Mechanism of the pro-oxidant activity of tetracycline

It was shown on male rats that like ethanol tetracycline increased lipid peroxidation (LPO) in the hepatocyte membranes, evident from increased levels of diene conjugates and malone dialdehyde in the liver homogenates, especially on their combination. The signal amplitude of the EPR-forms of cytochrome P-450 and Cu-, Mo- and Fe-containing proteins did not change, while the content of the EPR-forms of the free radicals increased. High efficiency of antioxidants, such as tocopherol acetate, sodium selenite and tincture of Astragalus L. is indirect evidence of the role of the free radicals in initiation of LPO in tetracycline affections of the liver.     

Lipid peroxidation in rabbit and rat visual system structures

In our work, the lipid peroxidation (LPO) in the retina, optic chiasma, and visual cortex of rat and rabbit brain was investigated. The contents of the LPO products (diene conjugates, triene conjugates, TBA-reactive products, Schiff bases) and oxidation index (calculated as 232/2 15) were similar in the retina and visual brain cortex of rats. In vivo, lipid oxidation in the optic chiasma was higher as compared with two other parts of visual tract. The similar data were obtained in our experiments with rabbit's visual tract. The sensitivity of tissues to peroxidation in vitro was studied in homogenates incubated with 0.2 mM ascorbate and 10 mkM FeSO4 for 20 min at 37 degrees C. The results of these experiments deviated from the data obtained in vivo, namely: the LPO in optic chiasma was lower than in the retina and the brain cortex. This data are in compliance with lipid composition of investigated parts of the visual tract of both animals. In our opinion, the high level of LPO in optic chiasma demonstrated in vivo is due to low antioxidants level in this part of the visual tract. Our findings also indicate that LPO in retina both in vivo and in vitro experiments are similar to those in the brain cortex and may be attributed to similar lipid composition and activity of antioxidant enzymes (such as superoxiddismutasa and glutathionereductase).     

Antioxidant effects of antihypoxic drugs in cerebral ischemia]

Cerebral ischemia in rats (both carotid arteries occlusion) during 30 min, 3 hours and recirculation (1 hour) after ischemia (30 min) stimulated diene conjugates and fluorescent products accumulation in brain tissue. Intraperitoneal injection of sodium hydroxybutyrate (100 mg/kg), bemitil (50 mg/kg), ethomersol (50 mg/kg) reduced brain lipid peroxidation and did not yield in this respect to emoxypin (5 mg/kg). In contrast to emoxypin, sodium hydroxybutyrate, bemitil and ethomersol had no antiradical activity.     

Lipid peroxidation in cardiac mitochondrial fraction of rats exposed to different supplementation with polyunsaturated fatty acids

The effect of diet supplementation with polyunsaturated fatty acids (PUFAs) used at different ratios of ω-6/ω-3 on the content of primary (diene conjugates, DC; triene conjugates, TC), secondary (ketodienes, CD; coupled trienes, CT; TBA-active products) and terminal (Schiff bases) lipid peroxidation products (LPO) and generation of superoxide anion-radical was studied in rat cardiac mitochondrial fraction. The cardiac mitochondrial fraction of rats kept on a diet with a high content of ω-6 and ω-3 PUFAs for eight weeks was characterized by increased content the primary, secondary and final LPO and a higher rate of superoxide radical formation. In the case of diet supplementation with ω-6 and ω-3 PUFAs used at the ratio of 4: 1, the leading factor determining LPO intensity in the cardiac mitochondrial fraction is a species PUFA composition rather than the degree of saturation.     

Age-related Oxidative Modifications of Proteins and Lipids in Rat Brain

Oxidants have been shown to play a major role in ageing and ageing-related neurodegenerative diseases. In the present study, we investigated the effect of ageing on oxidative damage to lipids and proteins in brain homogenate, mitochondria and synaptosomes of adult (6-month-old), old (15-month-old), and senescent (26-month-old) Wistar rats. There was a significant increase in thiobarbituric acid-reactive substances and conjugated dienes in homogenates, which indicate increased lipid peroxidation (LPO). Oxidative modifications of homogenate proteins were demonstrated by a loss of sulfhydryl content, accumulation of dityrosines and formation of protein conjugates with LPO-end products. Increase in protein conjugates with LPO-end products and a decrease in SH groups were observed also in mitochondria and synaptosomes, but dityrosine content was elevated only in synaptosomes. Protein surface hydrophobicity, measured by fluorescent probe 1-anilino-8-naphthalenesulfonate (ANS), was increased only in homogenate. These results suggest that besides mitochondria and synaptosomes other cellular compartments are oxidatively modified during brain ageing.     

