The importance of paraoxonase 1 activity, nitric oxide and lipid peroxidation in hepatosteatosis

This study evaluated the changes in oxidative status in hepatosteatosis patients in terms of lipid peroxidation, nitric oxide (NO) and paraoxonase 1 (PON1) activity. A total of 49 patients with hepatosteatosis (29 males and 20 females, mean age 47.2 +/- 3.6 years) and 25 healthy subjects (15 males and 10 females, mean age 46.1 +/- 3.2 years) were enrolled in the study. Serum PON1 was measured spectrophotometrically, malondialdehyde (MDA), an end-product of lipid peroxidation, was determined using the thiobarbituric acid method, and NO was assessed using the Griess reaction. Lipid and other biochemical parameters were determined by routine laboratory methods. PON1 activity and NO levels were significantly decreased and MDA levels significantly increased in hepatosteatosis patients compared with healthy subjects. PON1 activity was correlated with MDA level and NO level. In conclusion, oxidative stress seems significantly to suppress PON1 synthesis in hepatosteatosis patients. In addition, oxidative stress and oxidant-antioxidant imbalance may be part of the cytotoxic mechanisms leading to liver cell injury.     

Assessment of paraoxonase 1 activity and malondialdehyde levels in patients with rheumatoid arthritis

OBJECTIVES: We aimed to evaluate antioxidant paraoxonase 1 activity together with malondialdehyde (MDA) (an oxidative stress parameter) levels in patients with rheumatoid arthritis. DESIGN AND METHODS: Fifty-seven rheumatoid arthritis patients were included in the study and subgrouped according to disease activity (active, n = 31; inactive, n = 26) and compared with healthy controls (n = 25). Serum paraoxonase 1 activity and MDA levels were measured according to an enzymatic spectrophotometric method. RESULTS: Serum MDA level was higher (P = 0.001) whereas paraoxonase 1 activity was lower (P = 0.001) in the patient group than the controls. When active and inactive subgroups were compared with the control group, there was a statistically significant difference between each parameter. Serum MDA levels were significantly higher, while paraoxonase 1 activity was lower in the active and inactive rheumatoid arthritis groups than the control group. But there was not any difference between active and inactive patients with RA. There was a negative correlation between MDA levels and paraoxonase 1 activity. CONCLUSIONS: Increased reactive oxygen species levels in rheumatoid arthritis may result in a pro-oxidation environment, which in turn could result in decreased antioxidant paraoxonase 1 activity and increased MDA levels.     

Effect of hyperketonemia on plasma lipid peroxidation levels in diabetic patients.

OBJECTIVE: This study was undertaken to examine the effect of ketosis on plasma lipid peroxidation levels in diabetic patients. RESEARCH DESIGN AND METHODS: Plasma levels of lipid peroxidation products (malondialdehyde) and ketone bodies (acetoacetate and beta-hydroxybutyrate) were determined in diabetic patients (n = 70) and age-matched normal volunteers (n = 25). Diabetic patients with total ketone body levels > 1.0 mmol/l were considered hyperketonemic, and those with levels < or = 1.0 mmol/l were considered normoketonemic. RESULTS: After normalization versus total lipids, levels of lipid peroxidation were significantly higher in the plasma of hyperketonemic diabetic patients (P < 0.05), but not in normoketonemic diabetic patients, compared with age-matched normal volunteers. In addition, low ketonemia was associated with lower lipid peroxidation levels when lipid peroxidation and ketonemia were determined in the same patient (n = 7) at two different clinic visits. CONCLUSIONS: This study demonstrated an association between hyperketonemia and increased lipid peroxidation levels in diabetic patients, which suggests that ketosis is a risk factor in the elevated lipid peroxidation levels associated with diabetes. Further investigation is needed to determine whether antioxidant supplementation can be particularly beneficial in reducing lipid peroxidation and complications in type 1 diabetic patients who frequently encounter ketosis.     

Serum paraoxonase activity and the extent of lipid peroxidation are not affected by increased levels of human apolipoprotein A-I: studies in transgenic mice.

