Lipid peroxidation in the lungs upon inhalation exposure to low concentrations of lead salts

Effects of inhalation with low concentration lead salts on lipid peroxidation intensity and antioxidative system state were investigated in respiratory pulmonary branch in rats after both short-term and chronic exposures to 0.01% Pb(CH3COO)2. It was shown that the short-term toxic action had considerably affected on the antioxidant system state in lungs as a result of tissue antioxidative activity exhausting. Under the chronic lead inhalation penetrating disorders in adaptive mechanisms were found. It was reflected in lipid peroxidation product accumulation and decreased parameters of antioxidant defense, and development of energy deficiency.     

Antioxidant defense of betaine against isoprenaline-induced myocardial infarction in rats

We investigated the antioxidant preventive effect of betaine on isoprenaline-induced myocardial infarction in male albino rats. Isoprenaline induced myocardial infarction was manifested by a moderate elevation in the levels of diagnostic marker enzymes (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and creatine phosphokinase) and homocysteine in plasma of experimental rats. Significant rise in the level of lipid peroxidation with a concomitant decline in the levels of myocardial non-enzymic (reduced glutathione) and enzymic antioxidants (glutathione peroxidase, glutathione-S-transferase, catalase and superoxide dismutase) was also observed. Oral pretreatment with betaine significantly prevented isoprenaline-induced alterations in the levels of diagnostic marker enzymes and homocysteine in plasma of experimental groups of rats. It counteracted the isoprenaline-induced lipid peroxidation and maintained the myocardial antioxidant defense system at near normal. Histopathological observations also confirmed the protective effect of betaine against isoprenaline-induced myocardial infarction. The results of the present investigation indicate that the protective effect of betaine is probably related to its ability to strengthen the myocardial membrane by its membrane stabilizing action or to a counteraction of free radicals by its antioxidant property.     

Age-related peculiarities of antioxidant system functioning in the blood of ostriches

The intensity of lipid peroxidation, activity of some enzymes antioxidant system - superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, amount of recovered glutathione and ceruloplasmin in the blood serum of ostriches in a period from 6- to 60-month age were first investigated. The increase of concentration of lipid peroxidation products is accompanied by the decline of amount of general lipids in the ostriches blood. Every life cycle period of ostriches is characterized by the indexes of functioning of the antioxidant system and intensity of accumulation intermediate lipid peroxidation products inherent in it. The pubescence period and intensive oviposition are characterized by the increase of products lipid peroxidation concentration and decrease of antioxidant enzymes activity, which can testify to the exhaustion of protective possibilities of enzymatic link of antioxidant defence.     

Cardioprotective effect of alpha-mangostin, a xanthone derivative from mangosteen on tissue defense system against isoproterenol-induced myocardial infarction in rats

Increased oxidative stress and antioxidant deficit have been suggested to play a major role in isoproterenol-induced myocardial infarction. The present study was designed to evaluate the effect of alpha-mangostin on the antioxidant defense system and lipid peroxidation against isoproterenol-induced myocardial infarction in rats. Induction of rats with ISO (150 mg/kg body weight, ip) for 2 days resulted in a marked elevation in lipid peroxidation, serum marker enzymes (LDH, CPK, GOT, and GPT) and a significant decrease in the activities of endogenous antioxidants (SOD, CAT, GPx, GST, and GSH). Pre-treatment with alpha-mangostin (200 mg/kg of body weight per day) orally for 6 days prior to the ISO administration and 2 days along with ISO administration significantly attenuated these changes when compared to the individual treatment groups. These findings indicate the protective effect of alpha-mangostin on lipid peroxidation and antioxidant tissue defense system during ISO-induced myocardial infarction in rats.     

Effect of quercetin on nicotine-induced biochemical changes and DNA damage in rat peripheral blood lymphocytes

We elucidated the protective effect of quercetin, a polyphenolic flavonoid, on lipid peroxidation, endogenous antioxidant status and DNA damage during nicotine-induced toxicity in cultured rat peripheral blood lymphocytes as compared to N-acetylcysteine (NAC), a well-known antioxidant. Lymphocytes were exposed to nicotine (3 mM) with and without quercetin and NAC (1 mM) in RPMI-1640 medium for 1 h. In preliminary experiments to fix the effective dose of quercetin, different doses of quercetin (25, 50, 75, 100 and 200 microM) were administered to lymphocytes with nicotine, and lipid peroxidation markers (thiobarbituric acid reactive substances and hydroperoxides) were analysed. A 75 microM dose of quercetin was found to be effective as evidenced by decreased lipid peroxidation. To evaluate the protective potential of quercetin against genotoxic effects of nicotine we used comet and micronucleus assays, which are valid parameters to assess genetic damage. In addition, biochemical changes including lipid peroxidation and antioxidant status were assessed. There were significant increases in the levels of lipid peroxidation, comet parameters and micronuclei frequencies, followed by decrease in the endogenous antioxidant status, in nicotine-treated lymphocytes, which were brought back to near normal by quercetin or NAC treatment. The protective effect of quercetin against nicotine toxicity was comparable to that of NAC. These findings suggest that quercetin can be as effective as NAC in protecting rat peripheral lymphocytes against nicotine-induced cellular and DNA damage.     

