Biomedical subjects

Guido R M M Haenen

Publications and source records attributed to Guido R M M Haenen.

At least 19 recordsLinked to original sources

PubMed2007

Alpha-tocopheryl phosphate is a novel apoptotic agent.

Alpha-tocopheryl succinate (TOS) is a well-known potent and selective apoptotic agent. This apoptotic activity has been ascribed to its detergent-like property which is also shared by the structurally related compound, alpha-tocopheryl phosphate (TOP). TOP meets the structural requirements that have been described for the apoptotic activity of TO esters, i.e. the combination of three structural, one functional, one signalling and one hydrophobic domain. In this study, we have investigated the effect of TOP on the osteosarcoma cell line MG-63 using TOS as a reference compound. As compared with TOS, TOP showed a higher proliferative and apoptosis inducing activity on the MG-63 cancer cell line. The cytotoxic effect of TOP and TOS seems to be due to the effect of the intact compounds, since only a minor conversion into alpha-tocopheryl (TO) could be detected. EPR experiments showed that TOS and TOP reduced membrane fluidity, whereas TO had no effect. In addition, induction of erythrocyte hemolysis by TOP depended on the pH. These results suggest that the detergent-like activity of these compounds might be involved in their biological effect. Due to the potent biological activities, TOP might be clinically useful.

Apoptosis↗

PubMed2007

Oxidative stress reduces the muscarinic receptor function in the urinary bladder.

AIMS: Several pathophysiological conditions in the urinary bladder, for example, ischemia/reperfusion and inflammation are characterized by the formation of reactive oxygen species (ROS). The ROS are highly toxic because they can destroy proteins, DNA, and lipids. The aim of this study was to investigate the effect of oxidative stress on excitation-contraction coupling of detrusor smooth muscle. MATERIALS AND METHODS: Smooth muscle strips were dissected from pig urinary bladder and mounted in organ baths. Oxidative stress was mimicked by the addition of Cumene hydroperoxide (CHP), a lipophilic hydroperoxide, to the organ baths. Contractile responses to electrical field stimulation (EFS: 4-32 Hz), carbachol (10(-8)-3 x 10(-5) M), potassium (65.3 mM), and ATP (1 mM) were monitored before and after the addition of CHP. RESULTS: Responses of detrusor strips to EFS were for the greater part based on neurogenic stimulation and the release of acetylcholine. CHP diminished contractile responses to EFS and carbachol to the same extent. The pD(2) value of the carbachol concentration-response curve decreased significantly after exposure to 0.1 mM, 0.4 mM, 0.8 mM CHP. Furthermore the maximal effect obtained with carbachol was significantly reduced after 0.1 mM, 0.4 mM, and 0.8 mM CHP treatment. Contractions induced by potassium and ATP were significantly less affected by oxidative stress compared to EFS- and carbachol-induced responses of comparable amplitude. CONCLUSIONS: The results of our study demonstrate that oxidative stress induced by CHP affects pig bladder contractility. The muscarinic receptor signaling system is severely damaged. L-type calcium channels and the contractile system are less affected and cholinergic nerves remain largely unaffected.

Anesthetics, Local↗

PubMed2006

Enteral feeding enriched with carotenoids normalizes the carotenoid status and reduces oxidative stress in long-term enterally fed patients.

BACKGROUND & AIMS: Circulating carotenoid levels decrease progressively in patients receiving long-term enteral tube feeding with carotenoid-free formulas. Low dietary intake and low blood levels of carotenoids are associated with a higher risk of morbidity and mortality from chronic diseases. The aim of this study was to examine the effects of a low dose carotenoid mixture (3-mg/1500kcal) for 3 months on serum carotenoid levels and oxidative stress in patients receiving long-term enteral nutrition as the sole source of nutrition. METHODS: This randomized, double blind, controlled study compared patients receiving enteral nutrition with carotenoids (N=26) and without carotenoids (control group; N=25). RESULTS: Patients on long-term enteral nutrition had low baseline serum carotenoid levels. Three months of enteral feeding enriched with carotenoids significantly (P<0.01) increased serum carotenoid levels compared with the control group. Oxidative stress as measured by NF-kappaB levels was decreased at 3 months compared with the control group (P<0.05). No significant changes in MDA levels were observed during the study period in either group. CONCLUSIONS: This study demonstrated that enteral nutrition containing small amounts of carotenoids (3-mg/1500kcal) in patients requiring long-term enteral feeding normalizes serum carotenoid levels to the lower end of the range found in age-matched controls. The NF-kappaB data indicate a reduction in oxidative stress in these patients. Therefore, the use of formulas containing a mixture of carotenoids should be recommended for long-term enteral nutrition.

