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Aalt Bast

Publications and source records attributed to Aalt Bast.

52 records · Page 3Linked to original sources
PubMed2003

Inhibition of various glutathione S-transferase isoenzymes by RRR-alpha-tocopherol.

The activity of human cytosolic glutathione S-transferases (GSTs) can positively or negatively be changed by various compounds. It is for instance known that RRR-alpha-tocopherol inhibits GST P1-1 [Haaften van R.I.M. et al. (2001) Alpha-tocopherol inhibits human glutathione S-transferase pi. BBRC 280, 631-633]. The effect of RRR-alpha-tocopherol on the other isoenzymes of GST in purified forms of the isoenzymes and in human liver cytosol (GST M and GST A) and lysate of human erythrocytes (GST P) is studied. It is found that all isoenzymes (purified enzymes and enzymes present in homogenates) are inhibited, in a concentration-dependent way, by RRR-alpha-tocopherol. GST P is in both cases inhibited with the highest potency compared to the other isoenzymes. It also appeared that the purified GST P1-1 isoenzyme is non-competitively inhibited by RRR-alpha-tocopherol. The IC(50) values of RRR-alpha-tocopherol for the purified isoenzymes of GST are much lower compared to the IC(50) values for human lysate and human liver cytosol. This is probably due to binding of RRR-alpha-tocopherol to proteins, e.g. albumin and hemoglobin, with higher affinity than to GST; so more RRR-alpha-tocopherol is needed to inhibit the enzyme. However, the inhibition of GSTs by RRR-alpha-tocopherol can still be of physiological relevance, because due to dermal application of cosmetic products very high concentrations vitamin E can be reached in the skin, where GST P1-1 is present. RRR-alpha-tocopherol might also be a good lead compound for the development of a new class of inhibitors of GST that can be used as adjuvant in cancer therapy.

Adult↗
PubMed2003

Using a correction factor to correct for overreporting in a food-frequency questionnaire does not improve biomarker-assessed validity of estimates for fruit and vegetable consumption.

To correct for overreporting of fruit and vegetable (FV) consumption in a food-frequency questionnaire, summary questions about consumption of main FV groups are often used to calculate correction factors. This study compared the ability to rank people according to their FV intake of those summary questions and the sum of questions on individual FV items within categories, and of corrected or uncorrected estimates of specific sorts of FV. Healthy middle-age women (n = 161) completed a food-frequency questionnaire about FV consumption during the previous month and gave a single fasting blood sample. Correction factors were calculated as the reported frequency on a summary question divided by the summed frequencies of all items in a category. Plasma carotenoids and vitamin C served as biomarkers of FV consumption. Significant correlations between FV consumption and biomarkers were observed (e.g., Spearman's correlation coefficient r with total carotenoids/vitamin C: 0.32/0.34 for vegetables, 0.30/0.25 for fruits). Summary estimates of cooked, raw and total vegetable consumption correlated higher with biomarkers than sum estimates. For fruits no differences in correlations between sum and summary estimates were observed. Applying a correction factor on the consumption of carrots and total cabbage resulted in lower correlations with relevant biomarkers. For broccoli/cauliflower, Brussels sprouts and citrus fruits, correlations with biomarkers did not change after correction. We conclude that summary questions may suffice to rank individuals according to their intake of main FV categories, and that correction for overreporting of individual FV items is probably not advisable when ranking individuals according to intake of these items.

Adult↗
PubMed2002

Oxidative damage shifts from lipid peroxidation to thiol arylation by catechol-containing antioxidants.

Catechol-containing antioxidants are able to protect against lipid peroxidation by nonenzymatic scavenging of free radicals with their catechol moiety. During their antioxidant activity, catechol oxidation products such as semiquinone radicals and quinones are formed. These oxidation products of 4-methylcatechol inactivate the GSH-dependent protection against lipid peroxidation and the calcium sequestration in liver microsomes. This effect is probably due to arylation by oxidation products of 4-methylcatechol of free thiol groups of the enzymes responsible for the GSH-dependent protection and calcium sequestration, i.e. the free radical reductase and calcium ATPase. It is concluded that a catechol-containing antioxidant might shift radical damage from lipid peroxidation to sulfhydryl arylation.

