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.     

Lipid peroxidation in rat uterus

Lipid peroxidation in rat uterus has been studied using NADPH- and ascorbate-induced systems. Lipid peroxidation in rat uterus is low as compared to rat liver. Uterus is more sensitive to ascorbate-induced lipid peroxidation than that induced by NADPH. Uterus contains lower amounts of phospholipids and has a lesser degree of unsaturation in lipids. Co-factor studies show that Fe2+ is more important for ascorbate-induced lipid peroxidation. Endometrium is more sensitive to ascorbate-induced lipid peroxidation than myometrium. It also contains more total lipids and phospholipids besides having a higher degree of unsaturation in the lipids as compared to myometrium. Among the subcellular fractions, mitochondria are more prone to ascorbate-induced lipid peroxidation, whereas microsomes are more sensitive to NADPH-induced lipid peroxidation. Uteri from old rats (24 months) and pregnant rats are more resistant to lipid peroxidation than those from 3-month-old control rats. Uterus of pregnant rats contains more factors which inhibit lipid peroxidation and also has a lesser degree of unsaturation in lipids compared with uterus of control rats. The possible consequences of the resistance of uterus to lipid peroxidation, especially during pregnancy and senescence, are discussed.     

Effect of ischemia and reperfusion of the rat brain on lipid peroxidation and the protective effect of antioxidants

The experiments have been performed on 179 Wistar rats to examine the changes in the brain level of lipid peroxidation products upon 5-, 15-, 30- and 60-min ischemia and 5-, 20- and 60-min reperfusion and to study the protective effect of antioxidants. It has been found that ischemia is accompanied by the accumulation of lipid peroxidation products. The content increases by an average of 138-213% of the initial level. Brain reperfusion after 30-min ischemia was accompanied by an increase or maintenance of a high level of lipid peroxidation products. Ionol injection was accompanied by an increase in the survival of rats and prevented the accumulation of lipid peroxidation products after brain ischemia and reperfusion.     

Lipid peroxidation and free Fe2+ during ischemia and reoxygenation of the liver

Ischemia and reoxygenation were experimentally induced in thin liver sections. It has been shown that free iron decompartmentalization takes place 30 min after the induction of ischemia, with no lipid peroxidation activation observed. In reoxygenation, activation of lipid peroxidation and decrease in free iron concentration take place in the liver cells. It is suggested that free iron accumulation in the tissues during ischemia causes lipid peroxidation activation during reoxygenation.     

Protective effect of exogenous coenzyme Q in rats subjected to partial hepatic ischemia and reperfusion.

In a surgical model of liver ischemia lipid peroxidation occurs, as shown by increase of lipid peroxidation end products, endogenous CoQ9 is oxidized and mitochondrial respiration is lowered; however, pre-treatment of the rats by i.p. injection of CoQ10 for 14 days normalizes the above parameters, presumably by way of the observed high extent of reduction of the incorporated quinone; moreover, liver homogenates of the CoQ10-treated rats are more resistant than those of non-treated rats to oxidative stress induced by an azido free radical initiator. This preliminary study suggests that CoQ10 pre-treatment can be of beneficial effect against oxidative damage during liver surgery transplantation.     

Age-related changes in antioxidant enzyme activities in the small intestine and liver from Wistar rats.

The present study was designed to determine age-related changes in intestinal and hepatic antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and glutathione-S-transferase (GST), and lipid peroxidation in male Wistar rats (n = 8) aged 2 wk, 2.5 mon, 5 mon, 10 mon, and 23 mon. In the small intestine, cytosolic SOD, GSH-PX activities and lipid peroxidation were not affected by age, but intestinal GST activity was noticeably enhanced as age increased. In particular, intestinal GST activity in 23 mon old rats was 3 times as strong as that in 2 wk old rats. In the liver, the activity of hepatic cytosolic SOD was not affected by age, whereas GSH-PX and GST activities in rats aged 10 mon and 23 mon were much stronger than those in rats aged 2 wk, 2.5 mon, and 5 mon. The increased lipid peroxidation in 2.5 mon and 5 mon old rats was observed when compared with that of other groups. It is therefore concluded from the results presented here that age greatly increases GST activity in the small intestinal mucosae and increasing GSH-PX, GST activities and lipid peroxidation in the liver from male Wistar rats.     

Sensitivity to in vitro lipid peroxidation in liver and brain of aged rats.

