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PubMedDate not supplied

Utilization of the insulin-signaling network in the metabolic actions of alpha-lipoic acid-reduction or oxidation?

Alpha-lipoic acid is a naturally occurring cofactor of mitochondrial dehydrogenase complexes and a potent antioxidant. It can interchange between a reduced form and an oxidized form, thereby displaying reducing (antioxidant) and prooxidant properties, respectively. It is suggested that alpha-lipoic acid through its prooxidant properties acutely stimulates the insulin-signaling cascade, thereby increasing glucose uptake in muscle and fat cells. On the other hand, alpha-lipoic acid appears to protect the insulin-signaling cascade from oxidative stress-induced insulin resistance through its reducing capacities. In addition, alpha-lipoic acid seems to inhibit hepatic gluconeogenesis by interfering with fatty acid oxidation, as well as to increase peripheral glucose utilization by activating pyruvate dehydrogenase resulting in increased glucose oxidation. These different properties render alpha-lipoic acid a potentially attractive therapeutic agent for the treatment of insulin resistance. Moreover, given the potential role of oxidative stress in the pathogenesis of secondary complications in diabetes, alpha-lipoic acid might be beneficial in the prevention/treatment of these complications as was recently shown for diabetic neuropathy.

Animals↗
PubMed1995

Reduction of oxidative DNA-damage in humans by brussels sprouts.

The effect of consumption of Brussels sprouts on levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in human urine was investigated in 10 healthy, male, non-smoking volunteers. Following a 3 week run-in period, five volunteers continued on a diet free of cruciferous vegetables for a subsequent 3 week intervention period (control group), while the other five (sprouts group) consumed 300 g of cooked Brussels sprouts per day, at the expense of 300 g of a glucosinolate-free vegetable. Levels of 8-oxodG in 24 h urine samples were measured by HPLC. In the control group there was no difference between the two periods in levels of 8-oxodG (P = 0.72). In contrast, in the sprouts group the levels of 8-oxodG were decreased by 28% during the intervention period (P = 0.039). The present findings support the results of epidemiologic studies that consumption of cruciferous vegetables may result in a decreased cancer risk.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2005

Reduction of oxidative changes in human spermatozoa by exogenous gangliosides.

The effect of exogenous gangliosides, the sialic acid-containing glycosphingolipids, on oxidative changes in human spermatozoa was investigated. The incorporation of disialogangliosides or trisialogangliosides (GD1b and GT1b, respectively) into the iron/ascorbate promoter system for induction of lipid peroxidation decreased the release of malondialdehyde (MDA) from peroxidizing spermatozoa. The application of monosialogangliosides and disialogangliosides (GM1 and GD1a, respectively) did not have any effect under identical experimental conditions. GT1b, at a micromolar concentration, significantly inhibited the production of MDA, a breakdown product of lipid peroxide decomposition in spermatozoa of normozoospermic infertile men (P < 0.001; n = 51). An enhanced generation of MDA exhibited by the sperm population from the low-density Percoll fraction containing defective and/or immature spermatozoa was significantly reduced in the presence of GT1b. These results and the experiments on the influence of iron-chelating agent ethylenediamine tetraacetic acid (EDTA) as well as ferrous ion concentration itself on lipid peroxidation support the hypothesis that the protective effect of ganglioside against MDA generation could be the result of its chelating activity. Furthermore, superoxide anion release of phorbol myristate acetate-stimulated spermatozoa was significantly reduced in the presence of 50 and 100 micromol l(-1) GD1b (P < 0.05) and GT1b (P < 0.005). The inhibitory effect of 100 micromol l(-1) GT1b on spermatozoa from infertile normozoospermic men was statistically significant (P < 0.001; n = 21) and did not depend on the initial superoxide anion production. In conclusion, the protective action of GD1b and GT1b could be related to both scavenging of free radicals and metal-chelating properties, which might have relevance in the protection against oxidation-induced processes in human spermatozoa.

