Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 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

An initial dose-range pilot study where animals were gavaged with between 100 and 1600 mg tri-o-cresyl phosphate (TOCP)/kg/day for 14 days resulted in decreased epididymal sperm density and disruption of the seminiferous epithelium in 100% of treated animals. A subchronic 63-day study (reflecting the 49-day length of the rat seminiferous epithelium cycle plus the 14-day transit time of spermatids through the epididymis was initiated. Dose-dependent (10 to 100 mg TOCP/kg/day) decreases in cauda epididymal sperm motility and density, testicular enzyme activities, and alterations in sperm morphology were observed. Concurrent pair-fed controls (matched to the highest dose group, 100 mg TOCP/kg/day) indicated that weight loss resulting from TOCP administration had minimal contributory effects to the testicular toxicity seen. Plasma alpha-tocopherol acetate (vitamin E) and testosterone concentrations were unaffected. Tri-p-cresyl phosphate (TPCP), the nonneurotoxic structural analog of TOCP, produced no toxic effects, demonstrating the necessity of the ortho-cresol moiety for induction of damage. A minimum effective (threshold) dose for observable testicular toxicity was determined to be 10-25 mg TOCP/kg in this study. These data suggest that TOCP interferes with spermatogenic processes and sperm motility directly and not via an androgenic mechanism or decreased vitamin E availability.
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PMID:Reproductive tract lesions resulting from subchronic administration (63 days) of tri-o-cresyl phosphate in male rats. 359 Jan 88

The effects of the dietary ratio of polyunsaturated/saturated fatty acids (P/S) and dietary vitamin E on lipid peroxidation (LP) were examined to determine whether the vitamin E requirement is elevated by increased P/S in ratios comparable to those found in human diets. Twelve groups of male weanling rats (six/group) were fed purified diets containing 20% fat with P/S ratios of 0.38, 0.82 or 2.30. At each P/S level, groups of rats received either 0, 10, 40 or 100 IU vitamin E/kg diet supplied as all-rac-alpha-tocopherol. After the diets were fed for 16 wk, in vivo LP was assessed by measuring pentane in expired breath. Pentane levels were significantly elevated in rats fed 0 IU vitamin E at all P/S levels. Both 40 and 100 IU vitamin E decreased pentane production to minimal levels for all P/S groups. Liver malondialdehyde levels and in vitro spontaneous red blood cell hemolysis results also indicated a significant effect of vitamin E in reducing in vitro LP, but no overall effect of P/S. Testicular and epididymal histology showed no effect of dietary P/S on the vitamin E requirement. These data demonstrated 40 IU vitamin E to be adequate for maximal inhibition of LP at the P/S levels tested and indicated that these levels of dietary P/S had no significant impact on the vitamin E requirement for the growing rat.
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PMID:Effect of dietary polyunsaturated/saturated fatty acid ratio and dietary vitamin E on lipid peroxidation in the rat. 405 39

To investigate the effect of dietary oxidized frying oil (OFO) on tissue retention of alpha-tocopherol (alpha-T). Long-Evans male weanling rats were divided to four groups based on a 2 x 2 factorial design. Two groups were fed 15% OFO diets, and the remaining two groups were fed control diets in which OFO was replaced by vitamin-E-stripped fresh soybean oil. Vitamin E as all-rac-alpha-tocopheryl acetate was added at the concentration of either 50 (normal E) or 500 (high E) mg/kg diet. The OFO sample was prepared by deepfrying sticks in fresh soybean oil at 205 +/- 5 degrees C for four 6-h periods. After 6 wks of feeding, alpha-T concentrations in most tissues were significantly lower in rats fed OFO diets (P < 0.05) than in the control groups. For rats fed the OFO diet with the normal vitamin E concentration, the alpha-T concentration is epididymal fat pad, plasma, liver, kidney, muscle, brain and lung were 29-64% those of the corresponding control group (P < 0.05). The interaction between the two dietary factors on tissue alpha-T was significant in liver, spleen, and adrenal gland. In these three tissues, the differences between the normal and high dietary vitamin E groups were less in rats fed the OFO diets than in rats fed the control diets. The tissue alpha-T concentrations of the high vitamin E OFO group were comparable with or higher (P < 0.05) than those of the normal vitamin E control group, indicating that the negative effect of OFO on tissue alpha-T concentration can be alleviated by dietary supplementation of vitamin E. Compared with the controls, rats OFO diets had significantly higher tissue thiobarbituric acid reactive substances (P < 0.05). Because the amount of alpha-T directly added into the test oil samples was not significantly decreased through an incubation (at 37 degrees C) period of up to 10 d, the inefficient absorption and/or enhanced catabolism or turnover of vitamin E may be involved in the inferior tissue alpha-T retention of OFO fed rats.
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PMID:Tissue alpha-tocopherol retention in male rats is compromised by feeding diets containing oxidized frying oil. 750 Jan 86

