Increased Xanthine Oxidase Research Articles

Endotoxin challenge increases xanthine oxidase activity in cattle: effect of growth hormone and vitamin E treatment

In addition to its basic role in the metabolism of purine nucleotides, xanthine oxidoreductase (XOR) is involved in the generation of oxygen-derived free radicals and production and metabolic fate of nitric oxide (NO). Growth hormone (GH) and Vitamin E (E) have been shown previously to modify immune response to infection. Our objective was to determine in heifers the effect of endotoxin challenge (LPS; 3.0 μg/kg BW, i.v. bolus, Escherichia coli 055:B5) on xanthine oxidase (XO) activity in plasma and liver and the modification of this response by daily treatment with recombinant GH (0.1 mg/kg BW, i.m., for 12 days) or GH+E (E: mixed tocopherol, 1000 IU/heifer, i.m., for 5 days). In experiment 1, 16 heifers (348.7±6.1 kg) were assigned to control (C, daily placebo injections), GH, or GH+E treatments and were challenged with two consecutive LPS injections (LPS1 and LPS2, 48 h apart). After LPS1, plasma XO activity increased 290% ( P<0.001) at 3 h, reached peak (430%) at 24 h and returned to basal level by 48 h after LPS2. XO responses (area under the time×activity curve, AUC) were greater after LPS1 than LPS2 ( P<0.001). Total plasma XO responses to LPS (AUC, LPS1+LPS2) were augmented 55% ( P<0.05) over C with GH treatment but diminished to C responses in GH+E. There was a linear relationship ( r 2=0.605, P<0.001) between total response in plasma XO activity and plasma nitrate+nitrite concentration. In experiment 2, 24 heifers (346±6 kg) were assigned to C or GH treatments and liver biopsy samples were obtained at 0, 3, 6, and 24 h after a single LPS challenge. Hepatic XO activities increased 63.3% ( P<0.05) 6 h after single LPS challenge and remained elevated at 24 h (100.1%, P<0.01) but were not affected by GH treatment. Results indicate that LPS-induced increases in plasma XO activity could be amplified by previous GH treatment but attenuated by E administration. The data also suggest that E may be effective in controlling some mediators of immune response associated with increased production of NO via the effect on XO activity and its production of superoxide anion as well as uric acid.

Sources of oxygen radicals in brain in acute ammonia intoxication in vivo

The effects of acute ammonia intoxication on reactive oxygen species production by different sources in rat brain were studied. Ammonia intoxication in vivo leads to reduced activity of superoxide dismutase (SOD), catalase and glutathione peroxidase in brain nonsynaptic mitochondria and increased formation of O 2 − by submitochondrial particles. It also results in increased xanthine oxidase (XO) activity and decreased xanthine dehydrogenase (XDH)/XO activity ratio indicating conversion of XDH to XO and also increases monoamine oxidase A (MAO-A) activity but not of MAO-B. Blocking NMDA receptors with MK-801 prevents ammonia-induced oxidative stress, XDH to XO conversion and MAO-A activation. Ammonia intoxication did not lead to H 2O 2 formation by mitochondria, in spite of increased O 2 − generation. The main source of H 2O 2 in the mitochondrial matrix was Mn-SOD. Ammonia intoxication in vivo leads to increased superoxide and decreased hydrogen peroxide in nonsynaptic brain mitochondria. Increased superoxide is due to increased formation by the respiratory chain and by xanthine and aldehyde oxidases and decreased elimination by antioxidant enzymes. The reduced formation of hydrogen peroxide is due to the reduced activity of Mn-SOD. Prevention of ammonia-induced production of reactive oxygen species by MK-801 supports the idea that it is mediated by activation of NMDA receptors.

Electron spin resonance characterization of vascular xanthine and NAD(P)H oxidase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation.

