Acid Succinate Research Articles

Ototoxicity caused by cisplatin is ameliorated by melatonin and other antioxidants.

The mechanism of the ototoxicity caused by cisplatin is based in the generation of reactive oxygen species, which interferes with the antioxidant protection of the organ of Corti. Conversely, the protection of the cochlea with antioxidants ameliorates the ototoxicity by cisplatin. The ototoxicity produced by cisplatin can be reversible or persistent, depending on the age of the patient, cumulative doses, number of chemotherapy cycles, history of noise exposure, and deteriorating renal function. We have obtained in rats an ototoxic chart utilizing cisplatin (10 mg/kg body weight injected intraperitoneally, once only). Together with this treatment, the animals were treated with melatonin in the drinking water (10 mg/L) or injected subcutaneously (250 microg), and with an antioxidant mixture, injected subcutaneously, composed of 0.25 mg alpha-tocopherol acid succinate, 3 mg ascorbic acid, 1 mg glutathione, and 60 mg N-acetylcysteine. The distortion product otoacoustic emissions were determined for a prolonged period of time for each animal. The ototoxicity produced by cisplatin was maximal from days 7 to 10 post-treatment, returning to normal values in a month. When melatonin and the antioxidant mixture were present, the recovery was between days 10 and 15 post-treatment, independent of the means of administration of the pineal product. We conclude that the ototoxicity caused by cisplatin is ameliorated by melatonin and other antioxidants.

An NMR-based metabonomic investigation of the toxic effects of 3-trifluoromethyl-aniline on the earthworm Eisenia veneta

1H NMR spectra of earthworms Eisenia veneta treated with 3-trifluoromethyl-aniline in a 72-h contact filter paper test have been analysed using pattern recognition techniques to determine the biochemical response. Various strategies for data reduction of the metabolite profile, and illustration by principal components analysis are applied and discussed. The use of mean principal components plots in simplifying group data representation and highlighting the dose-response function is demonstrated. Hierarchical cluster analysis, and cluster significance analysis of the principal components were also used to examine the relative distribution of dose groups. Identification and assignment of metabolite responses to toxicity were found via correlation coefficient-shift plots. As measured by the correlation coefficients alanine was the most significant metabolite, but increased levels of other amino acids such as glycine and asparagine were also observed. Further, elevated levels of glucose, and the citric acid cycle intermediates citrate and succinate were noted as potential biomarkers of toxicity. This work provides a basis for examining the biochemical response of invertebrates to toxins. This should provide a framework to examine toxicity effects of other halogenated aromatic pollutants to earthworms used as environmental monitors.

Selective involvement of reactive oxygen intermediates in platelet-activating factor-mediated activation of NF-kappaB.

Although it has been suggested that some biological activities of platelet-activating factor (PAF) are mediated by, at least in part, reactive oxygen intermediates (ROI), the precise mechanisms underlying the interaction between the two remains to be elucidated. Antioxidants, such as alpha-tocopherol acid succinate, N-acetyl-L-Cysteine, pyrrolidinedithiocarbamate failed to inhibit PAF-induced immediate systemic reactions such as lethality, symptoms of disseminated intravascular coagulation, and histological changes such as pulmonary edema and hemorrhage in renal medullae 10 min following PAF injection. In contrast. antioxidants significantly inhibited both the in vivo and in vitro PAF-induced NF-kappaB activation and NF-kappaB-dependent TNF-alpha expression. The effects of the antioxidants were due to their inhibition of PAF-induced degradation of IkappaBalpha, a protein responsible for keeping NF-kappaB in an inactive form. A protein tyrosine kinase and N-tosyl-L-phenylalanine chloromethyl ketone sensitive serine protease were involved in both PAF- and H2O2-induced NF-kappaB activation. Collectively, these data indicate that the PAF-induced NF-kappaB activation is selectively mediated through the generation of ROI.

Melatonin and other antioxidants prolong the postmortem activity of the outer hair cells of the organ of Corti: its relation to the type of death.

