Lipid peroxidation during extreme hyperthermia of rats

The influence of extremal cryoeffects on the state of prooxidant and antioxidant systems in the blood serum and heart tissues was studied in young and old rats. It is shown that kinematic parameters of chemiluminescence after cold effects are less expressed in the blood serum of old animals than in young ones. The level of TBA-active products in the blood of young rats was lower than in old ones. After the 6th and 9th cold effect the content of TBA-active products in old animal appoaches such indices in young animals. Three weeks after the cold effects the content of TBA-active products in the myocardium of old rats corresponded to control indices, while in the young ones they were considerably lower. The fermentative link state was investigated in the antioxidant protection system. After the extremal cryoeffects glutathione reductase and glutathione peroxidase activity in old animals approaches its indices in intact rats, while catalase activity increases. Three weeks after cryoeffects one can observe a stable increase of fermentative activity of heart tissues both in old and young animals compared with the control that can evidence for the increase of the organism cold resistance.     

Effect of chronic ethanol treatment on the t-butyl hydroperoxide-dependent lipid peroxidation in rat liver

1. The effect of chronic ethanol consumption on the level of the t-butyl hydroperoxide (Bu'OOH)-induced lipid peroxidation in rat liver homogenate and subcellular fractions was measured using chemiluminescence technique and malondialdehyde formation. 2. It was shown that under the action of ethanol the rate of lipid peroxidation was decreased in the whole and "postnuclear" liver homogenates. 3. Ethanol significantly decreased the intensity of lipid peroxidation in microsomes, but did not affect the Bu'OOH-dependent process in mitochondria. 4. The level of lipid peroxidation was reduced after incubation of the total particulate fraction (mitochondria plus microsomes) with the undialysed cytosol from ethanol-treated rat liver. Dialysis of the cytosol prevented depressive effect of ethanol treatment on lipid peroxidation. 5. Reduced glutathione (0.1-1.0 mM) was shown to decrease the rate of lipid peroxidation in rat liver microsomes, but did not affect its level in mitochondria. 6. Pyrazole injections to rats reduced and phenobarbital treatment increased the level of the Bu'OOH-dependent lipid peroxidation in liver microsomes. 7. The data obtained indicate that the Bu'OOH-dependent lipid peroxidation is not an appropriate marker of the ethanol-induced oxidative stress in rat liver cells.     

Lipid hydroperoxide levels in the heart and liver of rats of various ages

The level of lipid hydroperoxides and secondary products of peroxide oxidation of lipids reacting with 2-thiobarbituric acid (TBA) has been studied in the heart and liver of Wistar male rats aged 1, 3, 12 and 24 months. It is shown that the both indices in the heart lower in the pubertal period of ontogenesis and do not vary with the further ageing. The content of hydroperoxides in the liver is unchanged and that of secondary TBA-active products decreases with the age.     

Intensity of peroxidation processes and activity of antioxidant enzymes in rat tissues at high chromium level in the diet

The data on the influence of chromium in different tissues of rats at its consumption with mixed fodder in the form of CrCl3 x 6H2O on the intensity of peroxidation processes and activity of antioxidant enzymes are presented. The degree of high chromium content in the studied tissues of rats at its addition to mixed fodder in the amount of 200 microg/kg during 30 days was established. Chromium content in the rat tissues decreased in the order: the spleen, heart, kidneys, lungs, brain, liver, skeletal muscle. In all tissues of rats fed with mixed fodder with chromium addition, except for skeletal muscles, content of lipid peroxidation products--hydroperoxide and TBARS-products decreased. The content of lipid peroxidation products decreased in the spleen, kidneys, liver and lungs. Also in all organs and tissues of rats the activity of glutathione peroxidase, glutathione reductase and catalase increased at the action of chromium. In the brain and kidneys the level of reduced glutathione increased. Superoxide dismutase activity was significantly higher not only in the heart and skeletal muscles of animals and is probably equal in the lungs and liver, and in other organs--the brain, kidneys and spleen in animals of the studied group the enzyme activity was lower as compared to animals of the control group. Obtained results demonstrate the regulatory influence of chromium on free radical process in the rat tissues.     