Lipid peroxidation in rat liver and brain has been studied to see if it increases with old age. No significant differences in the level of endogenous, nonstimulated lipid peroxidation (TBA-RS) is found between 9 month-old (mature adults) and 28 month-old animals in liver or cerebral cortex. Liver homogenates subjected in vitro to an oxidative stress (ascorbate-Fe++), show a clearly slower peroxidation rate in old than in young animals. On the other hand, the in vitro peroxidation rate of cerebral homogenates was similar in young and old animals. The in vitro peroxidation rate was much higher in brain than in liver tissue. These results do not support the view that old rats liver and brain are more susceptible to free radical oxidative damage than those of young ones.     

Effect of anaesthetic ether on lipid peroxidation and superoxide dismutase isozymes of young and adult rat brain

Changes in lipid peroxidation and superoxide dismutase level in rat brain due to single exposure to diethyl ether (anaesthetic) were studied in 100 and 300 day old rats. Enhancement of superoxide dismutase activity was more pronounced in young rat brain, while the reverse was the case with lipid peroxidation. The neurotoxic effects of diethyl ether may involve active oxygen species and superoxide dismutase activity increases as a defensive adaptation.     

Age-Related Differences in Synaptosomal Peroxidative Damage and Membrane Properties

Young, adult, and old rats were used to study the effect of age on the integrity and functioning of brain synaptosomes. An evaluation was made of the differences in lipid composition, membrane fluidity, Na+, K(+)-ATPase activity, and susceptibility to in vitro lipid peroxidation. There was an age-related increase in synaptosomal free fatty acids, with no modification in acyl chain composition, and a decrease in membrane phospholipids which increased the cholesterol/phospholipid mole ratio. With altered lipid composition, there was a corresponding age-dependent decrease in membrane fluidity, a reduction of Na+, K(+)-ATPase activity, and an overall greater susceptibility to in vitro lipid peroxidation. Furthermore, lipid peroxidation promoted strong modifications of the membrane fluidity, lipid composition, and Na+,K(+)-ATPase activity just as aging did, thus indicating a possible contribution of oxidative damage to ageing processes. The cases studied revealed that the greater responsiveness of old membranes to in vitro lipid peroxidation resulted in the highest degree of membrane alteration, indicating that all pathological states known to promote a peroxidative injury can have even more dramatic consequences when they take place in old brain.     

Damage to the Ca2+-transport function and the lipid component of the sarcoplasmic reticulum membrane in total ischemia of the rat myocardium

The Ca2+-transporting activity, lipoperoxide chemiluminescence and phospholipid spectrum of sarcoplasmic reticular membranes were studied in ischemic rats. It was shown that a substantial reduction in Ca2+ uptake rate by the sarcoplasmic reticulum occurred within the first 30 minutes and correlated with the increase in chemiluminescence intensity and accumulation of lysophosphatidylcholine. It has been suggested that free radical lipid peroxidation and phospholipase activation are directly related to the reduction of Ca2+-transporting rate by sarcoplasmic reticulum in myocardial ischemia.     

Age-related changes of lipid spectrum, level of lipid peroxidation, and antioxidant defence in the liver and blood of rats

It has been shown that the lowest level of total lipids, cholesterol, triacylglycerols and products of lipid peroxidation of blood and liver, as a rule, is specific to adult rats. These characteristics are significantly higher for old and young animals. At the same time, the level of glutathione and alphatocopherols in adults' liver is much higher than in young and old rats. It suggests the lower level of processes of lipid peroxidation in adult mature rats. The relative high level of products of lipid peroxidation and low content of alpha-tocopherols in old rats' liver (against the background of higher activity and glutamineperoxidase, and glutathionereductase than in adults) suggests tocopherol deficiency in old animals. High content of total lipids, cholesterol and cholesterol entering into the composition of lipoprotein of different density, triacylglycerols, diene conjugates and malonic dialdehide, activity of glutathione-dependent enzymes of antioxidant defence in young animals as compared with these levels in adult rats seems to be associated with agerelated hypercholesterolemia and intensive plastic changes of a growing organism.     

