Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042875 (vitamin E deficiency)
 916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies in young normal rats have shown that intracerebral administration of the proteinase inhibitor, leupeptin, caused a rapid accumulation of lipofuscin-like pigment in lysosomes of brain cells (Ivy et al., 1984a). On the other hand, we have recently found that the administration of lovastatin, an inhibitor of HMG-CoA reductase, reduced the ceroid-like pigment and dolichol contents in the crushed epididymal fat pad of rats (Porta et al., 1988). In order to study now the possible modulating effects of these enzyme inhibitors on ceroidogenesis associated with vitamin E deficiency, two main groups of weanling Wistar female rats were respectively fed ad libitum a vitamin E-deficient basal diet, or the same diet supplemented with 16 mg% of dl-alpha-tocopherol acetate. The vitamin E-deficient and -supplemented rats were further subdivided and received for 8 weeks their diets alone or with 2, 1, or 0.5 g of lovastatin/kg of diet. Other subgroups were treated with constant peritoneal infusion of 0.5 mg/day of leupeptin by means of osmotic minipumps (Alzet 2002) consecutively implanted at days 15, 30, and 45. Lovastatin treatment to vitamin E-deficient rats was associated with dose-dependent toxicity, resulting in 100%, 75%, and 50% mortality at concentrations of 2, 1, and 0.5 g/kg diet, respectively. This mortality was mainly due to extensive hepatic necrosis. Food intake and growth rates were reduced, while the relative weights of liver, kidneys, spleen, heart and brain, as well as the serum levels of GPT and GOT were significantly increased over the values of the untreated vitamin E-deficient control rats. The volumetric densities of ceroid pigment and the dolichol contents in liver and kidneys were not significantly modified. Lovastatin toxicity was partially prevented by vitamin E supplementation. However, in these supplemented rats, lovastatin treatment did not modify the volumetric densities of hepatic and renal ceroid, although the contents of hepatic and renal dolichol were significantly increased. No correlations could be found between levels of hepatic or renal ceroid and total dolichol content in vitamin E-deficient and supplemented rats. Leupeptin treatment to vitamin E-deficient rats only slightly reduced food intake and growth rates, and did not significantly modify the relative organ weights or the serum levels of cholesterol, GOT and GPT. Although in both vitamin E-deficient and -supplemented rats the leupeptin treatment consistently showed a tendency to increase the volumetric densities of hepatic and renal ceroid pigment, the differences with the control untreated rats were not statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of lovastatin and leupeptin on ceroidogenesis of vitamin E-deficient and -supplemented young rats. 248 49

The effects of vitamin E deficiency on the rat testis and epididymis were examined in a light- and electron-microscopic analysis. Various groups of animals were made vitamin E-deficient, beginning at postnatal day 10, via their lactating mothers, until day 21, when they were separated from their mothers. The groups were maintained thereafter on either a vitamin E-deficient or a normal diet (controls). The vitamin E-deficient animals of group A, sacrificed at day 42, revealed testes that were normal in appearance, with a full complement of germ cells when compared to their controls (group B). Group C, however, sacrificed at day 48, revealed major abnormalities in the testes, unlike both their controls (group D) and normal, untreated animals (group E). Spermatogenesis was incomplete; the most advanced cell type was predominantly step-7 spermatids. However, many of these cells, as well as earlier spermatids, appeared to undergo degeneration, evidenced by large pale areas in their nuclei, disrupted acrosomes, and a cytoplasm with uncharacteristic organelles. Multinucleated cells, characterized by their chromatoid bodies as spermatids, were often seen in the seminiferous tubule lumen. Sertoli cells were normal in appearance, except for numerous, large lipid droplets in their basal region, at stages I-VIII; in appropriate controls (group D), such droplets were absent at these stages. These lipid inclusions presumably represented the final breakdown products of the late spermatids, which were phagocytosed by Sertoli cells between days 42 and 48. However, numerous germ cells, often recognized as round spermatids, and multinucleated cells were noted in the epididymal lumen, which indicates that such cells were spared from Sertoli cell phagocytosis. These data suggest that vitamin E plays a key role in the maintenance and survival of spermatids. In the epididymis, vitamin E deficiency resulted in principal, narrow, and apical cells that showed a poorly developed secretory and endocytic apparatus at days 42 (group A) and 48 (group C), unlike those of normal, untreated animals (group E). On the other hand, clear cells of groups A and C showed a highly developed endocytic apparatus in the cauda region only, whereas in the caput and corpus regions, endocytic apparatuses were small and undifferentiated, unlike those of group E. Thus, in the epididymis, vitamin E plays a role in the structural differentiation of principal cells along the entire epididymis, whereas, in the case of clear cells, its role is region-specific. Readministration of vitamin E to the diet restored a normal appearance to both the testis and the epididymis, which indicates that the effects on these tissues are reversible. Taken together, these data indicate that vitamin E plays important roles in maintaining the viability of the spermatid population and in allowing epithelial epididymal cells to acquire their fully differentiated structural appearance.
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PMID:Vitamin E deficiency causes incomplete spermatogenesis and affects the structural differentiation of epithelial cells of the epididymis in the rat. 963 44