Effect of liposomal antitumor preparation 5,6-benzocoumarin-5-uracil on intensity of free-radical processes in the liver microsomes and tumor cells of rats with transplanted Guerin's carcinoma

The contents of primary and secondary (TBA-active) products of lipid peroxidation were investigated in microsomal fraction of the liver and tumor cells of rats with transplanted Guerin's carcinoma and under the condition of antitumor liposomal preparation 5,6-benzcumarine-5-uracil (BCU) action. High level of lipid peroxidation process in the microsomal fraction is shown in the rat liver and tumor cells under the condition of BCU action in the period of intensive carcinoma growth. It remains till the period of tumor growth braking. This fact testifies to the prooxidation action of the preparation. Liposomal antitumor preparation BCU raises the process of lipid peroxidation in microsomal fraction of tumor cells and its action increases according to the malignant growth. The processes of lipid peroxidation in microsomal rat liver fraction approach the control data under the condition of the mentioned preparation. The investigated liposomal form of BCU possesses directed prooxidation action on the malignant tissue.     

State of the free-radical oxidation system in normobaric hypoxia]

The experiments on the rats have revealed that 7-hour action of 10% hypoxic gas mixture (HGM-10) exerts no effect on the parameters of Fe(2+)-induced chemiluminescence and rate of accumulation of TBA-active products in the heart, liver, kidney, brain tissues and blood plasma. Two-week adaptation to intermittent effect of HGM-10 causes some activation of free-radical oxidation recorded in blood plasma and the more pronounced increase in power of the endogenic antioxidant system. It is assumed that the revealed changes in the state of the homeostatic system of free-radical oxidation and antiradical protection of the organism are of importance in the mechanism of the known preventive and curative action of intermittent normobaric hypoxia.     

Effect of aliphatic aldehydes on the lipid peroxidation and chemiluminescence of biological systems under oxidative stress

The effect of several aliphatic aldehydes on lipid peroxidation was evaluated by measuring the oxygen uptake rate, thiobarbituric acid-reactive products formation and the emitted visible chemiluminescence intensity. Measurements were carried out in brain homogenates and erythrocyte plasma membrane and liver microsomal fractions. In all systems studied, aldehydes (25 mmol/L) (e.g. acetaldehyde, 2,2-dimethylpropanal), increased the intensity of the luminescence associated with the oxidation process. In contrast, aldehyde incorporation decreased TBARS production and the rate of oxygen uptake. The increased luminescence intensity is explained in terms of secondary reactions of aldehyde derived free radicals. These results clearly indicate that extreme care must be exercized in the intepretation of chemiluminescence data in the presence of aldehydes. © 1997 John Wiley & Sons, Ltd.     

Tissue specificity of lipid peroxidation under emotional stress in rats

The intensity of lipid peroxidation and activity of antioxidant system enzymes in the blood plasma, brain and cardial muscle of laboratory rats under 40 days of isolation and violation of diurnal cycle was studied. The obtained data show that on the background of concentration changes in NO changes also take place in the intensity of lipid peroxidation process, indicated by changes in the concentration of TBA-active products and diene conjugates. The changes taking place in the activity of superoxidedismutase, catalase, succinatdehydrogenase, creatine kinase and aldolase under stress were studied. The resulting data show that isolation of animals and violation of diurnal cycle are the factors causing a significant reduction in the energy metabolism in the brain and heart tissue cells and resulting in oxidative stress that, in its turn, may become the reason for development of toxic radicals. Furthermore, prolonged stress may result in irreversible processes that are considered to be the reasons for significant pathologies of the cardiovascular system.     