The outer hair cells of the organ of Corti transform sound into electrical signals, beginning the nervous auditive process. These cells produce acoustic emissions when working routinely, known as otoacoustic emissions. Otoacoustic emissions (OAEs) are recorded from the hearing duct through a probe which incorporates a sound source and a sensitive microphone. On the other hand, the cochlea produces oxygen-derived free radicals and nitric oxide, in addition, melatonin is present in the cochlea. The authors have studied the influence of melatonin or an antioxidant mixture (alpha-tocopherol acid succinate, ascorbic acid, glutathione, and N-acetylcysteine) on the postmortem activity of the outer hair cells of the organ of Corti of the rat, measuring distortion product otoacoustic emissions. Control rats showed postmortem distortion product otoacoustic emissions for about 2 min when sacrificed by decapitation, and for about 3 min when sacrificed by chloroform inhalation. Melatonin prolonged the postmortem activity 3.5 times when the animals were sacrificed by decapitation, and 7 times when animals were sacrificed by chloroform inhalation. Similar results were obtained with the antioxidant mixture. Results show that melatonin and other antioxidants have, in general, a protective role on the postmortem activity of the outer hair cells of the organ of Corti.

Dietary Vitamin E and β-Carotene Sources Influence Vitamin A and E Storage in Young Rats Fed Marginal and Adequate Vitamin E

The effects of two vitamin E levels (30 and 75 IU/kg diet) and the interrelation of two vitamin E sources [dl-α-tocopheryl acetate (dl-α-TA) and d-α-tocopheryl acid succinate (d-α-TAS)] and three vitamin A sources [retinyl palmitate (RP), all-trans synthetic β-carotene (SBC), and natural β-carotene (NBC)] were studied. Dietary vitamin A sources provided 4,000 IU/kg. Twelve groups of Fischer 344 rats (10/group) were fed designated diets for eight weeks. For RP, SBC, and NBC, the increase in each vitamin E source from a marginal to an adequate dietary level caused a significant increase in liver and heart α-tocopherol. Among rats fed diets with an adequate level of vitamin E, d-α-TAS was not as effective as dl-α-TA in increasing liver α-tocopherol levels. Plasma retinol was lower in rats fed d-α-TAS than in those fed dl-α-TA. Among rats fed diets with an adequate level of dl-α-TA, those fed SBC had significantly higher liver and heart α-tocopherol concentrations than did all other groups (p < 0.05). Liver retinol equivalents for rats fed NBC were approximately 66% lower than those in rats fed SBC or RP (p < 0.05). The roles of the two vitamin E sources in α-tocopherol metabolism are not equivalent. These data indicate that vitamin A source influences the magnitude of the tissue vitamin A and E changes in response to the two vitamin E sources.

Yeast influence on volatile composition of wines.

Nine Saccharomyces cerevisiae and four Saccharomyces bayanus strains used in the production of Trebbiano wine were examined. The aim of this study is to evaluate the different abilities of various yeast strains in wine-making. The possibility of yeast discrimination on the basis of their volatile production is another possibility. Wine chemical analyses showed statistically significant differences depending on the yeast strain used. Some compounds such as 2-phenylethanol, 2-phenethyl acetate, ethyl lactate, 3-ethoxypropanol, and, to a lesser extent, diethyl succinate and propionic acid characterized examined Saccharomyces bayanus yeasts. Moreover, these strains did not produce any undesirable compounds, such as acetic acid and sulfur anhydride. For these reasons and because they synthesized malic acid, they could be more suitable for white wine production. The other yeasts showed great differences, which are difficult to correlate with the strain. However, some strains had peculiar characteristics, such as an uncommonly high concentration of n-propanol and 3-ethoxypropanol.