Preventive effect of safranal against oxidative damage in aged male rat brain

An imbalance between production of reactive oxygen species (ROS) and its elimination by antioxidant defense system in the body has been implicated for causes of aging and neurodegenerative diseases. This study was design to assess the changes in activities of antioxidant enzymes (superoxide dismutase (SOD), glutathione-S-transferase (GST), catalase), lipid peroxidation and reduced glutathione (GSH) levels in the brain of 2, 10 and 20 month old rats, and to determine the effect of safranal on the status of selected oxidative stress indices in the 10 and 20 month old rats. The aged rats (10 and 20 months) were given intraperitoneal injections of safranal (0.5 mg/kg day) daily for one month. The results of this study demonstrated that aging caused significant increase in the level of lipid peroxidation as well decrease in the GSH level and activities of SOD and GST in the brain of aging rats. The results of this study showed that safranal ameliorated the increased lipid peroxidation level as well as decreased GSH content of the brain of 10 and 20 month old rats. In addition, safranal treatment to the 20 month old rats, which restored the SOD and GST activities. In conclusion, safranal can be effective to protect susceptible aged brain from oxidative damage by increasing antioxidant defenses.     

Activation of lipid peroxidation and its prevention with ionol during mechanical asphyxia followed by resuscitation

It was shown in experiments on random-bred male rats that during mechanical asphyxia, lipid peroxidation in the brain, heart, lungs and skeletal muscles experiences activation. At the beginning of the resuscitation measures under elevated tissue oxygenation there is a further increase in the intensity of lipid peroxidation, whereas the content of lipid hydroperoxides and Schiff's bases approaches the initial values only after 3 months. It is assumed that excessive activation of lipid peroxidation plays the key role in the pathogenesis of the postresuscitation disease. Preliminary administration of the synthetic antioxidant ionol in a dose of 30 mg/kg reduces activation of lipid peroxidation in all the organs and tissues under study, improves energy supply of the brain and heart, and decreases 3-fold the lethality in the early postresuscitation period.     

Effect of vitamin C on lipid hydroperoxides and carbonyl groups content of rat plasma depending on age and acute heat exposure

Free radicals produced during hyperthermic stress and aging are thought to play an important role in the degenerative process. To investigate the correlation between oxidative damages caused by acute heat exposure or aging, and the protective effect of vitamin C in vivo, we determined the levels of oxidative protein damage, lipid peroxidation, content of endogenous ascorbic acid, and glutathione in the plasma of young and old Wistar rats, subjected or not-subjected to acute heat stress. The results showed that the level of oxidative protein damage (measured as carbonyl content) in plasma was significantly higher in elderly and in heat-exposed animals. Vitamin C treatment led to inhibition on carbonyl production much more pronounced in young heat-exposed than in aged heat-exposed rats. Aging and acute heat exposure correlated positively with increased production of lipid hydroperoxides in rats plasma, but there were no significant differences in lipid hydroperoxides levels between young and old heat-exposed rats, depending on the treatment with vitamin C. Multiple backward regression analysis showed ascorbic acid to be the only determining variable of lipid hydroperoxides levels in unexposed rats. It was concluded that aging and heat exposure instigate an increase of lipid peroxidation and protein oxidation in rat plasma, while vitamin C supplementation significantly counteracts these changes.     

Effect of L-arginine on age-dependent changes of lipid peroxidation processes and antioxidant system activity in rat tissues

The antioxidant system and lipid peroxidation processes under the L-arginine injection were investigated in experiments on the myocardium, liver and blood of rats of different age. Lipid peroxidation processes intensification and antioxidant system enzymes activity decrease in old rats was shown. A pro- and antioxidant property changes which had different specificity and depended on the tissue were investigated. It was concluded that NO-ergic link activated antioxidant protection in old rats, activates antioxidant enzymes but does not influence the antioxidant properties of tissues of young and adult rats.     

L-carnitine protects gastric mucosa by decreasing ischemia-reperfusion induced lipid peroxidation.

Studies have shown that reactive oxygen metabolites and lipid peroxidation play important roles in ischemia-reperfusion injury in many organs such as heart, brain and stomach. The aim of this study is to evaluate the antioxidant effect of L-carnitine on gastric mucosal barrier, lipid peroxidation and the activities of antioxidant enzymes in rat gastric mucosa subjected to ischemia-reperfusion injury. Rats were subjected to 30 min of ischemia followed by 60 min of reperfusion. L-carnitine (100 mg/kg), was given to rats intravenously five minutes before the ischemia. In our experiment, lesion index, thiobarbituric acid reactive substances, prostaglandin E2 and mucus content in gastric tissue were measured. The results indicated that the lesion index and the formation of thiobarbituric acid reactive substances increased significantly with the ischemia-reperfusion injury in the gastric mucosa. L-carnitine treatment reduced these parameters to the values of sham operated rats. The tissue catalase and superoxide dismutase activities and prostaglandin E2 production decreased significantly in the gastric mucosa of rats exposed to ischemia-reperfusion. L-carnitine pretreatment increased the tissue catalase activity and prostaglandin E2 to the levels of sham-operated rats but did not change superoxide dismutase activity. There were no significant difference in glutathione peroxidase activity and mucus content between the groups in the gastric mucosa. In summary, L-carnitine pretreatment protected gastric mucosa from ischemia-reperfusion injury by its decreasing effect on lipid peroxidation and by preventing the decrease in prostaglandin E2 content of gastric mucosa.     