Antioxidant activity of extract from Polygonum cuspidatum

Numerous diseases are induced by free radicals via lipid peroxidation, protein peroxidation and DNA damage. It has been known that a variety of plant extracts have antioxidant activities to scavenge free radicals. Whether Polygonum cuspidatum Sieb. et Zuce has antioxidant activity is unknown. In this study, dried roots of Polygonum cuspidatum were extracted by ethanol and the extract was lyophilized. Free radical scavenging assays, superoxide radical scavenging assays, lipid peroxidation assays and hydroxyl radical-induced DNA strand scission assays were employed to study antioxidant activities. The results indicate that the IC50 value oí Polygonum cuspidatum extract is 110 microg/ml in free radical scavenging assays, 3.2 microg/ml in superoxide radical scavenging assays, and 8 microg/ml in lipid peroxidation assays, respectively. Furthermore, Polygonum cuspidatum extract has DNA protective effect in hydroxyl radical-induced DNA strand scission assays. The total phenolics and flavonoid content of extract is 641.1 +/- 42.6 mg/g and 62.3 +/- 6.0 mg/g. The results indicate that Polygonum cuspidatum extract clearly has antioxidant effects.     

Synergistic interactions of Ferulic acid with Ascorbic acid: Its cardioprotective role during isoproterenol induced myocardial infarction in rats

Studies on the lipid peroxidation and antioxidant changes and their significance during myocardial injury have provided a new insight into the pathogenesis of heart disease. The heart failure subsequent to myocardial infarction may be associated with an antioxidant deficit as well as increased myocardial oxidative stress. The present study was designed to evaluate the effect of the combination of ferulic acid and ascorbic acid on antioxidant defense system and lipid peroxidation against isoproterenol (ISO)-induced myocardial infarction in rats. Induction of rats with isoproterenol (150 mg/kg body weight daily, i.p.) for 2 days resulted in a marked elevation in lipid peroxidation, serum marker enzymes (LDH, CPK, GOT, and GPT), and a significant decrease in activities of endogenous antioxidants (SOD, GPx, GST, CAT, and GSH). Pre-co-treatment with the combination of ferulic acid (20 mg/kg body weight/day) and ascorbic acid (80 mg/kg body weight/day) orally for 6 days, significantly attenuated these changes when compared to the individual treatment groups. Histopathological observations were also in correlation with the biochemical parameters. Thus, ferulic acid and ascorbic acid significantly counteracted the pronounced oxidative stress effect of ISO by the inhibition of lipid peroxidation, restoration of antioxidant status, and myocardial marker enzymes levels. In conclusion, these findings indicate the synergistic protective effect of ferulic acid and ascorbic acid on lipid peroxidation and antioxidant defense system during ISO-induced myocardial infarction and associated oxidative stress in rats.     

Cholesterol-rich diets have different effects on lipid peroxidation, cholesterol oxides, and antioxidant enzymes in rats and rabbits

The objective of this study was to compare the effect of cholesterol feeding of rats and rabbits. The levels of lipid peroxidation products and oxysterols in the plasma of the two species plus the antioxidant enzyme activities in the liver and erythrocytes were measured to explain their different susceptibilities to atherosclerosis. Our study showed that rats are less susceptible than are rabbits to the atherogenic effect of a cholesterol-rich diet because of differences in lipid peroxidation products as well as antioxidant enzymes activities in their livers. In rabbits, cholesterol feeding produced severe hypercholesterolemia (43-fold increase) and increased plasma and liver lipid peroxidation. Total as well as the individual oxysterol contents of 7alpha-, 7beta-hydroxycholesterol, alpha-epoxy, beta-epoxycholesterol, cholestanetriol, 7-keto, and 27-hydroxycholesterol significantly increased in the plasma of hypercholesterolemic (HC) rabbits. Erythrocyte glutathione peroxidase (GSH-Px) activity significantly decreased whereas catalase activity significantly increased in HC rabbits. In rats cholesterol feeding increased the plasma cholesterol only twofold and had no effect on plasma or liver lipid peroxidation. Only 7alpha- and 7beta-hydroxycholesterol increased and no change was observed in any of the antioxidant enzymes activity in the erythrocytes. Although cholesterol feeding caused a 10-fold increase of liver cholesterol as ester in both rats and rabbits, the antioxidant enzyme GSH-Px and catalase activities in the liver significantly increased in rats but significantly decreased in rabbits. The increase of GSH-Px and catalase activities in the liver of cholesterol fed rats could have a protective role against oxidation, thus preventing the formation of lipid peroxidation and oxysterols.     

