Increased Plasma Lipid Peroxidation Research Articles

Induction of oxidative stress in paraquat formulating workers

Paraquat as a bipyridyl compound is widely used as an effective herbicide worldwide. In this study, oxidative stress was investigated in blood samples of workers in a pesticide factory, formulating paraquat products for use in agriculture. Controls were age-matched workers with no history of pesticide exposure. They were measured for lipid peroxidation (LPO), antioxidant power and total thiol (SH) groups in blood. The results expressed as mean±SD show induction of oxidative stress in workers as revealed by increased plasma LPO (11.46±0.99 vs 10.11±0.69, P<0.001), decreased plasma antioxidant capacity (1.35±0.03 vs 1.54±0.05, P<0.001) and plasma SH groups (0.16±0.01 vs 0.21±0.01, P<0.001) in comparison to those of controls. It is concluded that paraquat-formulating factory workers have elevated LPO and decreased antioxidant power, which may put them in further consequences of oxidative stress.

Effects of fish oil and vitamin E on the antioxidant defense system in diet-induced hypercholesterolemic rabbits

This study was designed to investigate the effects of fish oil and vitamin E on the antioxidant defense system in hypercholesterolemic rabbits. A high fat and cholesterol diet, with or without supplement by fish oil and/or a vitamin E supplement, was fed to rabbits for 6 weeks. Compared to the reference diet of regular laboratory rabbit chow, a high fat and cholesterol-enriched diet increased atheroma formation, plasma lipid and peroxide levels, decreased blood glutathione levels, and reduced plasma glutathione reductase, glutathione peroxidase, and catalase activities. Fish oil supplementation significantly reduced atheroma and increased glutathione reductase and glutathione peroxidase activities and blood glutathione levels, but increased plasma lipid peroxide levels. Vitamin E supplementation of the fish oil diet enhanced the beneficial effects by increasing glutathione reductase activity and decreasing peroxide levels. These results indicate that a high fat and cholesterol diet attenuates blood glutathione levels and plasma antioxidant enzyme activities, which may account for some of its atherogenic properties. Consumption of fish oil enhances antioxidative defenses against the oxidative stress imposed by hypercholesterolemia, and vitamin E further enhances these beneficial effects.

Lipid hydroperoxides and free radical scavenging enzyme activities in preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome: No evidence for circulating primary products of lipid peroxidation

Objective: Preeclampsia is reportedly accompanied by increased plasma lipid peroxidation. However, to date the assays that have been applied to measure lipid peroxides have been relatively nonspecific. A highly specific high-performance lipid chromatographic–chemiluminescence technique was used here to measure lipid hydroperoxides in plasma and red blood cells of patients with preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Study Design: Lipid peroxidation products, both lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS), and free radical scavenging enzyme activities were measured in either plasma or erythrocytes of patients with normal pregnancies (n = 36), preeclampsia (n = 28), or HELLP syndrome (n = 10). Results: Whereas lipid hydroperoxides were undetectable (<0.02 μmol/L), plasma TBARS and glutathione peroxidase activity in plasma and erythrocytes were significantly increased in patients with HELLP syndrome. There were no differences in glutathione transferase and reductase activities or superoxide dismutase activity between the groups. Conclusions: We were unable to corroborate results of studies that suggested that increased TBARS are representative of circulating plasma lipid hydroperoxides in preeclampsia. However, elevated glutathione peroxidase activity and TBARS are in line with increased oxidative stress in preeclampsia. (Am J Obstet Gynecol 2001;185:166-72.)

Brains of aged apolipoprotein E-deficient mice have increased levels of F2-isoprostanes, in vivo markers of lipid peroxidation.

Apolipoprotein E (apoE) is the major apolipoprotein of the CNS. Differential expression of apoE isoforms has been linked to longevity and to the pathogenesis of Alzheimer's disease. Several studies have demonstrated that this glycoprotein is important in mature as well as in aging CNS, where it may serve neurotrophic and/or neuroprotective functions. Some reports have shown that apoE-deficient mice have age-dependent neurodegeneration and cognitive impairment; others have not confirmed these observations. ApoE-deficient mice also develop hypercholesterolemia on a chow diet and have in vivo increased plasma lipid peroxidation products. F2-isoprostanes are prostaglandin F2alpha isomers and chemically stable peroxidation products of arachidonic acid. Both isoprostane F2alpha-III and isoprostane F2alpha-VI were markedly elevated in the brains of aged apoE-deficient mice compared with either wild-type C57 Bl/6 mice or a distinct mouse model of hypercholesterolemia, the low-density lipoprotein receptor-deficient mouse. By contrast, no difference in isoprostane levels was observed in young apoE-deficient mice compared with age-matched wild-type control mice. Our findings indicate that disorder of lipid metabolism in the absence of apoE can induce an age-dependent increase in brain lipid peroxidation products.