Alpha-Tocopherol Derivatives in an Experimental Model of Filtering Surgery

Purpose: To evaluate the efficiency and reliability of α-tocopherol in an experimental model of glaucoma filtering surgery. Methods: Thirty pigmented rabbits were randomly divided into three study groups. Twenty-four hours before surgery, the animals were injected subconjunctivally with 0.5 ml of solution that depended on the group of treatment: group I (n = 10), 0.75% ethanol in balanced saline solution (BSS); group II (n = 10), 100 mg α-tocopherol acetate (ATA) in 0.75% ethanol in BSS; group III (n = 10), 100 mg α-tocopherol acid succinate (ATS) in 0.75% ethanol in BSS. The animals were followed during 30 days (intraocular pressure, IOP; filtering surgery; inflammatory reaction). Results: IOPs were significantly lower in the treatment groups (ATA and ATS) than in the control group from days 7 and 10, respectively, till the end of the study. On day 7, the mean IOP in the ATA group was 15.8 versus 22.1 mm Hg in the control group. On day 10, the mean IOP in the ATS group was 15 versus 22.78 mm Hg in the control group. Filtering blebs showed statistically significant differences between the control and treated groups from day 5 to day 16. Conclusions: α-Tocopherol (ATA and ATS) showed better IOP control and bleb survival in this experimental model of filtering surgery.

Liquid Chromatographic Determination of Carotenoids and Vitamins A and E in Multivitamin Tablets

Carotenoids and vitamins A and E in multivitamin tablets can be determined simultaneously by reversed-phased liquid chromatography (LC) with a programmable UV detector. Samples were dissolved in dimethyl sulfoxide and then extracted with hexane. A portion was injected onto a Symmetry C18, 150 x 4.6 mm id, 5 microns column and chromatographed with a mobile phase of acetonitrile--0.25% ammonium acetate in methanol and 0.05% triethylamine in dichloromethane. A step gradient was used. The system was operated at 25 degrees C with a flow rate of 1.5 mL/min. UV detection was at 325 nm for retinols, 285 nm for tocopherols, and 450 nm for carotenoids. Detection limits were less than 0.3 ng for retinol and retinyl acetate; 2 ng for alpha-tocopherol acid succinate; 10 ng for alpha-tocopherol, gamma-tocopherol, and alpha-tocopherol acetate; and 0.4 ng for alpha-carotene and beta-carotene. Intraday and interday coefficients of variation ranged from 1.40 to 5.20%. The sample preparation method and LC assay are practical for quality control and routine analysis of multivitamin tablets.

Effect of chemical structure on the solubility of antioxidants in supercritical carbon dioxide: experimental data and correlation

In this work, the solubility of natural and synthetic antioxidants in supercritical carbon dioxide is determined by a dynamic method in the pressure range 130–250 bar at 308.1–333.1 K. The compounds considered are ascorbic acid, ascorbyl palmitate, gallic acid, propyl gallate, lauryl gallate, α-tocopherol acid succinate and butyl hydroxyl anisole. The experimental data are correlated using the Peng–Robinson equation of state, and the solute properties are estimated by group contribution methods.

Morphological and histochemical ageing changes in patellar articular cartilage of the rat

The aim of this study was to investigate the variation in cartilage characteristics with age. Fresh-frozen cryostat sections of the patellar articular cartilage of the rat were used to demonstrate the enzyme activity of succinate dehydrogenase, lactate dehydrogenase, alkaline phosphatase, and acid phosphatase in the different layers and at different ages. Light microscopic techniques were used to analyse quantitative features such as thickness, cell density and the histological characteristics of the articular cartilage. The results indicate that cell density is significantly affected by age. Furthermore, it depends on the distance from the surface. The most marked decline in cell density occurred between months 3 and 6. The thickness of the articular cartilage also varies with age. The reduction in cartilage thickness was most striking between months 3 and 6. Differentiation into the histological layers is obvious after 3 months. Glycolytic enzymes were strongly reactive in all regions and at all ages, whereas aerobic activity declines with age. The metabolic and morphological changes in ageing cartilage contribute to trophic disorders and deterioration of the functional cartilaginous situation in adult cartilage.

