Prevention of hepatocyte injury and lipid peroxidation by iron chelators and alpha-tocopherol in isolated iron-loaded rat hepatocytes

These experiments were performed to characterize the relationship between lipid peroxidation and hepatocyte viability in iron overload. Hepatocytes were isolated from rats with chronic dietary iron overload and the effects of in vitro iron chelation on lipid peroxidation, cell viability and ultrastructure were studied over a 4-hr incubation period. Cell viability was significantly reduced at 3 and 4 hr in iron-loaded hepatocytes compared with controls and was preceded by an increase in iron-dependent lipid peroxidation. Similarly, extensive degenerative ultrastructural changes were observed in iron-loaded hepatocytes compared with controls after 4 hr of incubation. In vitro iron chelation with either deferoxamine or apotransferrin protected against lipid peroxidation, loss of viability and ultrastructural damage in iron-loaded hepatocytes. The addition of an antioxidant, alpha-tocopherol, also protected against lipid peroxidation and preserved cell viability over a 4-hr incubation. The protective effects of iron chelators and alpha-tocopherol support a strong association between iron-dependent lipid peroxidation and hepatocellular injury in iron overload.     

Lipid peroxidation and antioxidant enzymatic defense in patients with newly detected insulin-dependent diabetes mellitus]

Studies of lipid peroxidation and antioxidant enzymic defense in red cell membranes in 23 patients with newly detected insulin-dependent diabetes mellitus have revealed a statistically significant (2-fold) elevation of malonic dialdehyde lipid peroxidation products and a trend to a rise in the levels of lipid peroxides. This is parallelled by a certain overstrain of the cellular antioxidant defense system. The authors discuss the usefulness of administering antioxidant therapy at the onset of the disease in order to prevent the toxic injury of beta-cells and vascular endothelium cells by lipid peroxidation products.     

Effect of chronic smoking on lipid peroxidation and antioxidant status in gastric carcinoma patients

Oxidative stress plays an important role in malignant transformation and is postulated to be associated with increased lipid peroxidation. We determined the effects of chronic cigarette smoking on lipid peroxidation and antioxidant status in 100 male patients with gastric cancer and an equal number of age-matched healthy control subjects. The mean (SD) level of thiobarbituric acid reactive substances (TBARS) was higher in plasma (healthy non-smokers 3.1 [0.2]; healthy smokers 4.6 [0.2]; gastric cancer non-smokers 6.5 [1.0]; gastric cancer smokers 8.9 [3.1]) and erythrocytes (3.3 [0.6]; 4.6 [0.1]; 8.3 [0.9]; 13.2 [5.1]) from gastric cancer patients when compared with control subjects. TBARS level was higher in smokers than non-smoking gastric cancer patients. The activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-treansferase, reduced glutathione, and vitamins A, E and C were decreased in gastric cancer patients who were smokers as compared to other groups (p<0.001). Thus, there occurs lipid peroxidation and possible breakdown of antioxidant status in cigarette smoking, which may increase the risk of gastric cancer.     

Antioxidant and immunomodulatory effects of Viusid in patients with chronic hepatitis C

AIM:To investigate the efficacy of Viusid,a nutritional supplement,as an antioxidant and an immunomodulator in patients with chronic hepatitis C.METHODS:Sixty patients with chronic hepatitis C who were non-responders to standard antiviral treatment were randomly assigned to receive Viusid(3 sachets daily,n=30) or placebo(n=30) for 24 wk.The primary outcome was the change in serum malondialdehyde and 4-hydroxyalkenals(lipid peroxidation products).Secondary outcomes were changes in serum tumor necrosis factor...     

Ursodeoxycholic Acid Suppresses Extent of Lipid Peroxidation in Diseased Liver in Experimental Cholestatic Liver Disease