Animals↗
PubMed2002

The antioxidant activity of phloretin: the disclosure of a new antioxidant pharmacophore in flavonoids.

Phloretin is a dihydrochalcone flavonoid that displays a potent antioxidant activity in peroxynitrite scavenging and the inhibition of lipid peroxidation. Comparison with structurally related compounds revealed that the antioxidant pharmacophore of phloretin is 2,6-dihydroxyacetophenone. The potent activity of 2,6-dihydroxyacetophenone is due to stabilisation of its radical via tautomerisation. The antioxidant pharmacophore in the dihydrochalcone phloretin, i.e., the 2,6-dihydroxyacetophenone group, is different from the antioxidant pharmacophores previously reported in flavonoids.

Acetophenones↗
PubMed2002

Hypochlorous acid is a potent inhibitor of acetylcholinesterase.

The role of hydrogen peroxide and peroxynitrite in the induction of airway hyperreactivity has been well described. Another reactive species which is formed during airway inflammation is hypochlorous acid (HOCl). In the present investigation the effect of HOCl on cholinergic innervation of the airway was investigated. It was observed that HOCl was capable of increasing the basal tension of electrically stimulated tracheal smooth muscle. It was found that HOCl inhibits purified acetylcholinesterase with an IC50 value of 0.66 microM. Decreased acetylcholinesterase activity could allow accumulation of acetylcholine and increased airway muscle tension. The effects of HOCl on the isolated organ and the enzyme preparation could be precluded with thiol group-containing compounds such as reduced glutathione and N-acetylcysteine. The present findings indicate that HOCl can act as inhibitor of acetylcholinesterase. The implications of this finding for the induction of airway hyperreactivity are discussed.

Acetylcholinesterase↗
PubMed2002

Interactions between flavonoids and proteins: effect on the total antioxidant capacity.

Flavonoids are potent antioxidants. It is also known that flavonoids bind to proteins. The effect of the interaction between tea flavonoids and proteins on the antioxidant capacity was examined. Their separate and combined antioxidant capacities were measured with the Trolox equivalent antioxidant capacity (TEAC) assay. It was observed that the antioxidant capacity of several components of green and black tea with alpha-, beta-, and kappa-casein or albumin is not additive; that is, a part of the total antioxidant capacity is masked by the interaction. This masking depends on both the protein and the flavonoid used. Components in green and black tea, which show the highest masking in combination with beta-casein, are epigallocatechin gallate and gallic acid. The results demonstrate that the matrix influences the efficacy of an antioxidant.

Animals↗
PubMed2002

Exercise-induced oxidative stress in older adults as a function of habitual activity level.

OBJECTIVES: It has been suggested that regular physical activity might maintain and promote the antioxidant defense capacity against oxidative stress. Therefore, we assessed exercise-induced oxidative stress in relation to habitual physical activity level (PAL) in older adults. DESIGN: The study included a 2-week observation period for the measurement of average daily metabolic rate (ADMR) and PAL. Exercise-induced oxidative stress was measured during a 45-minute cycling test at submaximal intensity. SETTING: A university medical research center. PARTICIPANTS: Twenty-six subjects volunteered for the study (n = 26; mean age +/- standard deviation 60 +/- 1; body mass index 27 +/- 1 kg/m2). MEASUREMENTS: PAL was determined as ADMR combined with a measurement of basal metabolic rate (BMR): PAL = ADMR/BMR. ADMR was measured over 2 weeks with the doubly labeled water method, preceded by a BMR measurement with a ventilated hood. Antipyrine oxidation was used as marker for oxidative stress in vivo. Reaction of antipyrine with hydroxyl radicals results in the formation of para-hydroxyantipyrine (p-APOH) and ortho-hydroxyantipyrine (o-APOH), where o-APOH is not formed through alternative oxygenetic pathways. RESULTS: PAL was inversely related to the exercise-induced increase in the ratio of o-APOH to native antipyrine (r = 0.49, P = .010). The relationship between PAL and exercise-induced increase in the ratio of p-APOH (r = 0.30, P = .140) or thiobarbituric acid reactive species (r = 0.31, P = .130) did not reach the level of significance. CONCLUSION: Physically active older adults have a reduced exercise-induced oxidative stress than older adults with a lower level of physical activity. It seems that regular physical activity improves the antioxidant defense capacity.