Aged↗

PubMed2006

Gene expression in human small intestinal mucosa in vivo is mediated by iron-induced oxidative stress.

Iron-induced oxidative stress in the small intestine may alter gene expression in the intestinal mucosa. The present study aimed to determine which genes are mediated by an iron-induced oxidative challenge in the human small intestine. Eight healthy volunteers [22 yr(SD2)] were tested on two separate occasions in a randomized crossover design. After duodenal tissue sampling by gastroduodenoscopy, a perfusion catheter was inserted orogastrically to perfuse a 40-cm segment of the proximal small intestine with saline and, subsequently, with either 80 or 400 mg of iron as ferrous gluconate. After the intestinal perfusion, a second duodenal tissue sample was obtained. Thiobarbituric acid-reactive substances, an indicator of lipid peroxidation, in intestinal fluid samples increased significantly and dose dependently at 30 min after the start of perfusion with 80 or 400 mg of iron, respectively (P < 0.001). During the perfusion with 400 mg of iron, the increase in thiobarbituric acid-reactive substances was accompanied by a significant, momentary rise in trolox equivalent antioxidant capacity, an indicator of total antioxidant capacity (P < 0.05). The expression of 89 gene reporters was significantly altered by both iron interventions. Functional mapping showed that both iron dosages mediated six distinct processes. Three of those processes involved G-protein receptor coupled pathways. The other processes were associated with cell cycle, complement activation, and calcium channels. Iron administration in the small intestine induced dose-dependent lipid peroxidation and a momentary antioxidant response in the lumen, mediated the expression of at least 89 individual gene reporters, and affected at least six biological processes.

Adult↗

PubMed2006

Effects of lipoic acid and dihydrolipoic acid on 4-aminophenol-mediated erythrocytic toxicity in vitro.

The effects of the antioxidant lipoic acid and its reduced form, dihydrolipoic acid (DHLA), were studied on the process of the erythrocytic toxicity of 4-aminophenol in human erythrocytes in vitro. 4-Aminophenol alone caused a stepwise increase in methaemoglobin formation, along with a commensurate decrease in total thiols. At 10 min., in the presence of lipoic acid alone and the thiol depletor 1-chloro-2,4-dinitrobenzene (CDNB) alone, 4-aminophenol-mediated methaemoglobin formation was significantly increased, whilst thiol levels were significantly reduced compared with the 4-aminophenol alone. At 10 min., with DHLA and CDNB alone, 4-aminophenol was associated with significantly increased methaemoglobin formation. However, thiol levels were not significantly different in the presence of DHLA compared with 4-aminophenol alone, although thiol levels were different compared with control (4-aminophenol alone) in the incubations with CDNB alone. At 15 min., only CDNB/4-aminophenol methaemoglobin formation differed from control, whilst thiol levels were significantly lower in the presence of CDNB alone compared with 4-aminophenol alone. Lipoic acid enhanced the toxicity of 4-aminophenol in terms of increased methaemoglobin formation coupled with increased thiol depletion, whilst DHLA showed increased 4-aminophenol-mediated methaemoglobin formation without thiol depletion. Lipoic acid, and to a lesser extent its reduced derivative DHLA, acted as a prooxidant in the presence of 4-aminophenol, enhancing the oxidative stress effects of the amine in human erythrocytes.

Adult↗

PubMed2005

The reversibility of the glutathionyl-quercetin adduct spreads oxidized quercetin-induced toxicity.

Quercetin is one of the most prominent dietary antioxidants. During its antioxidant activity, quercetin becomes oxidized into its o-quinone/quinone methide QQ. QQ is toxic since it instantaneously reacts with thiols of, e.g., proteins. In cells, QQ will initially form an adduct with glutathione (GSH), giving GSQ. We have found that GSQ is not stable; it dissociates continuously into GSH and QQ with a half life of 2min. Surprisingly, GSQ incubated with 2-mercapto-ethanol (MSH), a far less reactive thiol, results in the conversion of GSQ into the MSH-adduct MSQ. A similar conversion of GSQ into relatively stable protein thiol-quercetin adducts is expected. With the dithiol dihydrolipoic acid (L(SH)(2)), quercetin is formed out of GSQ. These results indicate that GSQ acts as transport and storage of QQ. In that way, the initially highly focussed toxicity of QQ is dispersed by the formation of GSQ that finally spreads QQ-induced toxicity, probably even over cells.