Haemolysis of Human Erythrocytes by alpha -Tocopheryl Succinate

Alpha-tocopheryl acid succinate. when incubated at concentrations above 100 mg l - 1 with human red blood cells in a phosphate buffer pH 7.5, caused significant haemolysis of the cells. This effect appears to be unique to the succinate ester of alpha -tocopherol, since no haemolysis was observed under equivalent conditions with alpha -tocopherol itself, succinic acid or a range of other tocopherol compounds. Haemolysis was considerably reduced when the test solutions were deaerated before adding the tocopheryl succinate, which suggests the involvement of activated oxygen species in the lysis of the red blood cells. However, no activated oxygen species could be detected in the test solutions. When used as a dietary supplement, alpha -tocopheryl succinate should not cause haemolysis, since the ester is dissociated in the gut before absorption into the blood stream, and concentrations of alpha -tocopherol in the blood normally do not exceed 15 mg l- 1. Also, calcium and magnesium in blood serum were found to...

Modulation of TCDD-induced fetotoxicity and oxidative stress in embryonic and placental tissues of C57BL/6J mice by vitamin E succinate and ellagic acid

The ability of vitamin E succinate and ellagic acid to modulate 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD)-induced developmental toxicity and oxidative damage in embryonic/fetal and placental tissues was studied in C57BL/6J mice. Vitamin E succinate (100 mg/kg per day) and ellagic acid(6 mg/kg per day) were administered by gavage to groups of pregnant mice on days 10, 11 and 12 of gestation and 40 mg vitamin E succinate/kg or 3 mg ellagic acid/kg on day 13 of gestation. A number of animals from the vitamin E succinate and ellagic acid treated groups also received 30 μg TCDD/kg on day 12 of gestation, 2 h prior to vitamin E succinate or ellagic acid treatment. Groups of treated animals were terminated on day 14 of gestation, and the biomarkers of oxidative stress, including superoxide anion production and the induction of lipid peroxidation and DNA-single strand breaks (SSB), were determined in whole embryonic and placental tissues homogenates. Groups of treated animals were also killed on day 18 of gestation for investigation of the fetotoxic and teratogenic effects as well as effects on the placentae. Vitamin E succinate and ellagic acid significantly decreased TCDD-induced fetal growth retardation fetal death and placental weight reduction, with no significant ameliorating effects on TCDD-induced malformations including cleft palate and hydronephrosis. Vitamin E succinate treatment resulted in decreases of 77–88%, 70–87%, and 21–47% in the production of superoxide anion, lipid peroxidation and DNA-SSB, respectively, in embryonic and placental tissues, while ellagic acid caused 47–98%, 79–93%, and 37–53% decreases, respectively, in these parameters. These results indicate that TCDD-induced fetal death and fetal and placental weight reductions in C57BL/6J mice may be due to oxidative damage induced by TCDD, and ellagic acid and vitamin E succinate provide protection against those effects. Ellagic acid provided better protection than vitamin E succinate against TCDD-induced fetal growth retardation and increases in lipid peroxidation in embryonic and placental tissues.

Determination of Inorganic and Organic Anions in Beer and Wort by Capillary Electrophoresis

A rapid, easy, and reproducible method for the determination of inorganic and organic anions in beer and wort by capillary electrophoresis was developed. Three inorganic anions (chloride, sulfate, and phosphate) and nine organic acids (oxalate, formate, malate, citrate, succinate, pyruvate, acetate, lactate, and pyroglutamate) were separated and quantified in less than 7 min. Sample preparation was simple and consisted only of degassing the beer by sonication and 1:5 dilution with Milli Q water prior to injection. Satisfactory reproducibility was obtained, and the concentrations of anions were in good agreement with those found by conventional techniques.