Melatonin and taurine reduce early glomerulopathy in diabetic rats

Oxidative stress occurs in diabetic patients and experimental models of diabetes. We examined whether two antioxidants, melatonin and taurine, can ameliorate diabetic nephropathy. Enhanced expression of glomerular TGF-β1 and fibronectin mRNAs and proteinuria were employed as indices of diabetic nephropathy. Experimental diabetes was induced by intravenous injection of streptozotocin 50 mg/kg. Two days after streptozotocin, diabetic rats were assigned to one of the following groups: i) untreated; ii) melatonin supplement by 0.02% in drinking water; or iii) taurine supplement by 1% in drinking water. Four weeks after streptozotocin, diabetic rats ( n = 6: plasma glucose 516 ± 12 mg/dl) exhibited 6.1 fold increase in urinary protein excretion, 1.4 fold increase in glomerular TGF-β1 mRNA, 1.7 fold increase in glomerular fibronectin mRNA, 2.2 fold increase in plasma lipid peroxides (LPO), and 44 fold increase in urinary LPO excretion above the values in control rats ( n = 6: plasma glucose 188 ± 14 mg/dl). Chronic administration of melatonin ( n = 6) and taurine ( n = 6) prevented increases in glomerular TGF-β1 and fibronectin mRNAs and proteinuria without having effect on blood glucose. Both treatments reduced lipid peroxidation by nearly 50%. The present data demonstrate beneficial effects of melatonin and taurine on early changes in diabetic kidney and suggest that diabetic nephropathy associated with hyperglycemia is largely mediated by oxidative stress. Science

Protective effect of dietary tomato against endothelial dysfunction in hypercholesterolemic mice.

The effects of dietary ingestion of tomato were studied in mice that had been made hypercholesterolemic by feeding atherogenic diets. Mice which had been fed on the atherogenic diet without tomato for 4 months had significantly increased plasma lipid peroxide, and the vaso-relaxing activity in the aorta induced by acetylcholine (ACh) was harmed when compared with mice fed on a common commercial diet. On the other hand, mice which had been fed on the atherogenic diet containing 20% (w/w) lyophilized powder of tomato showed less increase in the plasma lipid peroxide level, and ACh-induced vaso-relaxation was maintained at the same level as that in normal mice. These results indicate that tomato has a preventive effect on atherosclerosis by protecting plasma lipids from oxidation.

High Dietary Intake of Vitamin E Causes Lowered Total Plasma Oxidation In Hypercholesterolemic Rats

Oxidative stress appears to play a key role in the development of atherosclerosis. Patients with cardio-vascular diseases have increased plasma lipid peroxides. Low-density lipoprotein cholesterol (LDL) in plasma must undergo oxidative modification before giving rise to foam cells, one of the earliest stages in the development of atherosclerosis. Epidemiological evidence suggests that high dietary intake of vitamin E may protect plasma from oxidation, thereby reducing the risk for heart disease. To test this hypothesis, five groups of hypercholesterolemic rats were fed diets containing various amounts of vitamin E, ranging from zero milligrams (deficient diet) to 2400 milligrams (high level supplementation). Total plasma oxidation was determined by measuring the formation of malondialdehyde (a lipid peroxidation product) at baseline and after inducing iron-catalyzed lipid peroxidation. The results are summarized below: Vitamin E Malondialdehyde formation (mg/kg diet) (nmol/ml plasma) Baseline Oxidation Group I 60 3.636 5.395 Group II 0 6.673 23.197 Group III 300 8.252 22.358 Group IV 600 7.532 15.864 Group V 2400 8.392 13.896 (Group I - no cholesterol control diet) KEY FINDINGS: Upon iron-induced oxidation, MDA formation from baseline values was highest in the animals that were vitamin E deficient (group II). The formation of MDA decreased steadily from baseline values as vitamin E levels went higher. Decreased MDA formation in group I could be due to the low cholesterol substrate levels available for oxidation. It appears that high levels of vitamin E supplementation may exert a protective effect by decreasing lipid peroxidation, thereby reducing the oxidative stress.