Glutathione↗

PubMed2005

No role of DT-diaphorase (NQO1) in the protection against oxidized quercetin.

Quercetin is one of the most studied alimentary antioxidants. During its antioxidant activity, quercetin becomes oxidized into its ortho-quinone/quinone methide, denoted as QQ. QQ is toxic since it is highly reactive towards thiols. DT-diaphorase (NQO1) might protect against QQ toxicity by reducing QQ to quercetin. However, conflicting data have been reported. The aim of the present study is to elucidate the role of DT-diaphorase in the protection against QQ-mediated thiol reactivity. It was found that QQ is indeed a substrate for DT-diaphorase. However, QQ reacted much faster with glutathione or protein thiols than with DT-diaphorase in experiments with isolated compounds as well as with human liver cytosol or blood plasma. This indicates that DT-diaphorase has no role in the protection against QQ.

Chromatography, High Pressure Liquid↗

PubMed2005

Altered antioxidant status in peripheral skeletal muscle of patients with COPD.

Despite the growing field of interest in the role of pulmonary oxidative stress in chronic obstructive pulmonary disease (COPD), barely any data are available with respect to antioxidant capacity in the peripheral musculature of these patients. The main objective of this study was to assess in detail the antioxidant status in skeletal muscle of patients with COPD. Biopsies from the vastus lateralis of 21 patients with COPD and 12 healthy age-matched controls were analysed. Total antioxidant capacity, vitamin E, glutathione, and uric acid levels were determined and the enzyme activities of superoxide dismutase, glutathione reductase, glutathione peroxidase, and glutathione-S-transferase were measured. Malondialdehyde was measured as an index of lipid peroxidation. The total antioxidant capacity and the uric acid levels were markedly higher in COPD patients than in healthy controls (25%, P = 0.006 and 24%, P = 0.029, respectively). Glutathione-S-transferase activity was also increased (35%; P = 0.044) in patients compared to healthy subjects. Vitamin E level was lower in patients than in controls (P < 0.05). The malondialdehyde level was not different between the two groups. It can be concluded that the muscle total antioxidant capacity is increased in patients with COPD. Together with the reduced vitamin E levels, the increased glutathione-S-transferase activity and normal levels of lipid peroxidation products, these findings suggest that the antioxidant system may be exposed to and subsequently triggered by elevated levels of reactive oxygen species.

Aged↗

PubMed2005

Determination of the antioxidant capacity in blood.

BACKGROUND: A vast amount of scientific research is directed towards the beneficial effects of antioxidants on health. For this reason, several assays have been developed to determine the total antioxidant capacity of blood. METHODS: In this study two procedures based on the use of the green-blue 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical (ABTS(*+)) were compared. In the first (commercially available) procedure, ABTS(*+) was generated in the presence of the blood sample. In the second procedure, referred to as the decolorization assay, antioxidants react with preformed ABTS(*+). RESULTS: It was found that the first procedure leads to greater underestimation of the actual antioxidant capacity and is more prone to artifacts than the second procedure. Therefore, only the latter procedure was evaluated in detail and it appeared that (i) plasma is preferred over serum, (ii) the high background produced by albumin can be circumvented by deproteination, (iii) samples can be stored at -80 degrees C for 12 months, and (iv) the assay has high precision. Due to poor linearity, the procedure has to be standardized to allow sample comparison. CONCLUSIONS: The decolorization assay is a reliable and robust assay that can be applied routinely to predict the antioxidant capacity of blood.

Antioxidants↗

PubMed2004

The extraordinary antioxidant activity of vitamin E phosphate.