Aged↗
PubMed2002

Protection of flavonoids against lipid peroxidation: the structure activity relationship revisited.

The inhibition of the lipid peroxidation, induced by iron and ascorbate in rat liver microsomes, by phenols and flavones was studied. The activity of phenol was enhanced by electron donating substituents, denoted by the Hammett sigma (sigma). The concentration of the substituted phenols giving 50% inhibition (IC50) of lipid peroxidation gave a good correlation with the sigma of the substituent (ln(1/IC50) = -8.92sigma + 5.80 (R = 0.94, p < 0.05)). In flavones two pharmacophores for the protection against lipid peroxidation were pinpointed: (i) a catechol moiety as ring B and (ii) an OH-group at the 3 position with electron donating groups at the 5 and/or 7 position in the AC-ring. An example of a flavone with the latter pharmacophore is galangin (3,5,7-trihydroxyflavone) where the reactivity of the 3-OH-group is enhanced by the electron donating effect of the 5- and 7-OH-groups. This is comparable to the effect of electron donating substituents on the activity of phenol. The prooxidant activity of flavones has been related to a low half peak oxidation potential (Ep/2). All flavones with a catechol as ring B have very low Ep/2, suggesting that they display a prominent prooxidant activity. In contrast, the Ep/2 varies within the group of flavones with a 3-OH, e.g. TUM 8436 (5,7,3',4'-tetra-O-methyl-quercetin) has a relatively high Ep/2 and is an excellent protector against lipid peroxidation. Apparently amongst the flavones with the pharmacophore in the AC-ring there are good antioxidants that are expected to display no or limited prooxidant properties.

Animals↗
PubMed2002

Tocotrienols inhibit human glutathione S-transferase P1-1.

Tocopherols and tocotrienols are food ingredients that are believed to have a positive effect on health. The most studied property of both groups of compounds is their antioxidant action. Previously, we found that tocopherols and diverse tocopherol derivatives can inhibit the activity of human glutathione S-transferase P1-1 (GST P1-1). In this study we found that GST P1-1 is also inhibited, in a concentration-dependent manner, by alpha- and gamma-tocotrienol. The concentration giving 50% inhibition of GST P1-1 is 1.8 +/- 0.1 microM for alpha-tocotrienol and 0.7 +/- 0.1 microM for gamma-tocotrienol. This inhibition of GST P1-1 is noncompetitive with respect to both substrates CDNB and GSH. We also examined the 3D structure of GST P1-1 for a possible tocopherol/tocotrienol binding site. The enzyme contains a very hydrophobic pit-like structure where the phytyl tail of tocopherols and tocotrienols could fit in. Binding of tocopherol and tocotrienol to this hydrophobic region might lead to bending of the 3D structure. In this way tocopherols and tocotrienols can inhibit the activity of the enzyme; this inhibition can have far-reaching implications for humans.

Antioxidants↗
PubMed2002

Effects of oral administration of N-acetyl-L-cysteine: a multi-biomarker study in smokers.