Antioxidative effect of ursodeoxycholic acid in the liver of rats with oxidative stress caused by gamma-irradiation

We studied effects of ursodeoxycholic acid (UDCA) (10 and 100 mg/kg b.w.) on the free radical generation, lipid peroxidation and the antioxidant defense system in the liver of rats with oxidative stress caused by gamma-irradiation. Both doses of UDCA normalized the liver parameters enhanced by gamma-irradiation: the content of superoxide anion and carbonyl-containing products of lipid peroxidation (alkanals, alkenals, alkadienals and ketones), the superoxide dismutase activity and the chemiluminescence enhanced by luminol. Only the highest dose of UDCA (100 mg/kg b.w.) decreased the chemiluminescence enhanced by lucigenin in liver microsomes and the hydroxyalkenals content in the liver. UDCA prevented reduced glutathione depletion caused by gamma-irradiation, whereas glutathione-related enzyme activities did not change under the influence of both the UDCA doses as well as gamma-irradiation. Thus, the data obtained suggest that UDCA is a metabolite having the sufficiently effective antioxidant properties.     

Age-dependent lipid peroxidation in neonatal rat lung tissue.

A unique, age-specific pulmonary lipid peroxidation has been found to occur after incubation of neonatal rat lung homogenates in the absence of any added factors. As measured by the formation of malondialdehyde, lipid peroxidation was not detectable in rat lung homogenates prepared from animals immediately after birth but appeared by the second day and reached a maximum at 5 days of age. The effect gradually disappeared by 20 to 21 days after birth. The addition of NADPH did not enhance lipid peroxidation in the sensitive age group nor did it initiate lipid peroxidation when added to lung homogenates from either 1-day-old or adult rats. The activities and concentrations of various endogenous antioxidants were measured in neonatal lung tissue. When measured in lung tissue obtained from rats during the sensitive age period, no concomitant deficiencies of glutathione peroxidase, glutathione reductase, glucose 6-phosphate dehydrogenase, reduced glutathione, or a-tocopherol were observed. With the exception of α-tocopherol, none of these factors inhibited malondialdehyde formation when added to homogenized lung tissue prepared from 5-day-old rats. α-Tocopherol did inhibit malondialdehyde formation in 5-day-old rat lung homogenates but at a concentration much greater than the endogenous concentration found in adult rat lungs. The 21-day neonatal age period during which malondialdehyde is produced following incubation of lung tissue is similar to the 3-week period immediately after birth reported to be the time of maximum proliferation of rat lung fibroblasts, type 1 pneumocytes and type II pneumocytes.     

Effect of splenosid on lipid peroxidation process and glutathione antioxidant system in rats exposed to fractionated radiation

The dynamics of lipid peroxidation, antioxidant glutathione system condition in blood and viscerals (brain, heart, liver, spleen) of rats which were fractionally irradiated (10 fractions) in the total dose 1.0 Gy and oxidative homeostasis increase of primary and secondary lipid peroxidation products and glutathione system disturbances were established in the irradiated rats. The administration of splenosid diminished the disturbances of oxidative homeostasis but does not completely normalize the latter. The administration of splenosid during the irradiation course and after its finishing is more effective than only during the irradiation course.     

Effect of various thiamine supplies of the body on the enzyme activity in the metabolism of xenobiotics and lipid peroxidation in rat liver microsomes

The effect of different thiamine supply of the organism on the enzymic activity in metabolism of xenobiotics and the processes of the lipid peroxidation in the liver microsomes with the application of phenobarbital, an inductor of microsomes' enzymes are studied in experiments on Wistar albino male rats. It is established that deficit of vitamin B1 increases the activity in most of processes studied in microsomes and also the intensity of lipids' peroxidation. Phenobarbital enhances the activity of microsomal oxidation irrespectively of vitamin B1 supply, whereas peroxidation of lipids is activated by phenobarbital only in animals fed on physiological doses of vitamin B1. The N-demethylation rate of dimethylaniline in experiments in vitro is inhibited by high doses of thiamine (150 microM), its derivatives inhibited this process in low concentrations (15 microM) as well.     