Little is known at present about the saccharide components of lipofuscin (age pigment) and ceroid pigments in situ. The purpose of this study was, therefore, to study in detail the lectin reactivities of lipofuscin in neurons and cardiac myocytes of old humans and rats. In addition, those of diverse ceroid pigments found in human aortic atheromas, in the livers of choline-deficient rats, in the uteri of vitamin E-deficient rats and in the crushed epididymal fat pad of rats, are included. Cryostat and deparaffinized sections from all these tissues were either extracted with a solvent mixture of chloroform-methanol-water (10:10:3, v/v) and incubated with 7 different biotinylated lectins or left untreated. Delipidation was done in order to study whether it was possible to discriminate between the saccharide moieties of glycolipids and glycoproteins of lipofuscin and ceroid pigments in situ. Other similarly treated sections were used to study the autofluorescence, sudanophilia, acid-fastness and reactivity to PAS. The frequency and intensity of lectin binding and standard histochemical properties of all the pigments were evaluated semi-quantitatively and blind. The results indicated that mannose was in general the most consistently detected sugar residue in lipofuscin granules of humans and rats, and that this pigment may also contain acetylglucosamine, acetylgalactosamine, sialic acid, galactose and fucose. However, notable differences were found not only in the lipofuscin saccharide components of different cell types of humans and rats, but also in those in the same type of cells in both species. Although mannose was not detected in the hepatic ceroid of choline-deficient rats, this saccharide moiety was almost always present in the other ceroid pigments. Each of the ceroids also contained other types of saccharides although the frequency of the latter varied between different ceroid pigments. While lipofuscin and each of the ceroid pigments showed somewhat different lectin binding patterns, the variability in the frequency of reactivity to lectins suggests that these patterns may not be permanent but transient. In this sense, it appears that lectin histochemistry may not allow these pigments to be differentiated. Furthermore, the extractive procedures used in this study did not enable us to determine whether the saccharides detected in the pigments in situ corresponded to glycolipids or glycoproteins.
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PMID:Lectin histochemistry of lipofuscin and certain ceroid pigments. 758 50

Rats fed a diet containing 15% oxidized frying soybean oil (OFO) have been shown to have significantly lower tissue alpha-tocopherol (alpha-T) concentration than rats fed a 15% fresh soybean oil diet. To examine the turnover of alpha-tocopherol, a depletion-repletion experiment and a radioisotope tracer study were conducted. Two groups of male weanling Long-Evans rats were fed vitamin E-deficient diets containing either 15% OFO or 15% vitamin E-stripped fresh soybean oil (control). After 9 wk of depletion, rats fed the OFO diet had significantly higher plasma pyruvate kinase (PK) activity and lower concentrations of alpha-T in RBC, adrenal gland, heart, kidney, liver, spleen, testis and muscle compared with controls (P < 0.05), indicating that the vitamin E-deficient status was aggravated by feeding the OFO diet. After 12 wk, the depleted rats were intraperitoneally injected with a dose of all-rac-alpha-T (2.5 mg/rat, dissolved in Vitamin E-stripped corn oil) every other day. Three doses were administered to each rat during the 1-wk repletion period. Plasma PK activity decreased in both groups (P < 0.05) after repletion but that of the OFO rats was still significantly higher than that of the control group. The repleted OFO gorup also had significantly lower alpha-T concentration in adrenal gland, epididymal fat, liver and spleen than the repleted control group. Two rats from each group that had been vitamin E-depleted for 16 wk were injected intraperitoneally with a single dose of 5-methyl-14C-RRR-alpha-T (740 kBq/kg body weight). During the week after dosing, the radioactivity excreted in urine and feces of the OFO group was 1.3- and 1.7-fold, respectively, that of the control group. Tissue retention of radioactivity was also lower in the OFO rats than in the control rats. The results suggest that more of the alpha-T in the body was catabolized or turned over in rats fed the OFO-containing diet.
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PMID:Dietary oxidized frying oil enhances tissue alpha-tocopherol depletion and radioisotope tracer excretion in vitamin E-deficient rats. 881 11