The therapeutic benefit of ursodeoxycholic acid (UDCA) in treating cholestatic liver disease is globally recognized. It is generally accepted that the mechanism of action of UDCA can be attributed to several diverse processes that appear to be uniformly targeted towards minimizing the deleterious actions of accumulated hydrophobic bile acids in the cholestatic liver. Since hydrophobic bile acids are prooxidants, emerging in vitro evidence suggests that UDCA may have an antioxidant mechanism of action. We hypothesize that UDCA suppresses the extent of lipid peroxidation in the cholestatic liver. This hypothesis was tested by assessing the extent of lipid peroxidation in livers harvested from chronic bile duct ligated (CBDL) rats dosed daily for 24 days with 5, 10, or 15 mg/kg UDCA. The extent of lipid peroxidation was evaluated by determining the hepatic content of conjugated dienes, lipid peroxides, and malondialdehyde. The data were compared with identical data collected from unoperated control and 24-day bile duct manipulated (SO) rats. In the two groups of control rats, UDCA has no effect on the serum indices of liver function. In CBDL rats, UDCA suppressed the increased extent of lipid peroxidation in the liver in a dose-dependent manner in the absence of improvement of laboratory parameters of liver function and hepatic architecture. In conclusion, UDCA suppresses the augmented extent of lipid peroxidation in the diseased liver of CBDL rats.     

Resistance of erythrocytes to lipid peroxidation in alcoholic patients.

The ability of erythrocytes to resist lipid peroxidation may be a useful marker of antioxidant status in alcoholic patients, in whom depletion of dietary antioxidants may combine with increased production of free radicals to produce liver damage. There are conflicting reports, however, on the resistance of erythrocytes from alcoholic patients to lipid peroxidation. This study examined the relation between the degree of alcohol induced liver disease and the resistance of erythrocytes to chemically induced lipid peroxidation, measuring lipid peroxidation as malondialdehyde production. Erythrocytes from alcoholic patients with Child's C cirrhosis had significantly increased resistance to lipid peroxidation compared with both controls (p < 0.001) and alcoholic patients with moderate liver disease (p < 0.001). There was no difference between alcoholic patients with moderate liver disease and controls. Increased resistance to free radical initiated lipid peroxidation in alcoholic patients is related to liver damage rather than to alcohol abuse alone. This could arise from changes in the lipid composition of the erythrocyte membranes resulting from abnormal liver function. Tests of antioxidant status based upon the resistance of erythrocytes to free radical stress in vitro may therefore be flawed when such changes in membrane lipid composition can occur.     

Biomarkers of lipid peroxidation, airway inflammation and asthma.

Oxidative stress, specifically lipid peroxidation, is believed to contribute to the pathophysiology of asthma. This review highlights the pathways through which reactive oxygen species (ROS) may lead to lipid peroxidation. The potential of both the innate and acquired immune systems to activate inflammatory cells and release ROS that may overwhelm the host antioxidant defences and cause lipid peroxidation, accompanied by detrimental pathophysiological effects, are discussed. Despite the evidence demonstrating the importance of lipid peroxidation, systematic characterisation of oxidative stress and antioxidant defences has not been undertaken, largely due to the lack of appropriate biomarkers. This review discusses the emergence of isoprostanes (specifically 8-iso-prostaglandin F2alpha) as reliable, in vivo markers of lipid peroxidation, which provides an appropriate tool for studying oxidative stress. Furthermore, the development of techniques to study induced sputum and breath condensate, derived directly from the airway surface, enables the site of oxidative damage to be closely assessed. Evidence suggests that dietary changes that have occurred over recent years have increased susceptibility to lipid peroxidation, due to reduced antioxidant defences. To date, the limited number of long-term (>1 week) supplementation trials have been promising. However, the development of techniques to study isoprostanes in airway-lining fluid pave the way for further studies investigating the potential for antioxidant supplements to be used as routine therapy in asthma.     

Effect of therapy with antibiotics on lipid metabolism and antioxidant reserve of patients with ischemic heart disease during Chlamydia pneumoniae infection

Effect of therapy with azithromycin and doxycycline on lipid metabolism, processes of lipid peroxidation and state of antioxidant defense was studied in patients with ischemic heart disease with elevated titer of antibodies to Chlamydia Pneumonia. Therapy with azithromycin (500 mg/day for 2 months) was associated with lowering of antibody titer, moderate improvement of lipid spectrum, marked decrease of activity of lipid peroxidation and augmentation of blood plasma antioxidant reserve. There were no such changes in a group of doxycycline treated patients. This difference can be attributed to more pronounced antimicrobial activity of azithromycin against Chlamydophila Pneumonia and its intrinsic antioxidant properties.     

Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein

BACKGROUND & AIMS: The mechanisms of liver injury in chronic hepatitis C virus (HCV) infection are poorly understood. Indirect evidence suggests that oxidative stress and mitochondrial injury play a role. The aim of this study was to determine if the HCV core protein itself alters mitochondrial function and contributes to oxidative stress. METHODS: HCV core protein was expressed in 3 different cell lines, and reactive oxygen species (ROS) and lipid peroxidation products were measured. RESULTS: Core expression uniformly increased ROS. In 2 inducible expression systems, core protein also increased lipid peroxidation products and induced antioxidant gene expression as well. A mitochondrial electron transport inhibitor prevented the core-induced increase in ROS. A fraction of the expressed core protein localized to the mitochondria and was associated with redistribution of cytochrome c from mitochondrial to cytosolic fractions. Sensitivity to oxidative stress was also seen in HCV transgenic mice in which increased intrahepatic lipid peroxidation products occurred in response to carbon tetrachloride. CONCLUSIONS: Oxidative injury occurs as a direct result of HCV core protein expression both in vitro and in vivo and may involve a direct effect of core protein on mitochondria. These results provide new insight into the pathogenesis of hepatitis C and provide an experimental rationale for investigation of antioxidant therapy.     

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.     

Hypoglycemic effect of Costus pictus D. Don on alloxan induced type 2 diabetes mellitus in albino rats

ObjectiveTo demonstrate the effect of aqueous extract of Costus pictus (C. pictus) leaves on blood glucose, lipid profile and liver antioxidant enzymes and lipid peroxidation in alloxan induced diabetic rats.MethodsAqueous extract of C. pictus (AECP) leaves was administered orally for 30 days and its effect on blood glucose, lipid profile, hepatic marker enzymes such as serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum urea, creatinine, protein and albumin content and liver antioxidant enzymes such as catalase, peroxidase, superoxide dismutase and lipid peroxidation in alloxan induced diabetic rats were examined.ResultsOral administration of aqueous extract of C. pictus leaves to diabetic rats for 30 days significantly reduced the levels of blood glucose, lipid profile, lipid peroxidation, liver marker enzymes, urea, creatinine and increased the levels of antioxidant enzymes.ConclusionsThe aqueous extract of C. pictus leaves controls the blood glucose level, improves lipid metabolism and prevents diabetic complications associated with lipid peroxidation and also maintains the antioxidant enzymes in experimental diabetic rats. Therefore, it can be recommeded for the prevention of diabetes mellitus.     

慢性愤怒应激对衰老大鼠学习记忆能力的影响及其脂质过氧化机制

目的 观察慢性愤怒应激对D-半乳糖(D-gal)引起的衰老大鼠空间学习记忆能力的影响,并从脂质过氧化与抗氧化角度解释其作用机制.方法 采用夹尾间接激怒法诱导被攻击大鼠产生愤怒应激,观察慢性愤怒应激对衰老大鼠空间学习记忆能力和血清SOD活性及心、肝组织MDA、LPF含量的影响,分析心、肝MDA、LPF含量与血清SOD活性的相关性.结果 愤怒D-gal组大鼠较D-gal组寻台时间显著延长(P＜0.05),血清SOD活性显著降低(P＜0.05),心、肝组织MDA、LPF含量显著提高(P＜0.05,P＜0.01),心、肝MDA、LPF含量与血清SOD活性呈负相关.结论 慢性愤怒应激可降低衰老大鼠的学习记忆能力,加速衰老进程.抑制机体抗氧化能力,加重心、肝等重要脏器组织脂质过氧化可能是其机制之一.     

Antioxidant treatment of pulmonary tuberculosis in patients with chronic alcoholism]

Study of the state of the antioxidant system (AOS) and lipid peroxidation (LPO), according to the data on the alpha-tocopherol content, diene conjugates and acid erythrocyte hemolysis in 69 patients suffering from pulmonary tuberculosis concurrent with chronic alcoholism, has revealed significant differences as against the findings related to healthy subjects (36), to those with stage 11 alcoholism (31) and pulmonary tuberculosis patients (51). Favourable changes in the AOS and LPO during complex treatment that includes antioxidant agents were less manifested in patients with combined pathology and appeared at later terms than in tuberculosis patients. The antioxidant therapy of tuberculosis in chronic alcoholics should take a prolonged time, at least 4 months, since the first favourable changes in the AOS and LPO parameters appear after 4 months, while normalization does not set in even after 6 months.     