Effect of quercetin on nicotine-induced biochemical changes and DNA damage in rat peripheral blood lymphocytes

Abstract

We elucidated the protective effect of quercetin, a polyphenolic flavonoid, on lipid peroxidation, endogenous antioxidant status and DNA damage during nicotine-induced toxicity in cultured rat peripheral blood lymphocytes as compared to N-acetylcysteine (NAC), a well-known antioxidant. Lymphocytes were exposed to nicotine (3 mM) with and without quercetin and NAC (1 mM) in RPMI-1640 medium for 1 h. In preliminary experiments to fix the effective dose of quercetin, different doses of quercetin (25, 50, 75, 100 and 200 μM) were administered to lymphocytes with nicotine, and lipid peroxidation markers (thiobarbituric acid reactive substances and hydroperoxides) were analysed. A 75 μM dose of quercetin was found to be effective as evidenced by decreased lipid peroxidation. To evaluate the protective potential of quercetin against genotoxic effects of nicotine we used comet and micronucleus assays, which are valid parameters to assess genetic damage. In addition, biochemical changes including lipid peroxidation and antioxidant status were assessed. There were significant increases in the levels of lipid peroxidation, comet parameters and micronuclei frequencies, followed by decrease in the endogenous antioxidant status, in nicotine-treated lymphocytes, which were brought back to near normal by quercetin or NAC treatment. The protective effect of quercetin against nicotine toxicity was comparable to that of NAC. These findings suggest that quercetin can be as effective as NAC in protecting rat peripheral lymphocytes against nicotine-induced cellular and DNA damage.     

The Effects of Boron on Arsenic‐Induced Lipid Peroxidation and Antioxidant Status in Male and Female Rats

The aim of the present study was to investigate the possible protective effects of boron, an antioxidant agent, against arsenic‐induced oxidative stress in male and female rats. In total, 42 Wistar albino male and female rats were divided into three equal groups: The animals in the control group were given normal drinking water, the second group was given drinking water with 100 mg/L arsenic, and the third group was orally administered drinking water with 100 mg/kg boron together with arsenic. At the end of the 28‐day experiment, arsenic increased lipid peroxidation and damage in the tissues of rats. However, boron treatment reversed this arsenic‐induced lipid peroxidation and activities of antioxidant enzymes in rats. Moreover, boron exhibited a protective action against arsenic‐induced histopathological changes in the tissues of rats. In conclusion, boron was found to be effective in protecting rats against arsenic‐induced lipid peroxidation by enhancing antioxidant defense mechanisms.     

Antioxidant activity of extract from Polygonum aviculare L

Free radicals induce numerous diseases by lipid peroxidation, protein peroxidation, and DNA damage. It has been reported that numerous plant extracts have antioxidant activities to scavenge free radicals. Whether Polygonum aviculare L. (Polygonaceae) has antioxidant activity is unknown. In this study, dried Polygonum aviculare L. was extracted by ethanol, and the extract was lyophilized. The antioxidant activities of extract powder were examined by free radical scavenging assays, superoxide radical scavenging assays, lipid peroxidation assays and hydroxyl radical-induced DNA strand scission assays. The results show that the IC50 value of Polygonum aviculare L. extract is 50 microg/ml in free radical scavenging assays, 0.8 microg/ml in superoxide radical scavenging assays, and 15 microg/ml in lipid peroxidation assays, respectively. Furthermore, Polygonum aviculare L. extract has DNA protective effect in hydroxyl radical-induced DNA strand scission assays. The total phenolics and flavonoid content of extract is 677.4 +/- 62.7 microg/g and 112.7 +/- 13 microg/g. The results indicate that Polygonum aviculare L. extract clearly has antioxidant effects.     