Effect of chronic ethanol treatment on lipid peroxidation in rat liver homogenate and subcellular fractions

1. The effect of chronic ethanol treatment on the level of lipid peroxidation in rat liver homogenate and subcellular fractions was measured using chemiluminescence technique and malondialdehyde formation. 2. It was shown that after chronic ethanol treatment the level of Fe/ADP-ascorbate-induced lipid peroxidation was decreased in the whole and "postnuclear" liver homogenates. Dilution of the homogenates prevented depressive effect of ethanol on lipid peroxidation. 3. Chronic ethanol treatment did not affect the intensity of the Fe/ADP-ascorbate-induced process in rat liver mitochondria and microsomes. 4. Peroxidative alteration of the liver lipids in vivo was evaluated by measurement of conjugated dienes (absorbance at 233 nm). It was shown that ethanol did not increase the level of u.v. absorption of lipids from mitochondria and microsomes. Chronic alcohol treatment did not influence the steady-state concentration of malonic dialdehyde in the whole liver homogenate. 5. The data obtained indicate that cytosol from the ethanol treated rat liver contains a factor(s) which prevents Fe/ADP-ascorbate-dependent lipid peroxidation in biological membranes.     

Enhancement of lipid peroxidation in rat liver on acute exposure to styrene and acrylamide a consequence of glutathione depletion

Lipid peroxidation, glutathione level and activity of glutathione-S-transferase were studied in liver and brain of rats 4 and 3 h after a single i.p. administration of 0, 25, 75, 100 mg/kg acrylamide or 0, 50, 100, 200, 600 mg/kg styrene, respectively. In liver both acrylamide and styrene caused an increase in lipid peroxidation and decrease in glutathione contents and activity of glutathione-S-transferase in a dose dependent manner, while in brain only acrylamide produced a decrease in glutathione content. The decrease in glutathione content was not always associated with increase of lipid peroxidation. The enhancement of lipid peroxidation occurred only when glutathione contents were depleted to certain critical levels. No effect of acrylamide or styrene was seen on lipid peroxidation under in vitro conditions. The addition of glutathione in the incubation mixture significantly inhibited the rate of lipid peroxidation of liver homogenates of acrylamide and styrene treated animals.The results suggest that enhancement of lipid peroxidation in liver on exposure to acrylamide or styrene is a consequence of depletion of glutathione to certain critical levels. The inhibition of glutathione-S-transferase activity by acrylamide and styrene suggests that detoxication of these neurotoxic compounds could be suppressed following acute exposure.     

Effect of clofibrate treatment on lipid peroxidation in rat liver homogenate and subcellular fractions

1. A study was made of the effect of hypolipidemic drug clofibrate on the level of lipid peroxidation in homogenates and subcellular fractions of rat liver. The intensity of lipid peroxidation was measured using chemiluminescence technique and malondialdehyde formation. 2. It was shown that under the action of clofibrate the levels of Fe/ADP-ascorbate-, as well as t-butyl hydroperoxide (Bu'OOH)-induced lipid peroxidation were decreased in the whole and "post-nuclear" liver homogenates. Dilution of the homogenates prevented depressing effect of clofibrate on lipid peroxidation. 3. Clofibrate significantly decreased the level of the Bu'OOH-dependent lipid peroxidation, but did not affect the activity of the Fe/ADP-ascorbate-induced reaction in rat liver mitochondria and microsomes. 4. Peroxidative alteration of membrane lipids in vivo was evaluated by determining the extent of conjugated dienes formation (absorption at 233 nm). It was shown that clofibrate did not increase the level of ultraviolet absorption of lipids from rat liver subcellular fractions. 5. The data obtained indicate that cytosol from the clofibrate treated rat liver contains a factor(s) which prevents lipid peroxidation in the mitochondria and microsomes.     

Oxidative stress: damage to intact cells and organs

Oxidative cell damage can be monitored by detection of (a) photoemission of singlet molecular oxygen formed from radical interactions (so-called low-chemical chemiluminescence), (b) end products of lipid peroxidation, such as ethane, and (c) glutathione disulphide release. These methods, preferably used in a complementary fashion, provide insight into the pro-oxidant-antioxidant balance in the intact cell or organ. Recent work from this laboratory on the metabolism of hydroperoxides and aldehydes as well as on redox cycling of the quinone menadione is presented. The comparison of GSSG transport systems in liver and heart reveals a limitation of capacity in the latter, thus making GSSG export potentially critical in the heart. As part of an inter-organ feedback system between extrahepatic tissues and liver, the newly described hormone stimulation of GSH release from liver is also presented.     