Evidence of a systemic phenomenon for oxidative stress in cholestatic liver disease

BACKGROUND: There is considerable evidence indicating that the severity of hepatic damage in individuals with cholestatic liver disease is causally associated with the extent of intrahepatic oxidative stress. Increased levels or accelerated generation of reactive oxygen species and toxic degradative products of lipid peroxidation have been reported in the plasma of individuals with chronic liver disease and animal models of liver disease. Hence, by virtue of their increased presence in the circulation, it is not unreasonable to suppose that they may account for extrahepatic tissue damage in chronic liver disease. MATERIALS AND METHODS: This hypothesis was tested by determining plasma levels of the ubiquitous antioxidant glutathione (GSH) and lipid peroxides (LP), together with assessment of the extent of lipid peroxidation in the kidney, brain, and heart, in 24 day chronically bile duct ligated (CBDL) rats. The extent of lipid peroxidation in tissues was based on measurement of conjugated dienes, lipid peroxides, and malondialdehyde (MDA) content. Data were compared with identical data collected from unoperated control, pair fed, 24 day bile duct manipulated (sham operated), and pair fed sham operated rats. RESULTS: In CBDL rats, total and reduced plasma GSH levels were almost half those determined in all control rats. Plasma, kidney, and heart LP levels were significantly increased in CBDL rats compared with controls. MDA levels were significantly higher in the kidney, brain, and heart homogenates prepared from CBDL rats compared with MDA content measured in tissue homogenates prepared from the four groups of control rats. CONCLUSIONS: Our data show that experimental cholestatic liver disease is associated with increased lipid peroxidation in the kidney, brain, and heart. Hence we have concluded that the oxidative stress in cholestatic liver disease is a systemic phenomenon probably encompassing all tissues and organs, even those separated by the blood-brain barrier.     

Oxidative stress and potential interventions to reduce oxidative stress in overweight and obesity

PURPOSE: Obesity may be a state of chronic oxidative stress. Oxidative stress may be the mechanism underlying the development of co-morbidities in obesity. This review provides a summary of the available evidence regarding systemic oxidative stress in young, older and clinical obese populations. METHODS: Medline was searched for all available articles published between 1975 and 2006 that evaluated oxidative stress biomarkers in resting conditions or following various interventions in overweight and obese humans. RESULTS: Obesity elevates oxidative stress in young, old and clinical populations as shown by elevations in lipid peroxidation (malondialdehyde, hydroperoxides, 4-hydroxynonenal, isoprostanes, conjugated dienes) or protein oxidation (8-hydroxy-deoxyguanosine). Lipid peroxidation is associated with several indices of adiposity and a low systemic antioxidant defence (i.e. antioxidant enzymes, tissue dietary antioxidants, glutathione). Oxidative stress may be exacerbated with acute exercise, advancing age or co-existing clinical conditions and may be corrected by improving antioxidant defences through fat volume reduction via surgery, pharmacological agents, exercise and/or dietary modification. CONCLUSION: Oxidative stress is related to chronic disease in obesity, but is reversible with one or more interventions described above.     

Effect of PON1 polymorphism on HDL antioxidant potential is blunted with aging

Paraoxonase1 is a HDL-associated enzyme, which is responsible for their antioxidant property. This study was aimed to investigate the effect of PON1 [Q192R] and [L55M] genotypes on susceptibility of LDL and HDL to lipid peroxidation and on antioxidant activity of HDL as a function of aging. Seventy-eight healthy subjects distributed in two age groups, young (20-30 years) and elderly (60-89 years) were recruited. PON1 activities and genotype polymorphisms were determined for each subject. LDL and HDL susceptibility to lipid peroxidation was evaluated by the measure of lag-phase (LP) for conjugated diene formation. HDL antioxidant property was evaluated by the measure of their capacity to protect LDL against lipid peroxidation. Our results show that LP for LDL and HDL peroxidation decreased with age of donors. Moreover, PON1 genotypes affect significantly the susceptibility of LDL and HDL to lipid peroxidation. Furthermore, basal- and salt-stimulated paraoxonase as well arylesterase activities were significantly reduced in elderly compared to young subjects. These results show a beneficial effect of PON1 towards susceptibility of HDL to oxidation as well to their antioxidant effect. However, this PON1 protective effect seems to be blunted with advancing age. Altogether our results suggest that the decrease in the PON1 protective effect with aging may contribute to the acceleration of the atherosclerosis process in elderly.     