The antioxidant activities of RRR-vitamin E (VE), all-rac-vitamin E (all-rac-VE), trolox, RRR-vitamin E acetate (VEA), all-rac-vitamin E phosphate (VEP) and RRR-vitamin E succinate (VES) were compared. In this study, the rank order in the inhibition of lipid peroxidation (LPO) of VE and its derivatives was trolox>VE approximately all-rac-VE>VEA>VES. VE and trolox inhibited LPO in non-heated and heated rat liver microsomes. It has generally been accepted that this is due to scavenging of free radicals by these antioxidants, and during this protection the antioxidants are oxidized. VEA and VES have to be converted into VE by esterases to obtain antioxidant activity against LPO. VEP, however, had a potent antioxidant effect of its own without conversion to VE. In contrast to VE, VEP is not consumed during this protection. Of the compounds tested, VEP is the most potent in induction of hemolysis of erythrocytes. EPR experiments using the spin label 16-doxylstearic acid showed that VEP reduces membrane fluidity, in contrast to VE. This indicates that VEP acts as a detergent and forms a barrier that might inhibit the transfer of radicals from one polyunsaturated fatty acid to another. This new mechanism may form the basis for a new class of antioxidants.

Animals↗

PubMed2004

Lecithinized copper,zinc-superoxide dismutase as a protector against doxorubicin-induced cardiotoxicity in mice.

Production of superoxide radicals from doxorubicin is widely accepted to be the cause of the cardiotoxicity induced by this antitumor agent. Pretreatment with superoxide dismutase could improve the therapeutic application. Aim of the present study was to determine whether lecithinized superoxide dismutase (PC-SOD) can serve as a cardioprotective drug during doxorubicin treatment. The protective potential of PC-SOD on doxorubicin-induced cardiotoxicity was investigated in BALB/c mice. The possible influence of PC-SOD on the antitumor activity of doxorubicin was investigated in vitro as well as in vivo. Mice were treated intravenously with doxorubicin (4 mg x kg(-1)) or doxorubicin and PC-SOD (5000, 20000 or 80000 U x kg(-1)) weekly x 6 and appropriate controls were included. Cardiotoxicity was monitored for 8 weeks by ECG measurement. The influence of PC-SOD on the antitumor activity of doxorubicin was evaluated in three human malignant cell lines. Nude mice bearing OVCAR-3 human ovarian cancer xenografts were treated intravenously with doxorubicin (8 mg x kg(-1)) alone or preceded by PC-SOD 20000 or 80000 U x kg(-1) weekly x 2 and appropriate controls were included. PC-SOD prevented doxorubicin-induced cardiotoxicity already at 5000 U x kg(-1) whereas 20000 and 80000 U x kg(-1) were equally protective. No toxicity was observed in mice treated with PC-SOD. PC-SOD did not interfere with the antiproliferative effects of doxorubicin in vitro. In vivo, PC-SOD had no negative effect on the inhibition of xenograft growth induced by doxorubicin. It can be concluded that PC-SOD protects the heart, but not the tumor against doxorubicin. These data suggest that PC-SOD may be a suitable cardioprotector during doxorubicin treatment.

Animals↗

PubMed2004

Antioxidant capacity of reaction products limits the applicability of the Trolox Equivalent Antioxidant Capacity (TEAC) assay.

The Trolox Equivalent Antioxidant Capacity (TEAC) assay is based on the scavenging of the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical (ABTS(*)) converting it into a colorless product. The degree of decolorization induced by a compound is related to that induced by trolox, giving the TEAC value. The assay is frequently used for constructing structure activity relationships (SARs). HPLC analysis of the reaction mixture, obtained after scavenging of ABTS(*) by the flavonoid chrysin, shows that a product is formed that also reacts with ABTS(*). The product has a higher antioxidant capacity and reacts faster with ABTS(*) than the parent compound, chrysin. In contrast to the reaction product of chrysin, the reaction product of trolox, which is formed during scavenging of ABTS(*), i.e. trolox quinone, does not react with ABTS(*). The experiments show that the TEAC is the antioxidant capacity of the parent compound plus the potential antioxidant capacity of the reaction product(s). This means that the TEAC assay does not necessarily reflect the antioxidant effect of only one structure. This hampers the applicability of the assay for the construction of SARs and for ranking antioxidants.

Antioxidants↗

PubMed2003

Lipoic acid protects efficiently only against a specific form of peroxynitrite-induced damage.