Comparison of melatonin, vitamin E and L-carnitine in the treatment of neuro- and hepatotoxicity induced by thioacetamide

This study was designed to evaluate and compare the effect of melatonin, vitamin E and L-carnitine on brain and liver oxidative stress and liver damage. Oxidative stress and hepatic failure were produced by a single dose of thioacetamide (TAA) (150 mg kg(-1)) in Wistar rats. A dose of either melatonin (3 mg kg(-1)) vitamin E (20 mg kg(-1) ) or L-carnitine (100 mg kg(-1)) was used. Blood samples were taken from the neck vasculature in order to determine ammonium, blood urea nitrogen (BUN) and liver enzymes. Lipid peroxidation products, glutathione (GSH) content and antioxidative enzymes were determined in cerebral and hepatic homogenates. The results showed a decrease in BUN and in the antioxidant enzymes activities and GSH in the brain and liver. Likewise, TAA induced significant enhancement of lipid peroxidation products levels in both liver and brain, as well as in ammonia values. Melatonin, vitamin E and L-carnitine, although melatonin more significantly, decreased the intensity of the changes produced by the administration of TAA alone. Furthermore melatonin combined with TAA, decreased the ammonia levels and increased the BUN values compared with TAA animals. Also it was more effective than vitamin E or L-carnitine in these actions. These data show the protective effect of these agents, especially melatonin, against oxidative stress and hepatic damage present in fulminant hepatic failure.     

Intensification of lipid peroxidation upon damage to cell membranes]

It is shown that during sensitized by haematoporphyrin photooxidation accumulation of TBA-active products in destroyed cells (human erythrocytes, rat thymocytes, pig leucocytes) occurs considerably faster than in the intact ones. Similar acceleration is observed in intact erythrocytes after the amount of reduced glutathione in it was decreased. It is supposed that the cause of intensification processes of lipid peroxidation consists in separation of the antioxidant system from the plasma membrane.     

Dehydroepiandrosterone protects tissues of streptozotocin-treated rats against oxidative stress

Chronic hyperglycemia in diabetes determines the overproduction of free radicals, and evidence is increasing that these contribute to the development of diabetic complications. It has recently been reported that dehydroepiandrosterone possesses antioxidant properties; this study evaluates whether, administered daily for three weeks per os, it may provide antioxidant protection in tissues of rats with streptozotocin-induced diabetes. Lipid peroxidation was evaluated on liver, brain and kidney homogenates from diabetic animals, measuring both steady-state concentrations of thiobarbituric acid reactive substances and fluorescent chromolipids. Hyperglycemic rats had higher thiobarbituric acid reactive substances formation and fluorescent chromolipids levels than controls. Dehydroepiandrosterone-treatment (4 mg/day for 3 weeks) protected tissues against lipid peroxidation: liver, kidney and brain homogenates from dehydroepiandrosterone-treated animals showed a significant decrease of both thiobarbituric acid reactive substances and fluorescent chromolipids formation. The effect of dehydroepiandrosterone on the cellular antioxidant defenses was also investigated, as impaired antioxidant enzyme activities were considered proof of oxygen-dependent toxicity. In kidney and liver homogenates, dehydroepiandrosterone treatment restored to near-control values the cytosolic level of reduced glutathione, as well as the enzymatic activities of superoxide-dismutase, glutathione-peroxidase, catalase. In the brain, only an increase of catalase activity was evident (p < .05), which reverted with dehydroepiandrosterone treatment. The results demonstrate that DHEA treatment clearly reduces oxidative stress products in the tissues of streptozotocin-treated rats.     

Combined effect of alcohol and cigarette smoke on lipid peroxidation and antioxidant status in rats

The effect of long-term administration of alcohol and cigarette smoke independently and both in combination on lipid peroxidation and antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) was studied in liver, kidney, heart and lungs of albino rats. The levels of peroxidation products viz., malondialdehyde, hydroperoxides and conjugated dienes were increased in all the tissues of alcohol administered and smoke-exposed rats. Activities of SOD and CAT were decreased in alcohol-treated and alcohol and smoke combination groups, but increased in smoke-exposed group. Activities of GPx and GST have shown an increase, while concentration of reduced glutathione was found decreased in all the three groups.