Antioxidants, lipid peroxidation and lipoproteins in primary hypertension

The antioxidants and lipid peroxidation products are being extensively studied because of their potential importance and pathogenetic role in several non-communicable diseases like cardiovascular diseases and cancer, but the data on hypertension is scanty. Therefore, the present study aimed to assess the levels of lipid peroxidation and antioxidants besides dislipidemia changes among 32 newly diagnosed male hypertensives by comparing them with an equal sample of normotensives. Significant increase in serum lipid peroxide levels and decrease in antioxidant enzyme superoxide dismutase and vitamins E and A were observed among hypertensives than the controls. Hypertensives had higher total cholesterol, low-density lipoprotein cholesterol, triglycerides, body mass index and low high-density lipoprotein cholesterol levels than normotensives. The percentage prevalence of hypercholesterolemia, hypertriglyceridemia, low high-density lipoprotein cholesterol and obesity was higher in study subjects. Obese hypertensives had significantly higher levels of lipid peroxides and lipids with no change in antioxidant status than normal-weight hypertensives. Our results suggest that hypertensive patients may have elevated lipid peroxidation, lipids and reduced protection from antioxidants, which may contribute to the propensity in such patients to develop cardiovascular diseases, and to correct this, antioxidant supplementation besides weight reduction may be helpful to reduce the severity of burden.     

Exercise-induced quadriceps oxidative stress and peripheral muscle dysfunction in patients with chronic obstructive pulmonary disease

Exercise-induced muscle oxidative stress may be involved in the myopathy associated with chronic obstructive pulmonary disease (COPD). This study was designed to look at whether local exercise induces muscle oxidative stress and whether this oxidative stress may be associated with the reduced muscle endurance in patients with COPD. Quadriceps endurance was measured in 12 patients with COPD (FEV1 = 0.96 +/- 0.14 SEM) and 10 healthy sedentary subjects by repeated knee extensions of the dominant leg. Biopsies of the vastus lateralis muscle were obtained before and 48 hours after exercise. Muscle oxidative stress was measured by lipid peroxidation and oxidized proteins. Muscle antioxidant was evaluated by peroxidase glutathion activity. Quadriceps endurance was significantly reduced in patients with COPD when compared with the healthy control subjects (p < 0.01). Forty-eight hours postexercise, only patients with COPD had a significant increase in muscle lipid peroxidation (p < 0.05) and oxidized proteins (p < 0.05), whereas increased peroxidase glutathion activity was only observed in control subjects (p < 0.05). Both increases in muscle lipid peroxidation and oxidized proteins were significantly and inversely correlated with quadriceps endurance capacity in COPD (p < 0.05). In summary, local exercise induced muscle oxidative stress in patients with COPD, whereas it failed to raise antioxidant activity. In these individuals, muscle oxidative stress was associated with a reduced quadriceps endurance.     

Features of lipid peroxidation in patients with diabetes mellitus before and after therapy by a method of transplantation of human fetal islet cell cultures

The authors discussed the results of changes in the intensity of lipid peroxidation and antioxidant activity in 70 patients with type I diabetes mellitus (severe forms) before and in 32 patients after the transplantation of human fetal pancreatic islet cell cultures. Lipid peroxidation, antioxidant activity, indices of glycolysis and carbohydrate metabolism were investigated. In some cases metabolic derangement was noted against a background of a decrease in the end products of lipid peroxidation but in a majority of diabetic patients an increase in LPO intensity was noted against a background of raised antioxidant activity, high activity of glycolytic reactions and inhibition of Krebs' cycle. The greatest effect of transplantation was noted in a group of patients who had demonstrated high levels of lactate and the lactate-pyruvate ratio before transplantation. Therefore LPO indices can serve as a criterion of the selection of patients with insulin dependent diabetes mellitus for pancreatic endocrine tissue transplantation.     

Effect of hemodialysis on lipid peroxidation and antioxidant system in patients with chronic renal failure.

Plasma lipid peroxidation, activity of erythrocyte superoxide dismutase (SOD) and catalase, and serum antioxidant activity (AOA) in uremic patients were examined before and after hemodialysis. An increased level of lipid peroxidation, a decreased serum AOA level, and elevated SOD and normal catalase activity before hemodialysis were observed in uremic patients compared with controls. Hemodialysis was found to produce increased lipid peroxidation, a simultaneous decrease of SOD activity, and lack of any changes in serum AOA and erythrocyte catalase. It is suggested that intensification of lipid peroxidation during hemodialysis could account for accelerated progress of atherosclerosis in patients with renal insufficiency.