Gangliosides↗
PubMed2006

Site-specific reduction of oxidative and lipid metabolism in adipose tissue of 3'-azido-3'-deoxythymidine-treated rats.

Although it is well accepted that treatment with some nucleoside reverse transcriptase inhibitors modifies both fat metabolism and fat distribution in humans, the mechanisms underlying these modifications are not yet known. The present investigation examined whether a decrease in oxidative capacity, induced by a chronic oral administration of 3'-azido-3'-deoxythymidine (AZT) in rats, could be associated with an alteration of the lipogenic capacity of white adipose tissues. The impact of obesity as a factor was then evaluated. Results showed that AZT treatment induced differential effects depending on anatomical localization. Indeed, in the inguinal adipose tissue, the specific activities of cytochrome c oxidase and fatty acid synthase, two rate-controlling enzymes in energy and lipogenic metabolisms, respectively, both decreased under AZT treatment, thus leading to a lowered cell lipid accumulation. Moreover, the AMP-activated protein kinase phosphorylation level tended to increase, thus implying that AZT causes an energy imbalance. Furthermore, the inguinal tissue of obese rats presented a sensitivity to AZT treatment that was higher than that of lean rats. In contrast, for epididymal tissue, no significant change in all these parameters could be detected under AZT treatment, regardless of the nutritional status of the animals. Taken together, these data demonstrate differential effects of AZT on subcutaneous adipose tissue and visceral white adipose tissue. It could be considered that the chronic decreases in energy and lipogenic metabolism of inguinal adipocyte, consecutive to AZT treatment, may lead, in the long term, to adipose tissue atrophy.

Adipose Tissue↗
PubMed1984

Microbial models of mammalian metabolism: microbial reduction and oxidation of pentoxifylline.

Fourteen microorganisms, including fungi, yeasts, and bacteria, were screened for their ability to metabolize the xanthine drug pentoxifylline. Thirteen cultures either reduced the drug to the alcohol metabolite or oxidatively cleaved the ketonic side chain to homologous carboxylic acid metabolites. The alcohol metabolite was the predominant or sole metabolite in all organisms, with conversions ranging from 6 to 91%. Preparative-scale production of the alcohol metabolite with Rhodotorula rubra (ATCC 20129) allowed for the isolation of this product with a 40% yield. Two organisms also produced the carboxylic acid metabolites at low levels (2 to 10%). The routes of metabolism in microbial cultures are the same as those reported in mammalian systems.

Animals↗
PubMed1978

Developmental changes in the enzymatic capacity for reduction and oxidation of alpha-ketoadipate in rat liver, heart, kidney, and brain.

alpha-Ketoadipate, an intermediate common to lysine and tryptophan metabolism, is a substrate for both alpha-ketoadipate reductase (alpha-KAR) and alpha-ketoadipate dehydrogenase (alpha-KADH). A comparison was made of the activities of these two enzymes in liver, heart, kidney, and brain of rats during the period from 5 days before birth to 56 days after birth. In general, both enzymes increased in activity during development in all tissues tested; however, different patterns of increase were observed (Figs. 1 and 2). The ratio of alpha-KADH to alpha-KAR (on the basis of activity/g tissue) did not change significantly in liver until day 10 and then increased 6.6-fold (from 0.08 to 0.53) in the period from day 10 to day 28. For other tissues the ratios increased 5.5-fold in hearts (from 0.2 to 1.1), 12-fold in kidney (from 0.2 to 2.4), and 5.3-fold in brain (from 0.3 to 1.6) during the period from day -5 to day 56. These results suggest that alpha-KAR has a major role in the metabolism of lysine and tryptophan during development.

Adipates↗
PubMed2004

Lignin-stimulated reduction of oxidative DNA lesions in testicular cells and lymphocytes of sprague-dawley rats in vitro and ex vivo.