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

Mammalian caput and cauda epididymidal spermatozoa exhibit diverse stages of maturation, and their plasma membrane shows diverse composition and stability levels, thus enabling these spermatozoa to undergo the acrosomal reaction after transit through the epididymis. As a result, the study of antiperoxidative mechanisms is quite relevant, since epididymal spermatozoa must be properly protected against agents such as reactive oxygen species, which can impair the complex maturation process. We considered activities of certain enzymes (glutathione peroxidase [GPx], phospholipid hydroperoxide glutathione peroxidase [PHGPx], glutathione reductase [GR], superoxide dismutase [SOD], and catalase [CAT]) and the vitamin E content in isolated rat caput and cauda epididymidal spermatozoa. The results indicate that caput epididymidal sperm have significantly greater PHGPx (3.5x), GPx (2.4x), and SOD (1.7x) activities, as well as a greater amount of vitamin E (3.8x). There were no detectable differences in the GR and CAT activities of caput and cauda epididymidal spermatozoa. The substantial drop in PHGPx activity during epididymal transit is discussed in relation to an additional function of this enzyme: the use of caput sperm protamines as a sulfhydryl substrate. In vitro peroxidation of the two sperm populations by the free radical generator (azo-initiator) 2,2'-azobis(2-amidinopropane) dihydrochloride revealed that only about 13% of the vitamin E content of the caput epididymidal spermatozoa was consumed, which contrasts with the greater consumption (about 70%) of the vitamin in cauda epididymidal spermatozoa. Selective inhibition of PHGPx, SOD, or CAT did not change this picture. The higher susceptibility of cauda epididymidal spermatozoa to radicals is discussed in relation to the diverse enzymatic activities, vitamin E content, and peroxidative response. These factors are correlated with the different stages of sperm cell maturation, which are characterized-from caput to cauda epididymidis-by progressive destabilization of the plasma and acrosomal membranes.
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PMID:Antioxidant systems in rat epididymal spermatozoa. 974 22

This study was undertaken to investigate whether treatment with vitamin E (VE) and/or vitamin C (VC) protects rat sperm by inhibiting reactive oxygen species generation induced by lead (Pb) exposure. Male Sprague-Dawley rats were assigned to the following five groups: vitamin-unsupplemented; 150 mg VE/kg chow supplemented; 300 mg VE/kg chow supplemented; 500 mg VC/l drinking water supplemented and 150 mg VE/kg chow + 500 mg VC/l drinking water supplemented group. Rats in each group were divided into Pb-unexposed and Pb-exposed subgroups, received weekly intraperitoneal injection of 10 mg sodium acetate or 10 mg Pb acetate/kg for 6 weeks, respectively. The blood and sperm Pb levels were analyzed by graphite furnace atomic absorption spectrophotometer. Chemiluminescence was measured to evaluate the generation of sperm reactive oxygen species (ROS). Motility and sperm-oocyte penetration rate (SOPR) were measured. In Pb-unexposed rats, epididymal sperm counts, motility, ROS, and SOPR were not different in the five supplemented groups. Lead exposure might decrease the defense capacity of sperm to the oxidative stress and therefore elevate the ROS generation, reduce sperm motility, and reduce SOPR. Supplementation with VE and/or VC reduced ROS generation, prevented loss of motility and capacity of oocyte penetration in Pb-exposed rats. This study suggests that supplementation with VE and/or VC inhibits Pb-related ROS generation, protects spermatozoa from loss of motility and oocyte penetration capability.
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PMID:Effects of vitamin E and/or C on reactive oxygen species-related lead toxicity in the rat sperm. 975 40

In a randomized, placebo-controlled, double-blind study we investigated whether high-dose oral treatment with vitamins C and E for 56 days was able to improve semen parameters of infertile men. Ejaculate parameters included semen volume, sperm concentration and motility, and sperm count and viability. Thirty-one patients without genital infection but with asthenozoospermia (< 50% motile spermatozoa) and normal or only moderately reduced sperm concentration (> 7 x 10(6) spermatozoa/ml) (according to WHO criteria) were examined. To investigate the influence of the epididymal storage period on semen parameters, the patients were asked to deliver two semen samples with abstinence times of 2 and 7 days both before and at the end of vitamin treatment. After randomization, the patients received either 1000 mg vitamin C and 800 mg vitamin E (n = 15) or identical placebo capsules (n = 16). No changes in semen parameters were observed during treatment, and no pregnancies were initiated during the treatment period. Combined high-dose antioxidative treatment with vitamins C and E did not improve conventional semen parameters or the 24-h sperm survival rate. Prolonged abstinence time increased ejaculate volume (P < 0.05), sperm count (P < 0.05), sperm concentration (P < 0.05) and the total number of motile spermatozoa (P < 0.05).
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PMID:Antioxidant treatment of patients with asthenozoospermia or moderate oligoasthenozoospermia with high-dose vitamin C and vitamin E: a randomized, placebo-controlled, double-blind study. 1060 Nov 11


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