Increased inactivation of nitric oxide by superoxide (O2*-) contributes to endothelial dysfunction in patients with coronary disease (CAD). We therefore characterized the vascular activities of xanthine oxidase and NAD(P)H oxidase, 2 major O2*--producing enzyme systems, and their relationship with flow-dependent, endothelium-mediated vasodilation (FDD) in patients with CAD. Xanthine- and NAD(P)H-mediated O*.- formation was determined in coronary arteries from 10 patients with CAD and 10 controls by using electron spin resonance spectroscopy. Furthermore, activity of endothelium-bound xanthine oxidase in vivo and FDD of the radial artery were determined in 21 patients with CAD and 10 controls. FDD was measured before and after infusion of the antioxidant vitamin C (25 mg/min i.a.) to determine the portion of FDD inhibited by radicals. In coronary arteries from patients with CAD, xanthine- and NAD(P)H-mediated O2*- formation was increased compared with controls (xanthine: 12+/-2 versus 7+/-1 nmol O2*-/ microg protein; NADH: 11+/-1 versus 7+/-1 nmol O2*-/ microg protein; and NADPH: 12+/-2 versus 9+/-1 nmol O2*-/ microg protein; each P<0.05). Endothelium-bound xanthine oxidase activity was increased by >200% in patients with CAD (25+/-4 versus 9+/-1 nmol O2*-/ microL plasma per min; P<0.05) and correlated inversely with FDD (r=-0.55; P<0.05) and positively with the effect of vitamin C on FDD (r=0.54; P<0.05). The present study represents the first electron spin resonance measurements of xanthine and NAD(P)H oxidase activity in human coronary arteries and supports the concept that increased activities of both enzymes contribute to increased vascular oxidant stress in patients with CAD. Furthermore, the present study suggests that increased xanthine oxidase activity contributes to endothelial dysfunction in patients with CAD and may thereby promote the atherosclerotic process.

Heat preconditioning prevents oxidative stress-induced damage in the intestine and lung following surgical manipulation.

The intestine is increasingly recognized as a primary effector of distant organ damage, such as lung, following abdominal surgery. Surgical manipulation of the intestine generates oxygen free radicals resulting in mucosal damage. Heat preconditioning has been proposed to prevent various stress-induced alterations in cells and tissues, including oxidative stress. This study examined the effect of heat preconditioning on oxidative stress-induced damage to the intestine and lung, following surgical manipulation. Control rats and rats pretreated with heat were subjected to surgical manipulation by opening the abdominal wall and handling the intestine as done during laparotomy. Intestine and lung were assessed for damage by histology and markers of oxidative stress. Surgical manipulation resulted in ultrastructural changes in the intestine. Biochemical alterations in the enterocytes were evident, with increased xanthine oxidase activity resulting in production of superoxide anion and with a decrease in antioxidant status. Gut manipulation also resulted in neutrophil infiltration and oxidative stress in the lung as assessed by histology, myeloperoxidase activity, lipid peroxidation and antioxidant status. Heat conditioning before surgical manipulation had a protective effect against this intestinal and lung damage. This study suggests that mild whole-body hyperthermia before surgery might offer protection from postoperative complications.

The activities of serum adenosine deaminase and xanthine oxidase enzymes in Behcet's disease

Background: Adenosine deaminase (AD) and xanthine oxidase (XO) are enzymes of purine catabolism that catalyze the conversion of adenosine to inosine, deoxyadenosine to deoxyinosine, hypoxanthine to xanthine and xanthine to uric acid, respectively. AD is known to be an important enzyme in the maturation and function of T lymphocytes. The aim of this prospective study was to evaluate whether there are changes in serum AD activity as an index of T lymphocyte function in Behcet's disease (BD) which is known as having T cell-mediated immune response. Methods: A total of 32 patients and 26 sex- and age-matched healthy control subjects were analysed for AD and XO activities. The patients with BD were divided into two subgroups: BD with and without eye lesions. Twelve patients with complete BD and four patients with incomplete BD had eye complications. AD and XO activities in serum were measured with spectrophotometric methods. Results: There was a remarkable increase in AD activity and moderate increase in XO in patients with BD compared to controls indicating T cell activation and increased maturation. Serum AD activity of complete BD was higher than that of incomplete BD. There was no difference in XO activity between the subgroups of BD. Significant positive correlation was found between AD and XO in BD, although there was no correlation in control group. Conclusions: The results indicate that increased AD and XO activities may provide an additional benefit for the diagnosis of BD and subtyping of the disease as having eye complication or not and complete and incomplete BD. Further studies are needed to bring to light the exact mechanism of AD and XO activity elevation.

Intestinal mucosal alterations in experimental cirrhosis in the rat: Role of oxygen free radicals

Cirrhosis is associated with altered gastrointestinal function, and bacterial translocation from the gut plays an important role in the etiology of spontaneous bacterial peritonitis (SBP) seen in this condition. Although alterations in gut motility and intestinal permeability are recognized in cirrhosis, the intestinal damage at the cellular and subcellular levels is not well understood. This study looked at the mucosal alterations in experimental cirrhosis and the role of oxygen free radicals in this process. It was shown that cirrhosis results in oxidative stress in the intestine, as seen by increased xanthine oxidase (XO) activity and altered antioxidant status. Cirrhosis also affects enterocyte mitochondrial function, as assessed by respiratory control ratio, swelling, and calcium flux. Increased lipid peroxidation of the brush border membranes (BBMs) was seen along with altered intestinal transport. In conclusion, this study shows that intestinal mucosal alterations are seen in experimental cirrhosis and are possibly mediated by oxidative stress. (HEPATOLOGY 2002;35:622-629.)