Curcumin ameliorates oxidative stress during nicotine-induced lung toxicity in Wistar rats

Nicotine, a major toxic component of cigarette smoke has been identified as a major risk factor for lung related diseases. In the present study, we evaluated the protective effects of curcumin on lipid peroxidation and antioxidants status in bronchoalveolar lavage fluid (BALF) and bronchoalveolar lavage (BAL) of nicotine treated Wistar rats. Lung toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg body weight (5 days a week, for 22 weeks) and curcumin (80 mg/kg body weight) was given simultaneously by intragastric intubation for 22 weeks. Measurement of biochemical marker enzymes: alkaline phosphatase, lactate dehydrogenase, lipid peroxidation and antioxidants were used to monitor the antiperoxidative effects of curcumin. The increased biochemical marker enzymes as well as lipid peroxides in BALF and BAL of nicotine treated rats was accompanied by a significant decrease in the levels of glutathione, glutathione peroxidase, superoxide dismutase and catalase. Administration of curcumin significantly lowered the biochemical marker enzymes, lipid peroxidation and enhanced the antioxidant status. The results of the present study suggest that curcumin exert its protective effect against nicotine-induced lung toxicity by modulating the biochemical marker enzymes, lipid peroxidation and augmenting antioxidant defense system.     

Iron and exercise induced alterations in antioxidant status. Protection by dietary milk proteins

Lipid peroxidation stress induced by iron supplementation can contribute to the induction of gut lesions. Intensive sports lead to ischemia reperfusion, which increases free radical production. Athletes frequently use heavy iron supplementation, whose effects are unknown. On the other hand, milk proteins have in vitro antioxidant properties, which could counteract these potential side effects. The main aims of the study were: (1) to demonstrate the effects of combined exercise training (ET) and iron overload on antioxidant status; (2) to assess the protective properties of casein in vivo; (3) to study the mechanisms involved in an in vitro model.

Antioxidant status was assessed by measuring the activity of antioxidant enzymes (superoxide dismutase (SOD); glutathione peroxidase (GSH-Px)), and on the onset of aberrant crypts (AC) in colon, which can be induced by lipid peroxidation. At day 30, all ET animals showed an increase in the activity of antioxidant enzymes, in iron concentration in colon mucosa and liver and in the number of AC compared to untrained rats. It was found that Casein's milk protein supplementation significantly reduced these parameters. Additional information on protective effect of casein was provided by measuring the extent of TBARS formation during iron/ascorbate-induced oxidation of liposomes. Free casein and casein bound to iron were found to significantly reduce iron-induced lipid peroxidation. The results of the overall study suggest that Iron supplementation during intensive sport training would decrease anti-oxidant status. Dietary milk protein supplementation could at least partly prevent occurrence of deleterious effects to tissue induced by iron overload.     

Thiol antidotes effect on lipid peroxidation in mercury-poisoned rats

The effect of thiol antidotes 2,3-dimercapto-1-propanesulfonic acid (DMPS) and D-penicillamine (PA) on lipid peroxidation and on activities of some protecting enzymes in blood, liver and kidneys of mercury-poisoned rats has been studied. It has been found that Hg-poisoning is associated with increased lipid peroxidation in the liver and in the kidneys and with inactivation of superoxide dismutase (SOD) and catalase. Inhibition of SOD is caused by thiols treatment too, but in this case acceleration of lipid peroxidation has not been observed. Evidence is presented that in the liver, protection against mercury-induced lipid peroxidation is afforded by both thiols, while in the kidneys only PA has protective effect. In in vitro experiments it has been demonstrated that both antidotes can act as O2- scavengers and lipid peroxidation inhibitors, but PA is significantly more effective. On the basis of the obtained results a conclusion is drawn that in addition to the metal-removing ability, the antioxidant properties of the chelating agents may play an important role in manifestation of their beneficial effect in metal intoxications.     

Antioxidant properties of rimantadine in influenza virus infected mice and in some model systems

Influenza virus infection is associated with development of oxidative stress in lung and blood plasma, viz. increase of primary and secondary lipid peroxidation products. It was established that rimantadine treatment led to a decrease of the products of lipid peroxidation in tissues of mice experimentally infected with influenza virus A/Aichi/2/68 (H3N2). The effect is strongest in blood plasma (a decrease of about 50%) and weaker in the lung (about 20%). To elucidate the mechanism of this action of rimantadine, experiments were carried out with some model systems. The capability of rimantadine to scavenge superoxide radicals (scavenging properties) was studied in a system of xanthine-xanthine oxidase to generate superoxide. The amount of superoxide was measured spectrophotometrically by the NBT-test and chemiluminesce. Rimantadine does not show scavenging properties and its antioxidant effect observed in vivo, is not a result of its direct action on the processes of lipid peroxidation and/or interaction with antioxidant enzymes. The antioxidant properties of rimantadine were investigated by measurement of induced lipid peroxidation in a Fe2+ and (Fe2+ - EDTA) system with an egg liposomal suspension. Our findings with model systems do not prove an antioxidant or prooxidant effect of the drug on the processes of lipid peroxidation. Apparently, the observed antioxidant effect of rimantadine in vivo is not connected directly with free radical processes in the organism.     