The present study analyzed the effect of increased concentrations of human apolipoprotein (apo) A-I in transgenic mice serum on paraoxonase activity and on lipid peroxidation. In the transgenic mice serum, in comparison to control (non-transgenic) C57BL/6 mice, we found high concentrations of human apoA-I and high-density lipoprotein (HDL)-cholesterol, but serum lipid peroxidation (basal and free radical-induced) and serum paraoxonase activity were similar in the two mouse groups. Comparing the individual results, no significant correlation was found between free radical-induced serum lipid peroxidation and apoA-I concentrations. Serum paraoxonase activity also did not correlate with serum concentrations of human apoA-I. However, a significant inverse relationship (R2=0.75) was observed between the individual values of paraoxonase activity and free radical-induced lipid peroxidation in both mouse groups. Direct analysis of the effect of pure human apoA-I and paraoxonase (using the specific paraoxonase inhibitor PD-92770) on lipid peroxidation also revealed that paraoxonase, but not apoA-I, protects serum lipids from oxidation. We thus conclude that the increased human apoA-I concentration in the mouse serum neither affect serum paraoxonase activity, nor protects against lipid peroxidation, whereas paraoxonase significantly inhibits serum lipid peroxidation.     

Amino acid concentrations in serum and aqueous humor from subjects with extreme myopia or senile cataract

With an amino acid analyzer, we measured amino acids and related compounds in serum and aqueous humor from normal Chinese and some patients with extreme myopia or senile cataracts. Forty peaks were well resolved, and their areas were used to quantify each compound. In the myopic patients, glutamate, alpha-aminoadipate, and methionine concentrations in serum were 10-fold those in the normal subjects. Values for most of the other amino acids and related compounds were also higher in myopic patients' sera. In the cataract patients, concentrations of most of these compounds were lower in serum but higher in aqueous humor than for the normal subjects. Tryptophan was present in significant amounts in sera from the normal subjects, but was not detectable in the senile-cataract patients. The ratio of amino acid concentration in aqueous humor to that in the serum (Ch/Cs) was higher in the cataract patients than in normal subjects for almost all of the compounds we measured.     

Platelet monoamine oxidase activity and plasma levels of non-catecholic phenylethylamines in insulin-dependent diabetic subjects

The activity of blood platelets monoamine oxidase (MAO) was significantly reduced in a group of insulin-dependent diabetics when compared to sex- and age-matched controls. This enzymatic change was accompanied by a dramatic increase in the plasma levels of phenylethylamine, whereas no significant changes were observed for the concentration of either p-tyramine or phenylethanolamine. Levels of the o- and m-isomers of tyramine were below detectable limit (< 0.050 ng/ml). A possible role of the MAO/monoamine system in the pathophysiology of diabetes is discussed.     

Clinico-diagnostic evaluation of changes in ATPase activity, lipid peroxidation and stability of red cell membranes in patients suffering from hemorrhagic fever with renal syndrome

AIM: To examine morphofunctional and metabolic features of erythrocytes affecting blood rheology in patients with hemorrhagic fever with renal syndrome (HFRS) for assessment of the disease severity. MATERIAL AND METHODS: 130 HFRS patients were examined using clinical, laboratory, serological tests and fluorescent antibody test. Activity of transport ATPase and content of lipid peroxidation (LPO) products in erythrocyte membranes were measured. These membranes stability was assessed by osmotic and acid resistance in different disease periods. RESULTS: Inhibition of Na+, K+, Ca+ active ATPase of erythrocyte membrane occurred in all the examinees, LPO products rose. The membrane stability was more disturbed in moderate and severe HFRS, especially in polyuretic period. CONCLUSION: Depression of ATPase activity, growth of LPO content in erythrocytes, their relationships can be used as indicators of red cell metabolic disorders, abnormal blood rheology, and eventually, in the disease prognosis. Early membrane defects detected by osmotic and acid resistance can improve the disease diagnosis and provide data on the condition's severity.     