Nitric Oxide Protects the Intestine from the Damage Induced by Laparotomy and Gut Manipulation

Background. The intestine is highly susceptible to free radical–induced damage, and our earlier work has shown that surgical stress induces the generation of oxygen free radicals in enterocytes, resulting in intestinal damage along with ultrastructural changes. Since nitric oxide (NO) is an important mediator of gastrointestinal function, this study looked at the effect of NO on surgical stress–induced intestinal alterations.Materials and methods. Control rats and rats pretreated with the NO donor l-arginine were subjected to surgical stress by opening the abdominal wall and handling the intestine as done during laparotomy. Enterocytes were isolated and homogenate prepared, and the protection offered by l-arginine against damage due to surgical stress was determined and compared with normal controls. Protection to structural as well as functional aspects of the intestine was also examined.Results. Intestinal manipulation affected intestinal structure as assessed by electron microscopy. Functional impairment of the enterocyte was also evident, with increased xanthine oxidase activity resulting in production of superoxide anion. This impairment is more dramatic in the crypt cells. Increased protease activity was also seen following laparotomy and handling. Pretreatment with the NO synthase substrate l-arginine prevented these damaging effects. Arginine protection was abolished in the presence of the NO synthase inhibitor NG-nitro-l-arginine methyl ester, indicating the role of NO.Conclusion. Stress in the small intestine due to any surgery can affect enterocyte structure and function. These damaging effects can be prevented by NO, an important modulator of cellular function.

Aluminium increases xanthine oxidase activity and disturbs antioxidant status in the rat

The mechanisms responsible for the neurotoxic effects of Al remain poorly understood. In order to determine whether Al promotes oxidative stress in vivo, we measured the enzymatic activity of xanthine oxidase (XO), superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione-S-transferase (GST) and glutathione reductase (GR) in four groups of rats after eight days of intraperitoneal administration of variable concentrations of Al (0, 5, 10, and 15 mg/kg body weight, respectively). XO activity was measured in both plasma and liver samples, and the activities of the remaining enzymes were further determined in the brain and red blood cells (RBC). The most significant changes were observed in XO and GPX activities, that were enhanced and depressed, respectively. In both instances, the enzyme activities were correlated with Al concentrations, either positively (XO) or negatively (GPX). Enhancement of XO and inhibition of GPX activity may lead to the accumulation of intermediate toxic compounds such as hydrogen peroxide and hydroxyl radicals, since SOD activity is increased as well. The latter finding must be taken with some caution because previous studies have shown contradictory results in this field. Our data suggest that Al toxicity could be mediated by its action on both pro- and anti-oxidant enzymes. The biological significance of these findings remains to be established.

Effect of Nitric Oxide Synthase Inhibitors on Lipid Peroxide Formation in Liver Caused by Endotoxin Challenge

Abstract:This study investigated the effect of nitric oxide on lipid peroxide formation during endotoxaemia. Nitric oxide synthase inhibitors NG‐monomethyl‐L‐arginine acetate (L‐NMMA, 20 mg/kg, intravenously), NG‐nitro‐L‐arginine‐methyl ester (L‐NAME, 10 mg/kg, intravenously), and NG‐nitro‐L‐arginine (L‐NA, 10 mg/kg, intravenously), and a relatively selective inducible nitric oxide synthase inhibitor aminoguanidine (10 mg/kg, intravenously), did not protect against endotoxin‐induced death of mice. Superoxide dismutase activity in liver 18 hr after administration of endotoxin (6 mg/kg, intraperitoneally) to L‐arginine analogues (L‐NMMA, L‐NAME, L‐NA)‐treated mice was lower than in mice treated with endotoxin alone, whereas the administration of L‐arginine analogues increased xanthine oxidase activity in the livers of endotoxin‐injected mice compared with mice treated with endotoxin alone. In mice treated with L‐arginine analogues and aminoguanidine, the levels of non‐protein sulfhydryl and lipid peroxide in liver 18 hr after endotoxin injection did not show significant differences from mice treated with endotoxin alone. L‐Arginine analogues and aminoguanidine had little effect on lipid peroxide formation in liver caused by endotoxin. Treatment with aminoguanidine (300 μM) significantly inhibited endotoxin‐induced intracellular peroxide in J774A.1 cells, however, aminoguanidine did not affect endotoxin‐induced cytotoxicity in J774A.1 cells. Our results clearly demonstrate that treatment with catalase (10 μg/ml), D‐mannitol (10 mM), or superoxide dismutase (100 U/ml), has little or no effect on nitric oxide production by endotoxin (1 μg/ml)‐activated J774A.1 cells. These findings suggest that nitric oxide is not crucial for lipid peroxide formation during endotoxaemia. Therefore, it is unlikely that nitric oxide plays a significant role in liver injury caused by free radical generation in endotoxaemia.