Antioxidant effect of dipyridamole (DIP) and its derivative RA 25 upon lipid peroxidation and hemolysis in red blood cells

The antioxidant effects of dipyridamol (DIP), a coronary vasodilator, and its derivative RA-25 were compared in intact red blood cells (RBC) and in isolated ghost membranes. Both compounds are quite effective antioxidants in cumene hydroperoxide-induced lipid peroxidation of RBC, showing a much smaller effect for hydrogen peroxide oxidation. The antioxidant effect of DIP was considerably higher than that of RA25. For isolated ghost membranes, the apparent IC50 (the drug concentration that produces 50% inhibition of lipid peroxidation) in cumene hydroperoxide-induced peroxidation was 25 microM, while the maximum protective effect of RA-25 was around 30% in the drug concentration range of 50-100 microM. The drugs can protect the oxidative hemolysis induced by cumene hydroperoxide with a lower effect when the hemolysis is induced by H2O2. The significant antioxidant effect against damages induced by cumene hydroperoxide suggests that DIP, due to its lipophilic character, can interact with RBC membranes, and the protective effect is associated with the binding of the drug to the membrane. On the other hand, RA-25 is more hydrophilic than DIP, binds to the membrane to a smaller extent, and, for this reason, has a lower antioxidant effect.     

Effects of ethanol and limontar in the antenatal period of development on lipid peroxidation process and antioxidant defense system in the brain and liver tissue of fetal and newborn rats]

The process of lipid peroxidation and the system of antioxidant defense in brain and liver of fetuses on the 20th day of gestation and 1 day old rats after antenatal exposure to ethanol and limontar were studied. It was shown that antenatal exposure to ethanol led to activation of the process of lipid peroxidation in brain and to inhibition of of the enzyme system of antioxidant defense in liver of fetal and newborn rats. Limontar promoted the normalization of both the process of lipid peroxidation and the system of antioxidant defense.     

Phenolic chain-breaking antioxidants--their activity and mechanisms of action

This tutorial review is focused on some mechanistic aspects of peroxidation process and chemistry of phenolic chain-breaking antioxidants. Lipids are susceptible to oxidative degradation caused by radicals and during autoxidation (peroxidation) the chain reaction is mediated by peroxyl radicals leading to damage of integrity and the protective and organizational properties of biomembranes. Phenolic antioxidants provide active system of defence against lipid peroxidation, however, the effectiveness of their antioxidant action depends on several important parameters. Stoichiometry of the reaction with free radicals, fate of a phenoxyl radical, polarity of the microenvironment, localization of antioxidant molecules, their concentration and mobility, kinetic solvent effects, and interactions with other co-antioxidants are considered. Principal mechanisms of reaction between phenols and free radicals (Hydrogen Atom Transfer, Proton Coupled Electron Transfer and two mechanisms based on separate electron transfer and proton transfer steps) are described.     

Anomalous antioxidant effects in selenium- and vitamin E-deficient liver mitochondria

In this study, we investigate the mechanisms of two anomalous protective effects of exogenous vitamin E that had previously been postulated to involve either a specific antioxidant effect or a non-antioxidant function of the vitamin. These atypical vitamin E effects were observed during the prevention of NAD-induced respiratory decline occurring in homogenates and mitochondria prepared from vitamin E- and selenium-deficient rat liver. The study showed neither hypothesis to be true; rather, the two effects, one in homogenates and the other in isolated mitochondria, were explained by other mechanisms. The protective effect against respiratory decline in homogenates was found to result from interference in the thiobarbituric acid assay for lipid peroxidation by ethanol (the conventional solvent for vitamin E addition). With other non-interfering solvents, inhibition of lipid peroxidation by vitamin E, in contrast to previous studies, correlated perfectly with prevention of respiratory decline. The atypical vitamin E effect occurring in isolated mitochondria—and consisting of a requirement for cytosol proteins for the prevention of respiratory decline by exogenous vitamin E—was found to be caused by the prevention of adverse glass effects and not by the action of vitamin E-specific binding proteins. Frequent failures in the combined protective effect of vitamin E and cytosol, which had been a major complication of respiratory decline studies, were found to be caused by phospholipase activity generated during isolation procedures. Irreversible deactivation of respiratory enzymes by lipid peroxidation was found not to be involved in the respiratory decline mechanism. In memoriam: Klaus Schwarz, MD, 1914–1978.