The ability of the sulfur-containing compounds glutathione (GSH), glutathione disulphide (GSSG), S-methylglutathione (GSMe), lipoic acid (LA), and dihydrolipoic acid (DHLA) to protect against hypochlorous acid (HOCl)-mediated damage and peroxynitrite (ONOOH)-induced damage has been compared. Protective activity was assessed in competition assays by monitoring several detectors, i.e. dihydrorhodamine-123 (DHR-123) oxidation, alpha(1)-antiproteinase (alpha(1)-AP) inactivation, and glutathione S-transferase P1-1 (GST-P1-1) inactivation. In addition, nitration of tyrosine was measured to assess protection of the sulfur-containing compounds against ONOOH. For protection against HOCl, the efficacy of the antioxidant was controlled by the ratio of the reaction rates of the antioxidant and the detector molecule with the oxidant. The rank order of the activity of the antioxidants (GSH > DHLA approximately LA approximately GSMe > GSSG) appeared to be independent of the detector used. However, the rank order of the antioxidants against ONOOH-induced damage is strongly dependent on the detector. LA was 40 times less active than GSH in the inhibition of ONOOH-induced DHR-123 oxidation, whereas LA was 20 times more active than GSH in preventing the inhibition of GST-P1-1 by ONOOH. This points to different molecular mechanisms of ONOOH damage to DHR-123 compared with ONOOH damage to GST-P1-1. LA is a poor antioxidant in protecting against the form of ONOOH damage involved in DHR-123 oxidation. In the form of ONOOH toxicity involved in GST-P1-1 inhibition, LA is the most potent sulfur-containing antioxidant in our series. It is proposed that an intermediate product in which both sulfur atoms of LA have reacted is involved in the reaction of ONOOH with LA. The high potency of LA to protect GST-P1-1 against ONOOH might be of therapeutic interest.

Antioxidants↗

PubMed2003

Tetrahydrofolate and 5-methyltetrahydrofolate are folates with high antioxidant activity. Identification of the antioxidant pharmacophore.

The presumed protective effect of folic acid on the pathogenesis of cardiovascular, hematological and neurological diseases and cancer has been associated with the antioxidant activity of folic acid. Peroxynitrite (PON) scavenging activity and inhibition of lipid peroxidation (LPO) of the physiological forms of folate and of structurally related compounds were tested. It was found that the fully reduced forms of folate, i.e. tetrahydrofolate (THF) and 5-methyltetrahydrofolate (5-MTHF), had the most prominent antioxidant activity. It appeared that their protection against LPO is less pronounced than their PON scavenging activity. The antioxidant activity of these forms of folic acid resides in the pterin core, the antioxidant pharmacophore is 4-hydroxy-2,5,6-triaminopyrimidine. It is suggested that an electron donating effect of the 5-amino group is of major importance for the antioxidant activity of 4-hydroxy-2,5,6-triaminopyrimidine. A similar electron donating effect is probably important for the antioxidant activity of THF and 5-MTHF.

Animals↗

PubMed2003

Oxidized quercetin reacts with thiols rather than with ascorbate: implication for quercetin supplementation.

When an antioxidant scavenges a reactive species, i.e., when it exerts its antioxidant activity, the antioxidant is converted into potentially harmful oxidation products. In this way, the antioxidant quercetin might yield an ortho-quinone, denoted as QQ, which has four tautomeric forms, i.e., the ortho-quinone and three quinonmethides. We evaluated the interaction of QQ with ascorbate or glutathione (GSH). Ascorbate recycles QQ to the parent compound quercetin, while GSH forms two adducts with QQ, i.e., 6-GSQ and 8-GSQ. When both GSH and ascorbate are present, QQ is converted exclusively into GSQ. In the absence of GSH, protein thiols will be arylated by QQ. This protein arylation is not prevented by ascorbate. Thiol arylation by quinones and quinonmethides can impair several vital enzymes. This implies that the product formed when quercetin displays its antioxidant scavenging effect is toxic in the absence of GSH. Therefore, an adequate GSH level should be maintained when quercetin is supplemented.

Antioxidants↗

PubMed2003

Bioavailability and pharmacokinetics of the cardioprotecting flavonoid 7-monohydroxyethylrutoside in mice.