Leukocyte Nurr1 as peripheral biomarker of early-life environmental exposure to permethrin insecticide

The effect of a low dose of the insecticide permethrin administered during early-life was evaluated on leukocytes inflammation mediators on 300- and 500-day-old rats. Nurr1, NF-κB-p65, Nrf2, lipid peroxidation and GSH levels increased with age but compared to the control group, treatment with permethrin induced a significant increase only of Nurr1 and lipid peroxidation in oldest rats. TNF-α and Rantes increased, while IL-1β, IL-2, IL-13 decreased in oldest treated rats. The results propose Nurr1, TNF-α, Rantes, GSH and plasma lipid peroxidation as peripheral biomarkers for monitoring the impact of early-life environmental exposure to xenobiotics in old age.     

The relationship between erythropoietin pretreatment with blood-brain barrier and lipid peroxidation after ischemia/reperfusion in rats

Blood-brain barrier (BBB) leakage plays a role in the pathogenesis of many pathological states of the brain including ischemia and some neurodegenerative disorders. In recent years, erythropoietin (EPO) has been shown to exert neuroprotection in many pathological conditions including ischemia in the brain. This study aimed to investigate the effects of EPO on BBB integrity, infarct size and lipid peroxidation following global brain ischemia/reperfusion in rats. Wistar male rats were divided into four groups (each group n=8); Group I; control group (sham-operated), Group II; ischemia/reperfusion group, Group III; EPO treated group (24 h before decapitation--000 U/kg r-Hu EPO i.p.), Group IV; EPO+ ischemia/reperfusion group (24 h before ischemia/reperfusion--3000 U/kg r-Hu EPO i.p.). Global brain ischemia was produced by the combination of bilateral common carotid arteries occlusion and hemorrhagic hypotension. Macroscopical and spectrophotometrical measurement of Evans Blue (EB) leakage was observed for BBB integrity. Infarct size was calculated based on 2,3,5-triphenyltetrazolium chloride (TTC) staining. Lipid peroxidation in the brain tissue was determined as the concentration of thiobarbituric acid-reactive substances (TBARS) for each group. Ischemic insult caused bilateral and regional BBB breakdown (hippocampus, cortex, corpus striatum, midbrain, brain stem and thalamus). EPO pretreatment reduced BBB disruption, infarct size and lipid peroxide levels in brain tissue with 20 min ischemia and 20 min reperfusion. These results suggest that EPO plays an important role in protecting against brain ischemia/reperfusion through inhibiting lipid peroxidation and decreasing BBB disruption.     

Role of lipid peroxidation in damage to brain neurons during ischemia and in the postischemic period

It has been demonstrated in experiments on rats that highly activated lipid peroxidation in brain tissue during ischemia and early postischemic period gives rise to injuries of membrane structures of neurons and to formation of lysosomes that subsequently aggravate neuronal destruction.     

The effect of complexes of precursors and modulators of coenzyme Q biosynthesis on the functional state of heart mitochondria of old rats

Aging is accompanied by changes in activity of electron-transport enzyme complexes in myocardial mitochondria of old rats and by increased sensitivity of the mitochondrial permeability transition pore (MPTP) to inductors of its opening (Ca²⁺ and phenylarsine oxide). We also observed activation of lipid and protein free-radical peroxidation processes. Administration of a complex of biologically active substances that included precursors and modulators of coenzyme Q biosynthesis (α-tocopherol acetate, 4-hydroxybenzoic acid, and methionine) caused the increase in coenzyme Q content, correction of functional activity of mitochondrial electron-transport chain enzyme complexes, the decrease in intensity of lipid and protein free-radical peroxidation in the heart mitochondria and the decrease in sensitivity of mitochondrial permeability transition pore to inductors of its opening. This complex may be recommended for treatment of mitochondrial dysfunction in various pathologies of cardiovascular system, including in aging.