Serum levels of lipids, lipoproteins and paraoxonase activity in pre-eclampsia

Serum paraoxonase 1 (PON1) activity and the oxidation of lipoproteins were investigated in 35 women with pre-eclampsia and in 35 healthy control women with normal pregnancies. Blood pressure, body mass index (BMI), serum levels of total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and lipoprotein (a) (Lp[a]), and PON1 activity were assessed. There were no significant between-group differences in subject age, gestational age at diagnosis of pre-eclampsia, BMI, serum total cholesterol, triglycerides, LDL and ApoB levels. Mean systolic and diastolic blood pressures and serum Lp(a) were significantly higher in subjects with pre-eclampsia than in controls. Mean serum HDL, ApoA1 and PON1 activity were significantly lower in subjects with pre-eclampsia compared with controls. In conclusion, lipids and oxidized lipoproteins may play important roles in the pathogenesis of pre-eclampsia.     

对氧磷脂酶家族与2型糖尿病及血管并发症关系的研究

目的研究对氧磷脂酶-1(PON1)活性与2型糖尿病大中血管及微血管病变的关系及丙二醛(MDA)水平的变化。方法用紫外分光光度法测定正常对照组(NC),2型糖尿病组(DM),2型糖尿病血管并发症组血清PON1活性及MDA水平。结果PON1活性在各组分别为:正常对照组(163.84±62.98)kU/L,2型糖尿病组(118.87±30.38)kU/L,并发冠心病组(DMCHD)(95.83±23.76)kU/L,并发脑梗死组(DMCI)(94.46±24.36)kU/L,并发肾病组(DN)(106.93±20.21)kU/L,并发肾病视网膜病变组(DNDR)(100.13±24.42)kU/L(P<0.01);MDA水平在各组分别为:NC组(3.48±0.50)μmol/L,DM组(4.02±0.75)μmol/L,DMCHD组(4.67±0.74)μmol/L,DMCI组(4.55±1.39)μmol/L,DN组(3.95±0.62)μmol/L,DNDR组(4.30±0.43)μmol/L(P<0.01)。结论与正常对照组相比,2型糖尿病组PON1活性降低,MDA水平升高;血管并发症组PON1活性更低而MDA水平进一步升高,说明2型糖尿病的脂质过氧化增加,血清PON1活性下降,并参与2型糖尿病及血管并发症的发生。     

Antioxidant parameters and lipid peroxidation in salivary glands of streptozotocin-induced diabetic rats

BACKGROUND: There is evidence suggesting an unbalance between oxidant and antioxidant status associated with diabetes. Considering that salivary function is essential for the maintenance of oral and systemic health, this study was designed to examine the levels of reduced and oxidized glutathione and the activities of the antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, in salivary gland of streptozotocin-induced diabetic rats. METHODS: The content of malondialdehyde was determined in the blood and in the salivary glands. The antioxidant status was investigated in the submandibular and parotid salivary glands. RESULTS: Diabetic rats showed an increase in the content of malonaldehyde in the blood and in the submandibular salivary gland, but not in the parotid gland. Both forms, reduced and oxidized glutathione content present higher values in the diabetic submandibular gland compared with controls. No difference in the activity of superoxide dismutase between the diabetic and control glands was observed in either gland. Catalase showed higher specific activity in the parotid gland of the diabetic rats than control; however, in the submandibular gland, only when expressed as unit per gland was it higher than control. The specific activity of glutathione peroxidase was higher in the diabetic parotid gland than control; however, in the submandibular gland, its activity per gland was lower than controls. CONCLUSION: The streptozotocin-induced diabetes in rats caused different results comparing the submandibular and parotid salivary glands.     

Decreased neutrophil antioxidative enzyme activities and increased lipid peroxidation in hyperlipoproteinemic human subjects

Neutrophils have the capacity to produce free radicals. Free radicals are associated with hyperlipoproteinemia and atherosclerotic processes. For this reason, neutrophil superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GR), catalase (Cat) activities and thiobarbituric acid reactive substances (TBARS), as an index of lipid peroxidation, have been studied in hyperlipoproteinemic (HLP) and age-matched normolipidemic groups. Lipid parameters including triglycerides, total cholesterol, plasma TBARS, HDL-cholesterol, LDL-cholesterol, apo A-I, apo B have also been determined. Forty subjects (females 18, males 22) with HLP (mean age 43.8+/-8.7 (S.D.)) and 40 normolipoproteinemic subjects (females 17, males 23; mean age 46.4+/-11) were included in the study. Neutrophils were isolated by Percoll gradient centrifugation from venous blood samples. Methods used were as follows: INT method for SOD, UV method at 340 nm based on oxidation of NADPH for GSH-Px and GR, UV method at 240 nm based on degradation of hydrogen peroxide for catalase, and a method based on reaction with thiobarbituric acid for TBARS. Neutrophil SOD, GSH-Px, and catalase activities were found to be significantly low in the hyperlipoproteinemic group compared with the normolipoproteinemic group. GR activity did not differ between both groups. The mean TBARS level in the neutrophil fraction was found to be significantly higher in hyperlipoproteinemics than in that of the normolipoproteinemics. It was concluded that decreased neutrophil antioxidant enzyme activities in hyperlipoproteinemics may lead to insufficient detoxification of free radicals produced in these cells and contribute to increased lipid peroxidation.     