Plasma Proteins in Acute and Chronic Lung Disease of the Newborn

This study compared plasma levels of albumin, transferrin, and ceruloplasmin in well preterm babies ( n = 21) with those with respiratory distress syndrome (RDS, n = 13) and chronic lung disease (CLD, n = 13) over the first 28 postnatal days. Plasma lipid peroxidation, total radical trapping capacity (TRAP assay), and iron binding antioxidant capacity were also measured. In RDS and CLD albumin levels were decreased on days 1, 4 and 10; on day 10 albumin was lower in CLD compared to RDS ( p < .05). After day 10 the levels were similar in all groups. The transferrin levels showed a similar trend. Ceruloplasmin levels did not differ, except for a higher day 28 level in CLD ( p < .05). Albumin levels significantly decreased with increasing FiO 2 and duration of oxygen therapy (within patient r = −0.30, p < .05 and r = −0.51, p < .005, respectively). On day 10, increasing oxygen therapy increased plasma lipid peroxidation ( r = +0.49, p < .01), which was also significantly related to lower plasma protein levels ( r = −0.42, p < .01). Lower plasma albumin and transferrin lowered the TRAP and iron binding antioxidant capacity, respectively ( r = +0.36, p < .05, and r = +0.41, p < .005). Prediction of CLD using day 10 albumin levels had a specificity of 94%, but a sensitivity of only 50%. The interaction between oxygen toxicity and high ventilation pressures in immature babies appears to lower plasma proteins by increasing pulmonary permeability. The lower plasma albumin level was not useful in predicting the development of CLD; however, the fall in plasma transferrin and albumin will further decrease the preventive and chain-breaking antioxidant capacity of plasma of these ill babies.

Elevated Plasma Lipid Peroxides at the Onset of Nonaffective Psychosis

Background: Impaired antioxidant defense and increased lipid peroxidation has been reported in chronic schizophrenic patients. Recently, we have reported an impaired antioxidant defense in never medicated first-episode schizophrenic and schizophreniform patients. We report now a concomitant increase in plasma lipid peroxides. Methods: The plasma lipid peroxides [thiobarbituric acid reactive substances (TBARS)] were analyzed by chemical and high performance liquid chromatography procedures in 26 patients admitted for a first episode of schizophrenic ( N = 17) or schizophreniform psychosis ( N = 9) and 16 normal control subjects. The patients had a duration of 4.5 days (SD 2.8) of psychosis at the time of the study. Results: Plasma TBARS levels were significantly higher in the patients than in normal controls ( P < .002). TBARS levels were above the normal range in 16 of the 26 patients. Higher TBARS levels were associated with a greater severity of negative symptoms and lower red blood cell activity of the glutathione peroxidase. Conclusions: The findings indicate ongoing oxidative injury at the very onset of psychosis. If valid, this would indicate the need for adjunctive antioxidant treatment from the beginning of the course of nonaffective psychoses. This might prevent a deteriorating course and development of the deficit syndrome.

Elevated plasma lipid hydroperoxides in patients with coronary artery disease

Sustained presence of lipid peroxides in the circulation and their plasma carrier is a controversial issue. Particularly, there is no firm evidence for an increased plasma lipid peroxide level in patients with atherosclerosis. In this study, a strong correlation was found between plasma total lipid hydroperoxide and lipid hydroperoxide content of LDL cholesterol ( r = 0.882; p < 0.001; n = 16). Lipid hydroperoxides in plasma were carried almost exclusively (89%) in LDL. In 70 patients tested 3 months after coronary artery bypass graft surgery with a specific assay, plasma lipid hydroperoxide levels were significantly increased when compared with matched healthy controls (4.31 ± 0.23 nmol/ml and 2.34 ± 0.13 nmol/ml, p < 0.0001, patients vs controls, respectively). These concentrations are 10 times lower than those detected by the nonspecific thiobarbituric acid assay. However, considering the in vitro concentration range in which oxidized LDL exerts important atherogenic effects, the elevated plasma lipid hydroperoxide levels measured in atherosclerotic patients have pathologic significance. (Am Heart J 1997;134:572-6.)

Dietary selenium increases cellular glutathione peroxidase activity and reduces the enhanced susceptibility to lipid peroxidation of plasma and low-density lipoprotein in kidney transplant recipients.

