by NRC grant No. A 6445 to Dr Bhakthan, Department of Kinesiology, Simon Fraser University.     

Dietary vitamin E does not protect from endotoxin-induced hepatic microvascular dysfunction

Starting from the concept that lipopolysaccharide (LPS)-associated hepatotoxicity involves the action of reactive oxygen species, the present study was conducted to test whether vitamin E, a lipophilic antioxidant, prevents LPS-induced hepatic microvascular dysfunction and liver injury. Fifty-two rats were divided into three groups and fed diets containing 0 (n=16), 75 (n=18) or 8000 mg (n=18) α-tocopherol acetate/kg food for four weeks. At 1 h and 6 h after intravenous LPS-exposure (10 mg/kg E. coli LPS) hepatic microvascular response and liver injury were assessed by the analysis of Kupffer cell phagocytic activity, leukocyte-endothelial cell interaction and nutritive sinusoidal perfusion (intravital fluorescence epi- illumination technique) as well as bile flow, serum liver enzyme activities and tissue histomorphology. In animals fed with 75 mg vitamin E/kg (standard diet), LPS caused hepatic Kupffer cell activation (increased phagocytic activity) and hepatic microvascular leukocyte activation, with stasis in sinusoids and adherence in postsinusoidal venules (1 h) followed by leukocytic infiltration into tissue (6 h) and progredient sinusoidal perfusion failure (6 h). Hepatic microvascular injury was accompanied by reduced bile flow and enhanced liver enzyme release. Vitamin E-enriched diet (8000 mg/kg) and even vitamin E-deficient diet did not significantly affect LPS-induced hepatic microvascular cell activation and perfusion failure. Thus, we conclude, that vitamin E is not effective to protect from endotoxin-induced hepatic microvascular dysfunction. Received 7 November 1996; received after revision 30 December 1996; accepted 20 January 1997     

Action des différentes formes actives de la vitamine A sur le mécanisme immunitaire chez le rat

Summary In this work, we have studied the role of different active forms of vitamin A considered as adjuvant of the immune mechanism in the rat. We also pointed out the adjuvant effect of retinol and retinal in comparison with the other active components of that vitamin with the bovine -globulin which is not an immunogenic antigen in itself in the control rat. Despite the fact that vitamin A has no antigenecity, it still possess an extrinsic adjuvanticity in presence of bovine -globulin. The degree of the immune response is increased.

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Action des différentes formes actives de la vitamine A sur le mécanisme immunitaire chez le rat

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Supporté par le C.N.R.S., Liban.     

Occurrence of retinal and 3-hydroxyretinal in a possible photoreceptor of the silkworm brain involved in photoperiodism

Summary Deficiency of dietary carotenoid and vitamin A caused an absence of photoperiodic response of diapause induction in the silkworm,Bombyx mori, and an addition of vitamin A to the diet restored the response. By high pressure liquid chromatography (HPLC) a possible photoperiodic receptor of the silkworm brain was found to contain both retinal and 3-hydroxyretinal which are chromophores of insect visual pigments. These pieces of evidence suggest that a retinoid protein might function in the photoperiodic response of the silkworm.     

The identification of dehydroretinol (vitamin A2) in human skin

Summary Vitamin A₂ has for the first time been identified in a human tissue and, in contrast to vitamin A₁, its concentration in the epidermis is markedly increased in a hyperkeratotic condition (Psoriasis vulgaris).Acknowledgments. The valuable discussions with Prof. I. Björk, Drs A. de Belder, C. Lindberg and J.B. Lee are gratefully acknowledged. Purified retinoids were generously supplied by F. Hoffmann-LaRoche Co. AG, Basle. This project was supported by grants from the Swedish Medical Research Council (B78-03x-05174), the Welander Foundation and the Tore Nilsson Fund.     

The effects of vitamin A nutritional status on glutathione levels and microsomal lipid peroxidation in rat lung

Summary In vitamin A-deficient rats, the glutathione level in lung was diminished and microsomal lipid peroxidation much increased. In vitamin A-loaded animals, however, both were depressed below control. Thus vitamin A protection against lipid peroxidation is independent of glutathione.Acknowledgments. We thank Dr L. Y. Y. Fong and Mr David Y. H. Woo for preparing the animals used in this research, for retinol determinations and for valuable discussions, and also the China Medical Board of New York and the University of Hong Kong for the award of a Fellowship to V.P.     

A synergistic interation between the teratogenic effect of trypan blue and dietary deficiency in the rat

Summary There was a increased incidence, compared to controls, of exencephaly and micropthalmia in the offspring of rats fed a vitamin D deficient diet and injected with trypan blue on day 9 of gestation. Oral vitamin D did not reverse the effect.Acknowledgments. The author wishes to thank Dr G. Lumb and Dr. B. Mawer for advice on diets, and Mrs de Silva for making the assays.     

A synergistic interaction between the teratogenic effect of trypan blue and dietary deficiency in the rat.

There was an increased incidence, compared to controls, of exencephaly and microphthalmia in the offspring of rats fed a vitamin D deficient diet and injected with trypan blue on day 9 of gestation. Oral vitamin D did not reverse the effect.     

Effect of retinyl acetate feeding on the activity of testicular enzymes in young rats

Summary Feeding of excess vitamin A significantly increased the activity of -galactosidase and -glucuronidase without effecting the activity of acid and alkaline phosphatase in rat testicular homogenates. It is suggested that imbalance of vitamin A affects the normal process of spermatogenesis by altering the activity of lysosomal enzymes.Acknowledgments. The author is grateful to Dr C.M. Singh, I.V.R.I., Izatnagar and Dr L.N. Singh, for providing facilities and encouragement and to Prof. O. Isler, Hoffmann-La Roche, Basel, Switzerland, for the generous supply of retinyl acetate used in this work.     

Effect of vitamin A on tumor development in burned, unburned, and glucocorticoid-treated mice inoculated with an oncogenic virus.

High doses of vitamin A decreased the severity of tumor development in mice inoculated with a murine sarcoma virus; the same doses of vitamin A had no effect on the increased tumorigenesis seen in animals severely stressed with thermal injury or the increased tumorigenesis induced by exogenous glucocorticoid administration.     

The effects of vitamin A nutritional status on glutathione levels and microsomal lipid peroxidation in rat lung

In vitamin A-deficient rats, the glutathione level in lung was diminished and microsomal lipid peroxidation much increased. In vitamin A-loaded animals, however, both were depressed below control. Thus vitamin A protection against lipid peroxidation is independent of glutathione.     

The effects of vitamin A nutritional status on glutathione, glutathione transferase and glutathione peroxidase activities in rat intestine

In rat intestine, the glutathione level was increased, glutathione peroxidase activity decreased and glutathione-S-transferase unchanged by vitamin A deficiency.