2型糖尿病患者血清瘦素水平的分析

目的:通过2型糖尿病患者与正常对照者之间的比较,分析血清瘦素与多种影响因素的关系。方法:对样本人群进行流行病学问卷调查、体检并测定了血糖、血脂、胰岛素和血清瘦素等生化指标,通过病例对照研究方法加以分析。结果:2型糖尿病患者血清瘦素为(9.43±6.15)ng/ml,正常对照为(9.48±5.60)ng/ml。无论有无糖尿病肥胖者血清瘦素约是非肥胖者的2倍,女性约是男性的3倍。结论:2型糖尿病患者与正常对照者间的血清瘦素不存在显著性差异,可能与患者坚持治疗病情控制良好有关。血清瘦素受到吸烟、性别、体脂、血脂和饮食等多方面因素的共同影响,高密度脂蛋白胆固醇可能是其保护因素。     

Amino acids levels and lipid peroxidation in maple syrup urine disease patients

Objective

In the present study we correlated the amino acids, branched-chain α-keto acids and α-hydroxy acids levels with the thiobarbituric acid-reactive species (TBARS) measurement, a lipid peroxidation parameter, in plasma from treated MSUD patients in order to examine whether these accumulated metabolites could be associated to the oxidative stress present in MSUD.

Design and methods

TBARS, amino acids, branched-chain α-keto acids and α-hydroxy acids concentrations were measured in plasma samples from treated MSUD patients.

Results

We verified that plasma TBARS was increased, whereas tryptophan and methionine concentrations were significantly reduced. Furthermore TBARS measurement was inversely correlated to methionine and tryptophan levels.

Conclusions

Considering that methionine and tryptophan have antioxidant activities, the data suggest that the imbalance of these amino acids may be involved with lipid peroxidation in MSUD.     

大强度运动大鼠血脂和过氧化水平变化与白藜芦醇的影响

目的:大强度运动不利于人体脂蛋白的改善,只有低强度、长时间的有氧运动能有效地改善脂蛋白水平,防止疾病的发生.实验观察白藜芦醇对大强度运动训练大鼠血浆脂质过氧化水平和血脂含量的影响.方法:实验于2004-03/06在陕西师范大学运动人体科学实验室完成.①实验动物:选择雄性SD大鼠30只,随机分为对照组、运动组、白藜芦醇 运动组,每组10只.实验过程中对动物处置符合动物伦理学要求.②实验方法:运动组大鼠于动物跑台上进行8周的大强度运动训练,每天训练30 min,每周6天,坡度为0,跑速每周递增,分别为15 m/min,22 m/min,27 m/min,31 m/min,35 m/min,38 m/min,40 m/min,42 m/min.白藜芦醇 运动组每天按50 mg/kg体质量的剂量灌喂白藜芦醇,其他两组灌喂同剂量的牛理盐水.末次训练结束后,禁食8 h,乙醚麻醉,股动脉取血,肝素抗凝,制备血浆.③实验评估:测定血浆中超氧化物歧化酶活性、谷胱甘肽过氧化物酶活性和丙二醛含量,三酰甘油、总胆固醇、高密度脂蛋白胆固醇,低密度脂蛋白胆固醇含量.结果:30只大鼠均进入结果分析.运动组、白藜芦醇 运动组大鼠血浆丙二醛、低密度脂蛋白胆固醇水平较运动组分别下降47.7%(P<0.01)和15.0%(P<0.05),血浆谷胱甘肽过氧化物酶、高密度脂蛋白胆固醇水平较运动组分别升高10.1%(P<0.05)和16.6%(P<0.05).结论:白藜芦醇对大强度运动所引起的抗氧化能力下降和脂质代谢紊乱有明显的改善作用.     