N-Acetyl-L-cysteine (NAC) has been shown to exert cancer-protective mechanisms and effects in experimental models. We report here the results of a randomized, double-blind, placebo-controlled, Phase II chemoprevention trial with NAC in healthy smoking volunteers. The subjects were supplemented daily with 2 x 600 mg of oral tablets of NAC (n = 20) or placebo (n = 21) for a period of 6 months, and internal dose markers [plasma and bronchoalveolar lavage (BAL) fluid cotinine, urine mutagenicity], biologically effective dose markers [smoking-related DNA adducts and hemoglobin (Hb) adducts], and biological response markers (micronuclei frequency and antioxidants scavenging capacity) were assessed at both pre- and postsupplementation times (T(0) and T(1), respectively). Overall, the internal dose markers remained unchanged at T(1) as compared with T(0) in both NAC and placebo groups. When quantifying the biologically effective dose markers, we observed an inhibitory effect of NAC toward the formation of lipophilic-DNA adducts (5.18 +/- 0.73 versus 4.08 +/- 1.03/10(8) nucleotides; mean +/- SE; P = 0.05) as well as of 7,8-dihydro-8-oxo-2'-deoxyguanosine adducts in BAL cells (3.9 +/- 0.6 versus 2.3 +/- 0.2/10(5) nucleotides; P = 0.003). There was no effect of NAC on the formation of lipophilic-DNA adducts in peripheral blood lymphocytes or polycyclic aromatic hydrocarbon-DNA adducts in mouth floor/buccal mucosa cells or 4-aminobiphenyl-Hb adducts. Likewise, quantification of the biological response markers showed an inhibitory effect of NAC on the frequency of micronuclei in mouth floor and in soft palate cells (1.3 +/- 0.2 versus 0.9 +/- 0.2; P = 0.001) and a stimulating effect of NAC on plasma antioxidant scavenging capacity (393 +/- 14 versus 473 +/- 19 microM Trolox; P = 0.1) but not on BAL fluid antioxidant scavenging capacity. We conclude that NAC has the potential to impact upon tobacco smoke carcinogenicity in humans because it can modulate certain cancer-associated biomarkers in specific organs.

Acetylcysteine↗
PubMed2002

Decreased redox state in red blood cells from patients with sarcoidosis.

BACKGROUND AND AIM OF THE WORK: The glutathione system has a key role in the defence against oxidative stress. To function properly, this system needs NADPH to maintain glutathione (GSH) in its reduced form. We hypothesized that the clinical problems associated with sarcoidosis might be related to a decreased anti-oxidant defence and we therefore measured the activity of the NADPH-generating enzyme glucose-6-phosphate dehydrogenase (G6PD), the GSH-regenerating enzyme glutathione reductase (GR) and indirectly the level of NADPH in red blood cells from patients with sarcoidosis. METHODS: In a population of sarcoidosis (n = 88) patients, G6PD, GR and GR activity after incubation with chromate (GR-Cr) were measured in erythrocytes. A decreased concentration of NADPH was revealed by an increased GR-Cr (> 0.6 IU/g Hb). To exclude a mutation in the G6PD gene, sequencing was performed in cases with an abnormal GR-Cr. Sarcoidosis pulmonary disease severity was evaluated by means of laboratory data, radiographic staging, HRCT scoring, pulmonary function and exercise capacity testing. RESULTS: Fourteen (29.2%) females and one (2.5%) male demonstrated an increased GR-Cr test, indicative of a decreased NADPH level. Patients with an abnormal test result demonstrated also significantly increased ACE and GR values (p < 0.05). Only one female case (of 6 tested) appeared to have a mutation in the G6PD gene. CONCLUSION: In a considerable percentage of female patients with sarcoidosis, a decreased level of NADPH in the erythrocytes was found.

Adolescent↗
PubMedDate not supplied

Biomarkers.

Explore the source record for details and available documents.

Amino Acids↗
PubMedDate not supplied

The effect of the trolox equivalent antioxidant capacity (TEAC) in plasma on the formation of 4-aminobiphenylhaemoglobin adducts in smokers.