PURPOSE: The pharmacokinetics and bioavailability of monoHER, a promising protector against doxorubicin-induced cardiotoxicity, were determined after different routes of administration. METHODS: Mice were treated with 500 mg.kg(-1) monoHER intraperitoneally (i.p.), subcutaneously (s.c.) or intravenously (i.v.) or with 1000 mg.kg(-1) orally. Heart tissue and plasma were collected 24 h after administration. In addition liver and kidney tissues were collected after s.c. administration. The levels of monoHER were measured by HPLC with electrochemical detection. RESULTS: After i.v. administration the AUC(0-120 min) values of monoHER in plasma and heart tissue were 20.5+/-5.3 micromol.min.ml(-1) and 4.9+/-1.3 micromol.min.g(-1) wet tissue, respectively. After i.p. administration, a mean peak plasma concentration of about 130 microM monoHER was maintained from 5 to 15 min after administration. The AUC(0-120 min) values of monoHER were 6.1+/-1.1 micromol.min.ml(-1) and 1.6+/-0.4 micromol.min.g(-1) wet tissue in plasma and heart tissue, respectively. After s.c. administration, monoHER levels in plasma reached a maximum (about 230 microM) between 10 and 20 min after administration. The AUC(0-120 min) values of monoHER in plasma, heart, liver and kidney tissues were 8.0+/-0.6 micromol.min.ml(-1), 2.0+/-0.1, 22.4+/-2.0 and 20.5+/-5.7 micromol.min.g(-1), respectively. The i.p. and s.c. bioavailabilities were about 30% and 40%, respectively. After oral administration, monoHER could not be detected in plasma, indicating that monoHER had a very poor oral bioavailability. CONCLUSIONS: MonoHER was amply taken up by the drug elimination organs liver and kidney and less by the target organ heart. Under cardioprotective conditions (500 mg/kg, i.p.), the Cmax was 131 microM and the AUC(infinity) was 6.3 microM.min. These values will be considered endpoints for the clinical phase I study of monoHER.

Administration, Oral↗

PubMed2003

Systemic poly(ADP-ribose) polymerase-1 activation, chronic inflammation, and oxidative stress in COPD patients.

Oxidative stress and systemic inflammation in chronic obstructive pulmonary disease (COPD) strongly suggest a role for the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1, E.C.2.4.2.30) in the disease pathophysiology. PARP-1 is highly activated by reactive oxygen species-induced DNA strand breaks, upon which it forms extensive poly(ADP-ribose) (PAR) polymers from its substrate NAD(+). We hypothesized that in COPD, chronic inflammation and oxidative stress would lead to systemic PARP-1 activation and to a reduced NAD(+) status. In a patient-control study, systemic PARP-1 activation was assessed by immunofluorescent detection of PAR polymers in peripheral blood lymphocytes. The percentage of PAR polymer-positive lymphocytes appeared to be higher in COPD patients (27 +/- 3%) than in healthy age-matched controls (17 +/- 2%, p <.05). Trolox equivalent antioxidant capacity (TEAC) of deproteinized plasma (p <.001), plasma uric acid (p <.05), as well as blood NAD(+) (p <.01) of stable COPD patients were significantly reduced when compared to controls. In addition, levels of proinflammatory cytokines IL-6, IL-8, and sICAM-1 were increased (p <.005) in COPD patients. In this study, evidence was found for the presence of systemic inflammation, chronic oxidative stress, and systemic PARP-1 activation in stable COPD patients. These data support a contribution of oxidative stress-induced PARP-1 activation to the pathophysiology of COPD.

Antioxidants↗

PubMed2003

New method to study oxidative damage and antioxidants in the human small bowel: effects of iron application.

Iron may induce oxidative damage to the intestinal mucosa by its catalyzing role in the formation of highly reactive hydroxyl radicals. This study aimed to determine iron-induced oxidative damage provoked by a single clinical dosage of ferrous sulfate and to elucidate the antioxidant defense mechanisms in the human small intestine in vivo. A double-lumen perfusion tube was positioned orogastrically into a 40-cm segment of the proximal small intestine in six healthy volunteers (25 +/- 5 yr). The segment was perfused with saline and subsequently with saline containing 80 mg iron as ferrous sulfate at a rate of 10 ml/min. Intestinal fluid samples were collected at 15-min intervals. Thiobarbituric acid reactive substances concentrations as an indicator of lipid peroxidation increased significantly from 0.07 microM (range, 0-0.33 microM) during saline perfusion to 3.35 microM (range, 1.19-7.27 microM) during iron perfusion (P < 0.05). Nonprotein antioxidant capacity increased significantly from 474 microM (range, 162-748 microM) to 1,314 microM (range, 674-1,542 microM) (P < 0.05). These data show that a single dosage of ferrous sulfate induces oxidative damage and the subsequent release of an antioxidant in the small intestine in vivo in healthy volunteers.

Adult↗