Effect of nitric oxide synthase inhibitors on lipid peroxide formation in liver caused by endotoxin challenge.

This study investigated the effect of nitric oxide on lipid peroxide formation during endotoxaemia. Nitric oxide synthase inhibitors N(G)-monomethyl-L-arginine acetate (L-NMMA, 20 mg/kg, intravenously), N(G)-nitro-L-arginine-methyl ester (L-NAME, 10 mg/kg, intravenously), and N(G)-nitro-L-arginine (L-NA, 10 mg/kg, intravenously), and a relatively selective inducible nitric oxide synthase inhibitor aminoguanidine (10 mg/kg, intravenously), did not protect against endotoxin-induced death of mice. Superoxide dismutase activity in liver 18 hr after administration of endotoxin (6 mg/kg, intraperitoneally) to L-arginine analogues (L-NMMA, L-NAME, L-NA)-treated mice was lower than in mice treated with endotoxin alone, whereas the administration of L-arginine analogues increased xanthine oxidase activity in the livers of endotoxin-injected mice compared with mice treated with endotoxin alone. In mice treated with L-arginine analogues and aminoguanidine, the levels of non-protein sulfhydryl and lipid peroxide in liver 18 hr after endotoxin injection did not show significant differences from mice treated with endotoxin alone. L-Arginine analogues and aminoguanidine had little effect on lipid peroxide formation in liver caused by endotoxin. Treatment with aminoguanidine (300 microM) significantly inhibited endotoxin-induced intracellular peroxide in J774A.1 cells, however, aminoguanidine did not affect endotoxin-induced cytotoxicity in J774A.1 cells. Our results clearly demonstrate that treatment with catalase (10 microg/ml), D-mannitol (10 mM), or superoxide dismutase (100 U/ml), has little or no effect on nitric oxide production by endotoxin (1 microg/ml)-activated J774A.1 cells. These findings suggest that nitric oxide is not crucial for lipid peroxide formation during endotoxaemia. Therefore, it is unlikely that nitric oxide plays a significant role in liver injury caused by free radical generation in endotoxaemia.

A tungsten supplemented diet attenuates bacterial translocation in chronic portal hypertensive and cholestatic rats: role of xanthine dehydrogenase and xanthine oxidase

BACKGROUNDBacterial translocation (BT) plays a major role in the pathophysiological process of spontaneous infections in portal hypertension (PH) and cholestatic jaundice. The major mechanisms promoting BT in experimental animal models...

Surgical stress and the small intestine: Role of oxygen free radicals

Background: Any surgical procedure can be associated with altered intestinal function. The mechanism involved in these changes at the cellular level during surgical stress has not been worked out. This study looked at the biochemical and functional alterations, along with ultrastructural changes, in the intestine during surgical stress in a simple rat model. Methods: Surgical stress was induced by opening the abdominal wall and handling the intestine as during laparotomy. The effect of oxidative stress on the enterocyte and altered intestinal permeability as well as the ultrastructural changes to the mucosa were studied. Results: Surgical stress results in oxidative stress on enterocytes, as evidenced by increased xanthine oxidase and decreased catalase activity along with altered thiol redox status. This was associated with increased intestinal permeability and widened intercellular spaces. These changes were prominent at 60 minutes after laparotomy and returned to normal by 24 hours. Conclusions: Mild intestinal handling is capable of inducing oxidative stress in enterocytes; this could be one of the mechanisms by which intestinal mucosal alterations occur during surgical stress. (Surgery 1999;125:560-9.)