The glutathione system plays a major role in the protection of cells against oxidative stress in humans. The aim of the present study was to find out the relationship between the glutathione system and plasma lipid peroxidation in six renal transplant recipients (who are under oxidative stress and thus at high risk for atherosclerosis), by using dietary selenium to activate the glutathione system. 2,2'-Azobis-2-amidinopropane hydrochloride (AAPH)-induced plasma lipid peroxidation was increased (by 60%) in all six patients in comparison to normal subjects. A similar pattern of increased plasma lipid peroxidation was found even in the basal state (in the absence of added AAPH). CuSO4-induced low-density lipoprotein (LDL) oxidation measured by peroxide formation was also significantly increased by 2.3-fold in the patients' LDL in comparison to normal LDL. Even in the absence of CuSO4, the LDL oxidation state was also increased in the patients' LDL in comparison to normal LDL. We thus analyzed the effect of dietary selenium (0.2 mg/day for a period of 3 months, followed by an additional 3 months on placebo) on plasma and on LDL lipid peroxidation. Selenium treatment resulted in a 50% reduction in AAPH-induced plasma lipid peroxidation. The susceptibility of the patients' plasma to lipid peroxidation returned toward baseline values 3 months after termination of the selenium treatment. Similar results, although less pronounced (only 15% reduction), were obtained for CuSO4-induced LDL oxidation. Analyses of the patients' red blood cell (RBC) glutathione system revealed low levels of reduced glutathione and decreased activities of RBC glutathione peroxidase and glutathione reductase by 23%, 18%, and 20%, respectively, in comparison to normal RBC. Selenium treatment resulted in a significant elevation of RBC glutathione peroxidase and glutathione reductase activities and in reduced glutathione content by 64%, 57%, and 11%, respectively; this effect was also paralleled by a 39% reduction in the RBC oxidized glutathione content. On termination of the selenium treatment, and after 3 months on placebo, all of these values of the glutathione system elements returned toward baseline levels. We thus conclude that dietary selenium, which activates the glutathione system, is a potent antioxidant against plasma and LDL lipid peroxidation in renal transplant recipients, and may thus be considered antiatherogenic.

Chronic treatment with the 21-aminosteroid U74389F, an inhibitor of lipid peroxidation, does not prevent diabetic endothelial dysfunction.

Oxygen-derived free radicals are believed to be involved in diabetes-induced vascular complications. The role of oxygen radicals in endothelial dysfunction in diabetes is not known with certainty. In this study we tested whether inhibition of lipid peroxidation using the potent inhibitor U74389F, a 21-aminosteroid also known as lazaroid, could prevent endothelial dysfunction in diabetes. Lewis strain rats were made diabetic by intravenous injection of streptozotocin. A subgroup of diabetic animals received daily oral doses of 10 mg/kg U74389F at 72 hours post streptozotocin and throughout the 8-week duration of diabetes. Thoracic aortas were isolated and suspended in isolated tissue baths and contracted with norepinephrine. Relaxation due to the endothelium-dependent vasodilator, acetylcholine, was impaired in diabetic aorta while relaxation due to A23187 and nitroglycerin was unaltered. Chronic treatment of diabetic animals with U74389F normalized the increase in plasma lipid peroxides as assessed by thiobarbituric acid-reactive substances but did not alter serum insulin levels, blood glucose concentration, nor total glycosylated hemoglobin. Increases in aortic catalase activity resulting from diabetes was not altered by U74389F. Despite reductions in lipid peroxides, U74389F did not prevent the diabetes-induced impairment in endothelium-dependent relaxation caused by acetylcholine. These data suggest that other pathways that are antecedent to lipid peroxidation may be responsible for endothelial dysfunction in diabetes.

Oxidative injury and potential use of antioxidants in schizophrenia

There is increasing evidence that oxidative injury contributes to pathophysiology of schizophrenia, indicated by the increased lipid peroxidation products in plasma and CSF, and altered levels of both enzymatic and non-enzymatic antioxidants in chronic and drug-naive first-episode schizophrenic patients. The increased plasma lipid peroxidation is also supported by concomitant lower levels of esterified polyunsaturated essential fatty acids of red blood cell plasma membrane phospholipids. Because membrane phospholipids play a critical role in neuronal signal transduction, oxidative damage of these lipids may contribute to the proposed altered neurotransmitter receptor-mediated signal transduction and thereby alter information processing in schizophrenia. Adjunctive treatment with antioxidants (e.g. vitamins E and C, β-carotene and quinones) at the initial stages of illness may prevent further oxidative injury and thereby ameliorate and prevent further possible deterioration of associated neurological and behavioral deficits in schizophrenia.