Effect of vitamin E succinate on free radical formation, lipid peroxidation levels and cyclooxygenase activity in murine melanoma cells

Studies have suggested that the antitumour properties of vitamin E may lie in its ability to quench highly reactive free radicals. In this study supplementation of Murine melanoma (BL6) cells with 1–10μg/ml α-Tocopherol acid succinate (vitamin E succinate) resulted in a significant decrease in growth at 5, 7 and 10μg/ml respectively. BL6 cells supplemented with 5, 7 and 10μg/ml vitamin E succinate produced significant increases in lipid peroxidation (as measured by malondialdehyde levels), while free radical levels were significantly increased at vitamin E succinate concentrations of 7 and 10μg/ml respectively. The cyclooxygenase activity in BL6 cells supplemented with 1–10μg/ml vitamin E succinate showed a similar trend to that observed for free radical and lipid peroxidation experiments with a significant increase in enzyme activity occurring at 7 and 10μg/ml respectively. Addition of indomethacin (cyclooxygenase inhibitor) to BL6 cells, resulted in a non-significant decrease in cyclooxygenase activity at 3, 5, 7 and 10μg/ml vitamin E succinate when compared to control cultures 0E. This decrease in cyclooxygenase activity was inversely related to BL6 cell growth and correlated with a significant decrease in lipid peroxidation levels. The levels of free radicals on the other hand were neither increased or decreased when compared to control cultures. Comparison of free radical levels in indomethacin treated to untreated cultures, however, showed a marked decrease in free radical levels in indomethacin treated cells. Results from these studies suggest that the growth inhibitory effects of vitamin E succinate on BL6 cell growth may be due to its direct effect on the activity of the cyclooxygenase enzyme and furthermore, that a relationship exists between cyclooxygenase enzyme activity and the levels of the free radicals and lipid peroxidation within the cells.

Effect of α-Tocopherol Succinate on Free Radical and Lipid Peroxidation Levels in BL6 Melanoma Cells

Numerous studies have proposed a radical or oxidant involvement in a number of degenerative diseases such as cancer. This has led to suggestions that the supplementation of antioxidants such as α-tocopherol (vitamin E) may function to reduce the growth of cancer. In this study, a nonmalignant Monkey kidney (LLCMK) and a malignant Murine melanoma (BL6-F10) cell line were supplemented with varying levels of α-Tocopherol acid succinate (vitamin E succinate) ranging from 1 to 10 μg/ml. BL6-F10 cells supplemented with 5, 7, and 10 μg/ml vitamin E succinate, showed significant decreases in cell proliferation, and this decrease was accompanied by a concomitant increase rather than a decrease in the levels of free radicals and lipid peroxidation. LLCMK cells supplemented with 1–10 μg/ml vitamin E succinate showed no significant increase or decrease in growth, while the levels of lipid peroxidation were shown to be insignificantly elevated at 5, 7, and 10 μg/ml vitamin E succinate. Free radical levels in LLCMK cells were significantly decreased at 1 μg/ml vitamin E succinate, while at 3, 5, 7, and 10 μg/ml supplementary vitamin E succinate, free radical levels increased compared to the 1 μg/ml group, but not compared to control cultures. These results suggest that the inhibitory effects of vitamin E succinate on BL6-F10 cell growth in vitro is not a consequence of its antioxidant properties, but may, in fact, be due to one or more of its other potential roles within the cells, such as the regulation of cellular enzyme activities involved in growth. © 1997 Elsevier Science Inc.

Scanning electron microscopy, whole-mount histology, and histochemistry of two anodontine glochidia (Bivalvia: Unionidae)