Lignin biopolymers constitute 30% of plant biomass and belong to the most abundant organic polymers on earth. We showed previously that this important component of dietary fiber exhibited a protective effect against the overall DNA damage induced by H2O2 or N-methyl-N'-nitro-N-nitrosoguanidine in hamster lung cells and human foreskin cells cultured in vitro. The objective of the present work was to examine DNA-protective effects of lignin in rat testicular cells and rat peripheral blood lymphocytes using in vitro and ex vivo experiments. H2O2 and visible light-excited methylene blue (MB) were used as DNA-damaging agents. Testicular cells were chosen because the germinal epithelium of testes is one of the most proliferately active tissues potentially susceptible to DNA-damaging effects. As a second target peripheral blood lymphocytes were chosen because dietary lignin or its metabolites circulate in the animal organism probably through the blood system. For the in vitro experiments, isolated cells were preincubated with lignin for 2 h before treatment with one of the oxidative agents. In ex vivo experiments, the cells were exposed to H2O2 or visible light-excited MB after isolation from rats fed either a common diet or a lignin-supplemented diet. The water-soluble, sulfur-free lignin used in experiments was obtained by fractionation of hardwood hydrolysate. The level of direct single-strand DNA breaks in H2O2-treated cells was measured by the classical comet assay, and the level of oxidative DNA lesions in visible light-treated cells was measured by a modified comet assay. We found that lignin reduced DNA lesions induced by H2O2 or visible light-excited MB both in vitro and ex vivo. The major conclusion of our study is that lignin polymer obtained by fractionation of hardwood hydrolysate manifested a specific type of antimutagenic effect.

Animals↗
PubMed2005

Abiotic dealkylation and hydrolysis of atrazine by birnessite.

Atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine) and its degradation products are important contaminants of world water systems and have effects on aquatic life. These effects are modulated by the degradation of atrazine, which depends, in part, on its reactivity with soil minerals. We have studied the degradation reaction of atrazine on synthetic birnessite (delta-MnO2) in the aqueous phase using a batch reactor and a developed high-performance liquid chromatography method. The reaction was studied in the absence of light at 25 degrees C and between pH 2.3 to pH 8.3. The reaction rates increased with decreasing pH and increasing delta-MnO2 loading, and they did not follow simple first-order kinetics. The major products are hydroxylated and mono- and didealkylatrazine. Ammeline and cyanuric acid also were detected. The half-life (t 1/2) for the degradation of atrazine was approximately 16.8 d and independent of oxygen. Manganese(II) evolution was a minor product. The mechanism of dealkylation involved proton transfer to Mn(IV)-stabilized oxo and imido bonds, with no net oxidation and reduction. Oxidation was a secondary reaction. The proposed abiotic pathway for the transformation of atrazine on delta-MnO2 was identical to the reported biotic pathway. Thus, delta-MnO2, a common soil component, facilitated the efficient N-dealkylation and hydrolysis of the herbicide atrazine at 25 degrees C, possibly via a nonoxidative mechanisms. The N-dealkylation has been attributed strictly to a biological process in soils.

Atrazine↗
PubMed1970

Reductive and oxidative biosynthesis of plasmalogens in myelinating brain.

Palmitic acid-1-(14)C and hexadecanol-1-(14)C were administered intracerebrally to 18-day-old rats. Incorporation of radioactivity into the constituent alkyl, alk-1-enyl, and 1-acyl moieties, as well as into the 2-acyl moieties, of the ethanolamine phosphatides of brain was determined after 1, 2, 3, 6, and 22 hr. Incorporation of radioactivity from hexadecanol into both alkyl ethers and alk-1-enyl ethers proceeded at a rate more than 10 times higher than from palmitic acid. Hexadecanol was rapidly oxidized to fatty acids which were incorporated into the acyl moieties of the ethanolamine phosphatides. When palmitic acid was used as a precursor, labeled long-chain alcohols could be isolated from the lipid extract. As labeled long-chain aldehydes could not be detected in any of the lipid extracts, alcohols appear to be key intermediates for the biosynthesis of both alkyl and alk-1-enyl glycerophosphatides.

Alcohols↗