Surgical stress and the small intestine: Role of oxygen free radicals

Background: Any surgical procedure can be associated with altered intestinal function. The mechanism involved in these changes at the cellular level during surgical stress has not been worked out. This study looked at the biochemical and functional alterations, along with ultrastructural changes, in the intestine during surgical stress in a simple rat model. Methods: Surgical stress was induced by opening the abdominal wall and handling the intestine as during laparotomy. The effect of oxidative stress on the enterocyte and altered intestinal permeability as well as the ultrastructural changes to the mucosa were studied. Results: Surgical stress results in oxidative stress on enterocytes, as evidenced by increased xanthine oxidase and decreased catalase activity along with altered thiol redox status. This was associated with increased intestinal permeability and widened intercellular spaces. These changes were prominent at 60 minutes after laparotomy and returned to normal by 24 hours. Conclusions: Mild intestinal handling is capable of inducing oxidative stress in enterocytes; this could be one of the mechanisms by which intestinal mucosal alterations occur during surgical stress. (Surgery 1999;125:560-9.)

Are reactive oxygen species involved in the pathogenesis of murine cerebral malaria?

To investigate the involvement of oxidative tissue damage in the pathogenesis of murine cerebral malaria (CM), brain levels of protein carbonyls, 3,4-dihydroxyphenylalanine (DOPA), o-tyrosine, and dityrosine were measured during Plasmodium berghei ANKA (PbA) and P. berghei K173 (PbK) infections. During PbA infection in a CM model, brain levels of the substances were similar to those in uninfected mice. The role of phagocyte-derived reactive oxygen species in the pathogenesis of CM was examined in gp91phox gene knockout mice. The course of CM in these mice was the same as in their wild type counterparts. To examine whether superoxide production in the central nervous system could have occurred via increased xanthine oxidase activity, brain concentrations of urate were measured in CM mice and in mice infected with PbK (which does not cause CM). Brain urate concentration increased significantly in both groups of mice, suggesting that purine breakdown is not specific to CM. These results indicate that reactive oxygen species probably do not contribute to the pathogenesis of murine CM.

Uric acid in chronic heart failure: a marker of chronic inflammation.

Chronic heart failure is associated with hyperuricaemia and elevations in circulating markers of inflammation. Activation of xanthine oxidase, through free radical release, causes leukocyte and endothelial cell activation. Associations could therefore be expected between serum uric acid level, as a marker of increased xanthine oxidase activity, and markers of inflammation. We have explored these associations in patients with chronic heart failure, taking into account the hyperuricaemic effects of diuretic therapy and insulin resistance. Circulating uric acid and markers of inflammation were measured in 39 male patients with chronic heart failure and 16 healthy controls. All patients underwent a metabolic assessment, which provided a measure of insulin sensitivity (intravenous glucose tolerance tests and minimal modelling analysis). Compared to controls, patients with chronic heart failure had significantly higher levels of circulating uric acid, interleukin-6, soluble tumour necrosis factor receptor (sTNFR)-1, soluble intercellular adhesion molecule-1 (ICAM-1, all P<0.001), E-selectin and sTNFR2 (both P<0.05). In patients with chronic heart failure, serum uric acid concentrations correlated with circulating levels of sTNFR1 (r=0.74), interleukin-6 (r=0.66), sTNFR2 (r=0.63), TNFa (r=0.60) (all P<0.001), and ICAM-1 (r=0.41, P<0.01). In stepwise regression analyses, serum uric acid emerged as the strongest predictor of ICAM-1, interleukin-6, TNF, sTNFR1 and sTNFR2, independent of diuretic dose, age, body mass index, alcohol intake, serum creatinine, plasma insulin and glucose, and insulin sensitivity. Serum uric acid is strongly related to circulating markers of inflammation in patients with chronic heart failure. This is consistent with a role for increased xanthine oxidase activity in the inflammatory response in patients with chronic heart failure.

Involvement of Free Radicals and Histamine in the Potentiating Action of Cigarette Smoke Exposure on Ethanol-Induced Gastric Mucosal Damage in Rats