Intramarsupial glochidia of Anodonta anatina (L.) and Pseudanodonta complanata (Rossmässler) were studied in southern Finland. Material staining positively with periodic acid – Schiff's reagent (PAS), neutral lipid reserves, and acid phosphatase activity have different distributions in the mantle of the two species. Moreover, the mucous covering of the mantle of the two glochidia behaves differently on critical-point drying. The presence of microvilli with alkaline phosphatase activity on the mantle surface and acid phosphatase activity in the mantle cells in both glochidia suggest that the mantle plays a role in nutrient uptake and digestion and possibly also in electrolyte uptake. The primordia of the stomach, digestive diverticula, and intestine, at least in A. anatina glochidia, contain neutral lipids and exhibit acid phosphatase activity: In A. anatina glochidia, a microvillous layer with alkaline phosphatase activity continues from the ventral walls of the lateral pits to the suspected kidney diverticula. In both glochidia, there may be three pairs of rudimentary ganglia, which do not stain with methylene blue. The eight ciliated sense organs of the glochidia are methylene blue- and PAS-positive and they exhibit succinate dehydrogenase and acid phosphatase activity. In each mantle lobe, the enveloping cell of the dorsal ciliary organ is interconnected with those of the ventral triad via a cellular fold or "tract," and the ciliated central cells of the organs send axons towards each other.

The role of adenylate cyclase, cAMP and PGE 2 in the in vitro growth regulation of murine melanoma cells by vitamin E

Previous studies have shown that vitamin E supplementation inhibits murine melanoma cell growth in vitro. In this study, malignant murine melanoma (BL6) and non-malignant monkey kidney (LLCMK) cells were supplemented with 1–10 μg/ml d-α-tocopherol acid succinate (vitamin E succinate). The effect of vitamin E succinate supplementation on growth as well as the levels of adenylate cyclase activity, prostaglandin E 2 (PGE 2) and cyclic adenosine monophosphate (cAMP) were determined in these cells. Results from these studies indicated a significant inhibition of BL6 cell growth at 5 ( P < 0.025), 7 and 10 μg/ml ( P < 0.001) vitamin E succinate supplementation, while LLCMK cells showed no significant increase or decrease in growth following vitamin E succinate supplementation. BL6 cells supplemented with 7 and 10 μg/ml vitamin E succinate showed a marked increase in PGE 2 levels, with a significant increase ( P < 0.025) occurring at 10 μg/ml. Adenylate cyclase activity in BL6 cells was also significantly increased at vitamin E succinate concentrations of 7 ( P < 0.05) and 10 μg/ml ( P < 0.05), respectively, and supplementation of these cells with 5 ( P < 0.05), 7 and 10 μg/ml ( P < 0.001) vitamin E succinate resulted in a significant increase in the levels of cAMP, while LLCMK cells showed no significant increase or decrease in PGE 2, adenylate cyclase activity or cAMP levels over the vitamin concentrations tested.

Effects of alpha-tocopherol and beta-carotene on hepatic lipid peroxidation and blood lipids in rats with dietary iron overload.

The ability of dietary antioxidants to reduce lipid peroxidation induced by iron overload was examined in weanling male Sprague-Dawley rats. Animals were fed ad libitum a modified AIN-76A diet (control) or control diet with 0.5% alpha-tocopherol acid succinate, 0.5% crystalline trans-beta-carotene, or 0.5% alpha-tocopherol acid succinate + 0.5% trans-beta-carotene for four weeks. In the following four-week period, the animals received the above diets with 10,000 micrograms Fe/g; a control group continued to receive 35 micrograms Fe/g, and a high-iron group received 10,000 micrograms Fe/g with no antioxidants. After four weeks of dietary supplementation with alpha-tocopherol. Beta-carotene or alpha-tocopherol + beta-carotene, liver concentrations of alpha-tocopherol and beta-carotene increased significantly (p < 0.001). Liver lipid peroxidation, measured by the lipid-conjugated diene assay, increased significantly from 0.012 mumol/mg of lipid in the controls to 0.021 mumol/mg of lipid in animals receiving the high-iron diet. However, lipid peroxidation was significantly reduced in all animals fed the antioxidants, with the group fed alpha-tocopherol + beta-carotene having a lower level than the high-iron group. Total serum cholesterol was elevated in animals fed a high-iron diet and in animals fed the high-iron diet with alpha-tocopherol. In contrast, total serum cholesterol levels in the two groups of animals receiving the diets containing high iron with beta-carotene alone or high iron with beta-carotene + alpha-tocopherol were significantly reduced to the level of the control group. High-density lipoprotein cholesterol also decreased to baseline in the animals receiving beta-carotene alone. Modulation of lipid peroxidation by alpha-tocopherol or beta-carotene may be an important mechanism for reducing oxidative stress.