Increased plasma lipid peroxidation in patients with aceruloplasminemia

Aceruloplasminemia is a newly recognized autosomal recessive disorder of iron metabolism due to mutations in the ceruloplasmin gene. Although the presence of these mutations reveals an essential role for ceruloplasmin in human biology, the mechanisms of tissue injury in this disease are unknown. We report here on the identification of increased plasma lipid peroxidation in multiple affected family members with aceruloplasminemia. Consistent with the absence of serum ceruloplasmin, plasma ferroxidase activity was markedly reduced and serum ferritin was significantly increased. Plasma lipid peroxidation was determined as thiobarbituric acid-reactive products (TBA products) in plasma samples from control, heterozygote, and affected patients. Basal levels of lipid peroxides were three times control values in patients with aceruloplasminemia and were significantly increased in these patients in the presence of copper ions and hydrogen peroxide. In each case these increases were suppressed by the addition of exogenous ceruloplasmin. These data suggest that increased susceptibility to lipid peroxidation may contribute to the unique neuropathology observed in patients with aceruloplasminemia and imply a role for free radical-mediated tissue injury in degenerative disorders of the basal ganglia.

Plasma 8-epi-PGF 2α levels are elevated in individuals with non-insulin dependent diabetes mellitus

This study reports plasma levels of a specific nonenzymatic peroxidation product of arachidonic acid, esterified 8-epi-PGF 2α, from healthy- and NIDDM individuals as an index of oxidative stress in vivo. Plasma 8-epi-PGF 2α was isolated by solid-phase extraction on a C,8 followed by an NH 2 cartridge and analyzed by GC-MS/NICI as PFB-ester/TMS-ether derivative. We found that the average concentration of esterified 8-epi-PGF 2α among NIDDM subjects (0.93 ± 0.07 nM, n = 39) was higher ( P < 0.0001, Mann-Whitney test) than in healthy individuals (0.28 ± 0.04 nM, n = 15). These data indicate that NIDDM is associated with increased plasma lipid peroxidation.

Susceptibility of plasma to ferrous iron/hydrogen peroxide-mediated oxidation: demonstration of a possible Fenton reaction

The aim of our study was to evaluate a model system by using iron in the peroxidation of plasma. Lipid peroxidation was monitored by fluorometric measurement of lipid peroxides (LPO). Plasma coincubated with Fe2+ and H2O2 had a 268% increase in plasma LPO after 1 h. The optimum concentrations were 0.42 mmol/L Fe2+ and 0.73 mol/L H2O2. Coincubation of plasma with these concentrations of Fe2+ and H2O2 separately resulted in no increase in plasma LPO. The increase in plasma LPO after oxidation with Fe2+/H2O2 was paralleled by a decrease in plasma polyunsaturated fatty acids, an increase in the relative electrophoretic mobility of low-density lipoprotein (LDL), and decreases in apolipoprotein (apo) B-100 and apo A-I immunoreactivity. In vitro oxidation of LDL and high-density lipoprotein separately with this system produced increases of LPO of 246% and 128%, respectively. LPO formation in plasma was inhibited by catalase, desferrioxamine, and mannitol, but not by superoxide dismutase. Hydroxyl radical generation with Fe2+/H2O2 was evidenced by fragmentation of deoxyribose. We conclude that the Fe2+/H2O2 system, possibly by a Fenton reaction mechanism, resulted in significant plasma oxidation. This model system may be useful for examining lipid peroxidation in clinical investigations.

Activation of the phagocytic system increases intimal proliferation in hypercholesterolemic rabbits

The effect of in vivo stimulation of the phagocytic system (neutrophils, monocytes and hepatic Kupffer-cells) by inducing phagocytosis of intravenously administered latex particles on lipid peroxidation and aortic intimal proliferation was tested in cholesterol-fed rabbits. Three weeks after starting the diet, aortic intimal proliferation was measured by the intimal to medial ratios and by the incorporation of [ 3H]thymidine, infused into the circulation for the preceding 14 days. Intimal to medial ratios were increased (0.473 ± 0.023 vs. 0.282 ± 0.011, P < 0.01) and aortic [ 3H]thymidine contents were higher (66.8 ± 3.5 vs. 27.8 ± 49 counts/min per mg, P=0.0001) in latex bead-treated than in control animals. Injection of beads transiently increased plasma lipid peroxide levels. At the end of the 3 week experiment, plasma lipid peroxide levels were still elevated and lipid peroxide contents of the aortic walls were higher in the latex-treated rabbits (82.8 ± 5.8 vs. 46.4 ± 4.9 nmol/mg cholesterol, latex-treated vs. controls, P = 0.004). These data suggest a significant acceleration of atherogenesis by the stimulated phagocytic system, the mechanism of which may involve lipid peroxidation.