Cigarette smoking has been associated with peptic ulcer diseases. We studied the effects of cigarette smoke exposure on ethanol-induced gastric mucosal damage and its relationship with vascular integrity and the possible role of free radicals and histamine. Male Sprague-Dawley rats were exposed to cigarette smoke followed by ethanol administration (70% v/v). Smoke exposure alone dose-dependently reduced basal blood flow and increased xanthine oxidase (XO) activity but superoxide dismutase (SOD) activity remained unaffected in gastric mucosa. Cigarette smoking followed by ethanol administration significantly potentiated mucosal lesion formation along with augmentation of the mucosal blood flow, vascular permeability and myeloperoxidase (MPO) activity. The potentiating effect of smoking on ethanol-induced gastric mucosal lesion and MPO activity was abolished by pretreatment with allopurinol, terfenadine or ranitidine. Terfenadine and ranitidine also reduced the increased mucosal blood flow and vascular permeability induced by smoking and ethanol combined. These findings suggested that cigarette smoke adversely affected the defense mechanisms of the gastric mucosa by reducing the mucosal blood flow which in turn led to ischemia and increased XO activity. Activation of XO together with histamine H 1 and H 2 receptors stimulation could lead to neutrophil aggregation and vascular damage. However, the potentiating action of cigarette smoke on ethanol ulceration is unlikely through reduction of SOD activity in gastric mucosa.

Effects of cigarette smoking on gastric ulcer formation and healing: possible mechanisms of action.

Epidemiologic studies have shown that cigarette smoking is closely related to peptic ulcer disease. The mechanisms by which cigarette smoking adversely affects gastric mucosa have been suggested and elucidated. This article reviews some of the mechanisms involved in cigarette smoking-related gastric ulceration and healing. Experimental findings suggest that cigarette smoking increases xanthine oxidase activity, leukotrienes, and nitric oxide production and also neutrophil infiltration in the gastric mucosa. On the other hand, it reduces blood flow, prostaglandin production, epithelial cell proliferation, and formation of blood vessels in the tissue. These actions are important for ulcer formation and healing. The evidence thus far available strengthens the hypothesis that cigarette smoke is indeed harmful to gastric mucosa through defined mechanisms.

Drug-Cytokine Interactions

The potential for certain cytokines to alter cytochrome P450-mediated drug metabolism was first described over 20 years ago. Since that time, a number of in vitro studies in a variety of models have confirmed those observations and evaluated the possible mechanisms. Although the actual mechanism(s) remains unknown, several potential theories have been proposed, including the inhibition of mRNA transcription, increased haem oxygenase activity, increased xanthine oxidase activity and the induction of killer cells cytotoxic to liver cells containing cytochrome P450. Clinical data regarding drug-cytokine interactions are currently limited to the results of studies with small patient numbers and case reports. In addition, the results of different reports are often conflicting. Some clinical studies have reported associations between exogenous or endogenous cytokines and alterations in concomitantly administered drugs, whereas others have reported a lack of effect. Differences in cytokine dosages, route of administration, time course of therapy, sample collection times and patient variability are all likely to account for the varied results. In this rapidly expanding field, additional research will better define the mechanisms of these interactions and their clinical implications.

Increased xanthine oxidase during labour—implications for oxidative stress

Xanthine dehydrogenase/oxidase (XDH/XO) produces uric acid. When in the oxidase form, this production is coupled with the generation of free radicals. Hypoxia-reperfusion enhances conversion of XDH to XO. Since the placenta is exposed to short periods of hypoxia reperfusion during labour, 17 placentae of pregnancy terminated by elective caesarean section and five placentae of pregnancies terminated by caesarean section during labour were examined for XDH/XO activity. It was found that XO activity was higher in the placentae of labouring women ( P=0.003), which suggests that labour enhances conversion of XDH to XO, facilitating free radical production.

Induction of increased phosphatidylcholine hydroperoxide by an iron-deficient diet in rats

The effect of iron-deficiency on lipid peroxidation in male and female rats was investigated and an attempt was made to understand the underlying mechanisms based on the changes in lipid hydroperoxide formation and relevant hepatic enzymes. Forty 4-week-old male and female rats were fed either an iron-deficient diet or a control diet for 4 weeks. The amount of iron in the microsome and cytosol of liver cells decreased 84 to 55% in the iron-deficient rats, and the amount of copper increased 222 to 1206% in the subcellular fraction of the males, but it only increased 14 to 43% in the microsome and cytosol fraction in the females. Serum and liver triglycerides, phospholipid, and cholesterol increased in iron-deficient male rats, but in female, only cholesterol slightly increased. Serum and liver phosphatidylcholine hydroperoxide (PCOOH) increased 55% and 61%, respectively in the iron-deficient males, and increased less in the females (26% and 10%, respectively). Increased xanthine oxidase (XOD) activity, decreased superoxide dismutase (SOD) activity, and markedly increased glutathione peroxidase (GSH-Px) activity were observed in the liver of the males. The lower XOD and SOD activities and slightly GSH-Px in the females may explain the difference in production of PCOOH according to sex. The role of copper accumulation in the production of lipid peroxides in iron-deficient rats is discussed.