Naphthalene-induced oxidative stress in rats and the protective effects of vitamin E succinate

Quinone metabolites of naphthalene (NAP) are known to produce lipid peroxidation. However, the ability of naphthalene to induce oxidative stress in experimental animals has not been extensively investigated. Furthermore, the effects of vitamin E succinate [(+)-a-tocopherol acid succinate; Veson naphthalene-induced oxidative stress and tissue damage were assessed. Female Sprague-Dawley rats were treated with a single oral dose of 1100 mg naphthalene/kg (0.50 LD SO) in corn oil. Vitamin E succinate-treated rats received 100 mg VES/kg/day orally for 3 d before naphthalene treatment, and 40 mg VES/kg/d after NAP administration. Hepatic and brain tissues and urine samples were collected 0, 12, 24, 48, and 72 h after NAP treatment. Naphthalene treatment resulted in a 2.1-fold increase in lipid peroxidation in liver and brain mitochondria at the 24-h time point. Increases in hepatic and brain mitochondrial lipid peroxidation in VES plus NAP-treated rats were 39–46% less than NAP treated rats at 24 h. DNA-single strand breaks increased 3.0-fold in hepatic tissues in NAP treated rats, and increased only 1.6-fold in VIES protected rats at the 24-h time point. Glutathione (GSH) decreased by 83 and 49% in hepatic and brain tissues, respectively, in NAP-treated rats at the 24-h time point, while GSH content in VES plus NAP-treated rats decreased 47 and 21% in hepatic and brain tissues, respectively, at this same time point. Microsomal membrane fluidity, a measurement of membrane damage, increased 1.9- and 1.7-fold in liver and brain tissues, respectively, in NAPtreated rats, and only 1.3- and 1.2-fold in NAP plus VES-treated rats at the 24-h time point. The urinary excretion of malondialdehyde (MDA), formaldehyde (FA), acetaldehyde (ACT), and acetone (ACON) was determined at 096 h after NAP administration. Between 12–24 h after NAP administration maximal excretion of the four urinary lipid metabolites was observed, with increases of 4.5-, 2.7-, 2.3-, and 2.8-fold for MDA, FA, ACT, and ACON, respectively, at the 24-h time point. VES reduced the NAP-induced excretion of these urinary metabolites by 2849% 24 h after NAP administration. These results support the hypothesis that NAP induces oxidative stress and tissue damage, and that vitamin E succinate provides significant protection.

The mae1 gene of Schizosaccharomyces pombe encodes a permease for malate and other C4 dicarboxylic acids.

The mae1 gene of the yeast Schizosaccharomyces pombe was identified on the basis of its ability to complement a mutant defective in the transport of malic acid. Analysis of the DNA sequence revealed an open reading frame of 1314 base pairs, encoding a polypeptide of 438 amino acids with a predicted molecular weight of 49 kDa. A hydropathy profile of the predicted amino acid sequence revealed a protein with ten membrane-spanning or associated domains and hydrophilic N- and C- termini. The predicted secondary structure of the protein in similar to models proposed for other integral membrane proteins from both prokaryotes and eukaryotes. The S. pombe mae1 gene encodes a single mRNA of 1.5 kb. The mea1 gene is expressed constitutively and is not subject to catabolite repression as was previously reported for the malate permease systems of Candida utilis and Hansenula anomala. The mae1 gene was mapped 2842 bp 5' to the MFml gene on chromosome I. Transport assays revealed that the mae1 gene encodes a permease involved in the uptake of L-malate, succinate and malonic acid.