Vitamin epithelia

Injury (either physical or chemical) to the comeal endothelial cells has a marked efiect on occular function as these cells are responsible for maintaining the thickness and clarity of the cornea, yet they cannot be replaced if damaged. Immunohistochemical studies have revealed that enzymatic antioxidant defences, SOD, CAT and GSHPx, are similarly distributed in the corneal epithelium and endothelium (Rao etal., 1985 Attala et d., 1987, 1988). Other antioxidants include ascorbate, carotenoids and vitamin E (Fleath, 1962). 

Bleaching is reversed in the dark and the red-purple color of rhodopsin returns. This is thought to occur by the reduction of all-Pms-retinal to vitamin Ai (retinal), which diffuses from the rod into the pigment epithelium, where it is converted enzymatically to the 1 l-c isomer of vitamin At. The enzymatic isomerization is followed by diffusion back into the rod, oxidation to 11 -rfr-retinal, and combination with opsin to form rhodopsin. This process is shown schematically in Figure 12.5.[Pg.289]

Vitamin A (carotene) is converted to several active forms in the body associated with two important functions, maintenance of healthy epithelium and vision. 

Deficienqr of vitamin A results in night blindness (rod cells are responsible for vision in low light), metaplasia of the corneal epithelium, dry eyes, bronchitis, pneumonia, and follicular hyperkeratosis. 

Vitamin A is essential for growth and development of cells and tissues. In its active form, retinoic acid (RA), it controls the regular differentiation as a ligand for retinoic acid receptors (RAR, RXR) and is involved in the integration (gap junction formation) of cell formations (Biesalski, 1996 Biesalski et al, 1999). Vitamin A plays a substantial role, especially in the respiratory epithelium and the lung. During moderate vitamin A deficiency, the incidence for diseases of the respiratory tract is considerably increased and repeated respiratory infections can be influenced therapeutically by a moderate vitamin A supplementation (Biesalski et ah, 2001 Greenberg et ah, 1997 John et ah, 1997). 

Vitamin A deficient endocervical, tracheal epithelium, continuous basal and squamous cells... 

FIGURE 5.2 Morphological changes of the bronchial epithelium of the respiratory tract during vitamin A deficiency. 

On the basis of a few reports, it is assumed that a "local vitamin A deficiency exists in meta- and dysplastic areas. Measurements of vitamin A concentrations in metaplastic areas of the respiratory epithelium and the cervix epithelium actually proved that vitamin A in comparison to the surrounding tissues was not found (Biesalski, 1996). Clearly one cannot say what is cause and effect. Studies carried out by Edes et al. (1991) confirm an induction of a vitamin A deficit. These studies showed that a depletion of vitamin A ester stores is caused by toxins, present in cigarette smoke (predominantly polyhalogenated compounds), in different tissues. 

By inhalative application of vitamin A, an accumulation of peripheral vifamin A stores is achieved. For the Irmg and the respiratory epithelium, concentrations in the range of 1-20 (ig/g were obtained (Biesalski, 1990). Looking at quantitative concentrations in the respiratory epithelium and in the mixed epithelium of the nasal mucosa yielded an accumulation of vifamin A — after topical administration in different animal species — in the epithelium of the nose increased by factor 10-100 (in human of factor 5-20) compared to the concentrations of the respiratory mucosa (Lewis, 1973). 

These results show that retinyl esters in respiratory epithelium and in alveolar cells form a pool of vitamin A, which can be used physiologically by the tissue. The formation of retinol and at least RA from retinyl esters is strictly controlled. So far an unphysiological formation of RA and a subsequent toxicity seems not possible. Retinyl esters, however, are biochemically inert with respect to gene expression or vitamin A activity as long as they are not hydrolyzed. Consequently, the inhalative application, especially in cases of insufficient lung development, could represent a true alternative. The oral contribution is hardly successful because of the poor RBP s)mthesis of the liver and the lack of availability of a parenteral solution is currently not available. 

Vitamin A deficiency is worldwide one of the most prevalent nutrition-dependent deficiency diseases. It leads to changes of the respiratory epithelium, which result in repeated infections of the respiratory tract, the main cause of death in vitamin A-deficient children. The difficulty in supplying the respiratory epithelium with vitamin A is that the affected children frequently suffer as well from infections of the gastrointestinal tract with subsequent reduction of the absorption of fat-soluble vitamins. Nutritargeting can in these cases avoid the problems of malabsorption and ensure the micronutrient supply. 

The animals treated with 200, 400, and 800 lU A showed a healing effect of vitamin A on the cornified vaginal epithelium as early as 2 days after starting the experiment. In the smear of all concentrations, almost exclusively leukocytes — indicating a successful healing and mucosal regeneration — with only sporadic epithelial cells and squamous cells... 

The obtained results confirm earlier findings where vitamin A-deficient rats were used to prove the uptake of retinyl esters into lung, liver, kidney, and plasma after inhalation thereof (Biesalski, 1996). However, long-term topical administration of high vitamin A concentrations is a well-established therapy in atrophic rhinitis, rhinitis sicca, and metaplastic changes in the nasal or ocular epithelium (Deshpande et ah, 1997 Simm, 1980). The application leads to the normalization of mucous membranes and reappearance of a normal function with no side effects. 

McDowell, E. M., Keenan, K. P., and Huang, M. (1984a). Effects of vitamin A-deprivation on hamster tracheal epithelium. A quantitative morphologic study. Virchows Arch. B Cell Pathol. Inch Mol. Pathol. 45,197-219. 

Stofft, E., Biesalski, H. K., Niederauer, U., Zschabitz, A., and Weiser, H. (1992b). Morphological changes in the tracheal epithelium of guinea pigs in conditions of "acute" vitamin A deficiency. Int. J. Vitam. Nutr. 62,143-147. 

Foster I don t know the mechanism whereby chromophore is retained. The bottom line is that we know chromophore is only depleted in flies and mice, and that most of the retinoid will be part of the visual system anyway. There must be some other way of retaining vitamin A. In fact in mammals, there are a whole range of potential vitamin A binding proteins, hke IRBP in the pigmented epithelium, that could serve to mop-up and act as a chromophore sink. 

In higher plants, carotenoids are produced in green leaves. In animals, conversion of carotenoids to vitamin A occurs in the intestinal wall. Storage is in the liver also kidney in rat and cat. Target tissues are retina, skin, bone, liver, adrenals, germinal epithelium. Commercial Vitamin A supplements are obtained chemically by extraction of fish liver or synthetically from citral or /3-ionone. 

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