Preservation of endothelium-dependent relaxation in atherosclerotic rabbit aorta by probucol.

Oxidized low-density lipoproteins (LDL), which may play an important role in atherogenesis, inhibit endothelium-dependent relaxations of normal arteries in vitro. The effects of probucol, an inhibitor of LDL oxidation, on endothelium-dependent relaxations in thoracic aorta of rabbits that received a cholesterol-rich (0.5%) or standard diet for 10 weeks were determined. In some rabbits in each group, the diet was supplemented with probucol (1%) for the last 6 weeks. The cholesterol-rich diet markedly increased plasma cholesterol and resulted in increased plasma lipid peroxides. Probucol prevented the increase in lipid peroxides, but had no effect on plasma cholesterol. Rings of aorta were mounted in organ chambers for measurement of isometric tension and contracted with phenylephrine. Endothelium-dependent relaxations to acetylcholine and A23187 were significantly impaired in aortic rings from cholesterol-fed rabbits. Aortic rings from rabbits fed cholesterol and treated with probucol relaxed normally to both vasodilators. Relaxations to acetylcholine and A23187 were not significantly changed in rings from rabbits that received probucol-supplemented standard diet. Endothelium-independent relaxations to sodium nitroprusside (SNP) were not influenced by the cholesterol diet or probucol. Thus, probucol preserves endothelium-dependent relaxations of hypercholesterolemic rabbit aorta without reducing plasma cholesterol. As demonstrated by the reduction in plasma lipid peroxides, the effect of probucol may be related to its antioxidant properties and may imply that oxidized lipids have a role in endothelial cell dysfunction of atherosclerotic arteries in vivo.

Inhibitory Effect of Taurine on Puromycin Aminonucleoside-Induced Hyperlipidemia in Rats.

The protective effects of taurine on hyperlipidemia associated with puromycin aminonucleoside-induced nephrotis were assessed in male Wistar rats. Administration of puromycin aminonucleoside to rats resulted in hyperlipidemia at the end of 10 days, as indicated by significant elevation of cholesterol, triglycerides, and phospholipids in plasma and liver. A significant increase in plasma lipid peroxides associated with lipoprotein fractions was observed in nephrotic rats. Liver lipids and lipid peroxides were also higher in these animals. On the other hand, reduced lipoprotein lipase activity was noted in liver of the puromycin-treated rats. In addition, urinary excretion of cholesterol was also high in them. However, treatment of the nephrotic rats with taurine modified hyperlipidemia with reduction in lipid peroxide and all major lipoprotein fractions. Taurine significantly prevented the decrease in lipoprotein lipase activity induced by puromycin. Therefore, our results suggest that prevention of hyperlipidemia by taurine contributes to its therapeutic effects in attenuating the puromycin-induced nephrotic syndrome.

Levels of plasma lipid peroxides before and after choledocholithotomy in patients with obstructive jaundice.

Plasma lipid peroxide levels were measured in a group of 40 healthy controls and 11 patients with jaundice. In the case of these 11 patients, we checked the plasma lipid peroxide concentrations prior to and after choledocholithotomy. Before choledocholithotomy, there were significantly higher mean concentrations of plasma lipid peroxides and bilirubin in patients with jaundice than in the control cases (11.8 +/- 2.3 vs. 2.0 +/- 0.1 nmol/ml and 10.3 +/- 1.82 vs. 0.7 +/- 0.03 mg/dl, respectively, P < 0.05). In addition, patients with jaundice had lower plasma vitamin E levels in comparison to the controls (8.2 +/- 0.6 vs. 12.2 +/- 0.5 micrograms/ml, P < 0.05). In patients with jaundice, the increased plasma lipid peroxides were clearly related to the serum levels of bilirubin (r = 0.87, P < 0.05). After surgery, the higher plasma levels of lipid peroxide and bilirubin were reduced markedly (11.8 +/- 2.3 vs. 3.7 +/- 0.4 nmol/ml and 10.3 +/- 1.82 vs. 3.1 +/- 0.47 mg/dl, respectively, P < 0.05) with the restoration of bile flow which was associated with improvement in liver function tests. Consequently, these results suggest that there is an involvement of lipid peroxidation in liver cells damaged by obstructive jaundice in patients with cholelithiasis, and that these high plasma lipid peroxide levels may correlate with the severity of the disease.