Biochemical analysis of hepatic lipid in alcoholic and diabetic and control subjects

Percutaneous needle biopsy specimens of liver were obtained from alcoholic, diabetic and control patients. Micro-methods of lipid separation and quantification were employed to determine the detailed nature of hepatic lipid. Triglyceride is the major accumulating liver lipid in both alcoholic and diabetic patients. Cholesteryl ester levels were raised in both alcoholic and diabetic patients but only diabetic patients had significantly increased free cholesterol and phospholipid levels. Determination of phospholipid/free cholesterol ratios revealed a significant decrease in alcoholic cirrhosis compared with controls. Fatty acid ester analysis of hepatic phospholipid and triglyceride revealed significant differences between alcoholic patients and controls but not between diabetic patients and controls. An increased ratio of non-essential/essential fatty acids was found in the patients with alcoholic liver disease whereas those of diabetic patients were similar to the controls.     

Beneficial effects of a soy-based dietary supplement on lipid levels and cardiovascular risk markers in type 2 diabetic subjects

OBJECTIVE: Consumption of soy protein has recently been shown to improve the blood lipid levels in nondiabetic subjects. The purpose of this study was to evaluate if a dietary supplement of soy protein, isoflavones, and cotyledon fiber (Abalon) affects cardiovascular risk markers, blood glucose, and insulin levels in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: Twenty type 2 diabetic subjects participated in a crossover trial. They were randomized to double-blind supplementation for 6 weeks with Abalon (soy protein [50 g/day] with high levels of isoflavones [minimum 165 mg/day] and cotyledon fiber [20 g/day]) or placebo (casein [50 g/day] and cellulose [20 g/day]), separated by a 3-week wash-out period. RESULTS: The results are expressed as means +/- SD. The percentage mean treatment difference between Abalon and placebo demonstrated significantly lower mean values after Abalon for LDL cholesterol (10 +/- 15%, P < 0.05), LDL/UHDL ratio (12 +/- 18%, P < 0.05), apolipoprotein (apo) B100 (30 +/- 38%, P < 0.01), triglycerides (22 +/- 10%, P < 0.05), and homocysteine (14 +/- 21%, P < 0.01), whereas the total cholesterol value tended to be less significant but still lower (8 +/- 15%, P < 0.08). No change occurred in HDL cholesterol, apo B100/apo A1 ratio, plasminogen activator inhibitor 1, factor VIIc, von Willebrand factor, fibrinogen, lipoprotein(a), glucose, HbA1c, or 24-h blood pressure. CONCLUSIONS: These results indicate beneficial effects of dietary supplementation with Abalon on cardiovascular risk markers in type 2 diabetic subjects. This improvement is seen even in individuals with near-normal lipid values.     

Serum lipid profile,oxidative status,and paraoxonase 1 activity in hyperemesis gravidarum

The aim of this study was to investigate lipid profile, paraoxonase 1 (PON1) activity, and oxidative stress status in the serum of hyperemesis gravidarum (HG) patients. Thirty‐six HG cases and 36 normal pregnants were included in the study. Serum total cholesterol (TC), triglyceride (TG), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), apoproteins A1 (apo A1) and B (apo B), malondialdehyde (MDA), and total antioxidant activity (TAO) values and PON1 and arylesterase activities were determined. Although serum TC, TG, LDL‐C, and apo B levels were not different among; the groups (P>0.05), HDL‐C (P=0.01) and apo A1 (P=0.007) levels were lower in HG patients than in normal pregnants. HG group had significantly lower serum PON1 (P=0.03) and arylesterase activities (P=0.03) compared with the control group. Additionally, mean TAO values were lower (P=0.01) and MDA levels were higher (P=0.02) in HG group than in the healthy pregnants. A significant negative correlation between PON1 and MDA was found in HG group (r=?0.33, P<0.05). The findings of this study have revealed that HG may be one of the conditions in which oxidant and antioxidant balance is impaired. J. Clin. Lab. Anal. 23:105–109, 2009. © 2009 Wiley‐Liss, Inc.