Smokers are exposed to a number of carcinogenic compounds including aromatic amines such as 4-aminobiphenyl. Antioxidants are thought to be involved in the defence against the damaging effect of such carcinogens. Recently it has been shown that plasma antioxidant status in smokers is diminished compared with non-smokers. In this study we investigated in 40 smokers whether the trolox equivalent antioxidant capacity (TEAC) in plasma could be quantitatively related to exposure to cigarette smoke. The biomarkers 4-aminobiphenylhaemoglobin (4-ABP-Hb) adduct and cotinine were determined as indices of cigarette smoke exposure. A correlation between 4-ABP-Hb adduct levels and plasma cotinine levels was found for the whole population studied, who smoked 4-70 cigarettes per day (n = 40, r(2) = 0.12, p = 0.03). A significant inverse relationship was found between TEAC and 4-ABP-Hb levels (n = 40, r(2) = 0.17, p = 0.008). Multiple regression analysis showed a strong relationship between 4-ABP-Hb levels and plasma TEAC and cotinine levels (n = 40, r(2) =0.29, p = 0.002). These findings provide strong evidence that the 4- ABP-Hb adduct represents a valuable biomarker of (internal) exposure to tobacco smoke, and also that the formation of this marker is dependent on the plasma antioxidant status. The multiple regression analysis results show that the measure of effect (4-ABP-Hb adduct formation) is largely determined by dose (cotinine) and protection (TEAC).

Adult↗
PubMedDate not supplied

Effect of vitamin E on glutathione-dependent enzymes.

Reactive oxygen species and various electrophiles are involved in the etiology of diseases varying from cancer to cardiovascular and pulmonary disorders. The human body is protected against damaging effects of these compounds by a wide variety of systems. An important line of defense is formed by antioxidants. Vitamin E (consisting of various forms of tocopherols and tocotrienols) is an important fat-soluble, chain-breaking antioxidant. Besides working as an antioxidant, this compound possesses other functions with possible physiological relevance. The glutathione-dependent enzymes form another line of defense. Two important enzymes in this class are the free radical reductase and glutathione S-transferases (GSTs). The GSTs are a family of phase II detoxification enzymes. They can catalyze glutathione conjugation with various electrophiles. In most cases the electrophiles are detoxified by this conjugation, but in some cases the electrophiles are activated. Antioxidants do not act in isolation but form an intricate network. It is, for instance, known that vitamin E, together with glutathione (GSH) and a membrane-bound heat labile GSH-dependent factor, presumably an enzyme, can prevent damaging effects of reactive oxygen species on polyunsaturated fatty acids in biomembranes (lipid peroxidation). This manuscript reviews the interaction between the two defense systems, vitamin E and glutathione-dependent enzymes. On the simplest level, antioxidants such as vitamin E have protective effects on glutathione-dependent enzymes; however, we will see that reality is somewhat more complicated.

Animals↗
PubMedDate not supplied

Efficacy of HOCl scavenging by sulfur-containing compounds: antioxidant activity of glutathione disulfide?

Hypochlorous acid (HOCl) is a bactericidal compound formed by activated neutrophils during inflammation. Overproduction of HOCl causes damage to tissues at the site of neutrophil accumulation. The deleterious effects of excessive HOCl formation can be attenuated using antioxidants. Thiols and thioethers are known to be very effective HOCl scavengers. In the present study, the potency of several sulfur-containing compounds to protect acetylcholinesterase, glutathione S-transferase P1-1 (GST P1-1) and alpha1-antiproteinease against inactivation by HOCl was determined. Surprisingly, glutathione disulfide was an effective protector of acetylcholinesterase against hypochlorous acid. Glutathione disulfide did not provide protection for GST P1-1 and alpha1-antiproteinease against oxidative inactivation by HOCl. The implications of this finding are discussed.

Acetylcholinesterase↗