Chronic ingestion of ethanol or glucose solutions affects hypothalamic and limbic TRH metabolism in dams and their pups

The effect of chronic ethanol consumption during pregnancy and lactation on thyrotropin releasing hormone (TRH) metabolism was investigated in the hypothalamus and limbic areas of female rats and their weaned pups. Pregnant female rats received ethanol or isocaloric glucose solution during pregnancy either alone, or also during the 3 weeks of lactation. Thyrotropin (TSH) and corticosterone levels were measured in serum; TRH and TRH-gly concentrations were determined in hypothalamus, hippocampus, n.accumbens, frontal cortex and amygdala of dams and pups at 21 days after parturition. Ethanol or glucose consumption during pregnancy and lactation produced a decrease in TSH levels compared with control animals fed at libitum; water replacement during lactation normalized TSH levels only in glucose-fed dams. Pups from ethanol or pair-fed dams showed low weight and increased TSH levels compared with normal rats. Variations in TRH metabolism were detected in limbic areas. Chronic ethanol caused a decrease in the levels of TRH in the hippocampus and frontal cortex of dams. In contrast, glucose chronic ingestion increased TRH content specifically in n.accumbens and amygdala of dams. Most of the variations in TRH content of limbic areas of pups were not specific for glucose or ethanol treatment and correlated with the deleterious effect of the mother's thyroid condition, although some differences were observed depending on pup's gender. These results support the involvement of TRHergic neurons in the limbic system of the female rat exposed to alcohol or glucose during pregnancy and lactation.     

Enzyme histochemical studies on rat amygdala in fetal alcohol syndrome

Histochemical studies were made of the activity of oxidative and hydrolytic enzymes in rat amygdala in FAS (Foetal Alcohol Syndrome). Ethanol in a dose of 9 g/kg/day was administered to rats during pregnancy and lactation in 6% aqueous solution as the only available liquid. The control rats received an equivalent diet in which ethanol was substituted by an equicaloric amount of sucrose. The offsprings were examined at the end of the 6th postnatal week. The activity of the lysosome and membrane enzymes, as well of some enzymes participating in the neurotransmission, was changed. A different decrease of the activity of oxidoreductases of Krebs cycle, glycolysis and pentose cycle was observed. The changes in the enzyme activity in the amygdala in FAS suggest alterations in the metabolism of the nervous tissue, rather than structural damages of cell organelles.     

Lipid peroxidation in experimental allergic encephalomyelitis

Lipid peroxidation (LPO) in the brain and blood of guinea-pigs was studied during experimental allergic encephalomyelitis. The most pronounced activation of LPO in the brain occurred at the 7th day of sensitization with encephalolitogenic emulsion. It manifested by an increase in the content of diene conjugates and malonic dialdehyde, activation of catalase and reduction of superoxide dismutase activity. LPO activation in the blood occurred at the 3th-5th day of sensitization. It is assumed that LPO activation is caused by antigen-antibody reaction that occurs in the blood at the 3d day and in the brain at the 7th day of sensitization.     

Effects of folic acid and amino acids supplementation on zinc intestinal absorption in the progeny of ethanol-treated rats

This study was designed to examine the effects of supplementation with folic acid and amino acids in dams that consumed ethanol during gestation and lactation to see whether there is an improvement in the intestinal absorption of zinc in pup rats on the 21st day after birth. The rats were randomized into two groups: Ethanol-rats (EG) were administered ethanol during the pregnancy and lactation periods; the ethanol-folic acid group (EFG) received a folic acid and amino acid supplement concomitantly with ethanol administration during pregnancy and lactation. The dams were mated to obtain the first offspring. Two sets of experiments were performed on the offspring at 21 days after birth. In general, in the first set, jejunal zinc absorption in the offspring of EG and EFG groups showed a gradual increase along with increased perfusion time at all assayed concentrations. Jejunal zinc absorption expressed as nmol/intestinal surface was higher in the ethanol-folic acid group than in ethanol animals at all assayed concentrations except at 25 microM concentration. In the second set of experiments, distal ileum zinc absorption in the offspring of ethanolfolic acid dams showed a significant increase at all concentrations tested. These results indicate that supplementation of folic acid and amino acids to dams that consume ethanol during gestation and lactation increase serum and milk zinc levels, although the zinc ingestion is lower. In pups of the supplemented dams, the jejunal and ileal absorption of zinc increased; as a consequence, the serum zinc levels increased. The activity of alcohol dehydrogenase, a metaloenzyme dependent on zinc levels, also increased.     

Effects of maternal ethanol consumption during pregnancy or lactation on intestinal absorption of folic acid in suckling rats

A fostering/crossfostering analysis of the effects of maternal ethanol exposure on jejunal and ileal folate absorption was performed. Male and female rats were randomized into two groups. In the first group, ethanol-treated rats received ad libitum 5, 10 and 15% ethanol in the drinking fluid during three successive weeks. A consumption of 20% was maintained in this group for 5 additional weeks. Ethanol-treated rats were mated. Group 2 served as the control. To study the effect of chronic alcoholism during lactation or gestation separately, at birth (2nd day postpartum) control newborns were cross-fostered to ethanol dams (EG), and the pups issued from the ethanol treated mothers were cross-fostered to control dams (CG). Thus, three experimental groups of pups were formed: (1) control pups receiving no treatment during gestation and lactation (CG); (2) pups exposed to ethanol only during gestation (GG); and (3) pups exposed to ethanol only during lactation (LG). At 21 days postpartum the jejunal and distal ileum folate absorption was determined in the offspring rats by a perfusion technique. Milk folic acid levels were determined by an immunoluminometric assay. The results showed an increase in jejunal folic acid absorption in offsprings exposed to ethanol only during the lactation period (LG). However, in pups exposed to ethanol only during the gestation period (GG), the jejunal folic acid absorption was significantly increased only at concentrations of 0.25, 0.5 and 2.5 microM. No free folic acid absorption occurred in the distal ileum of control pups (CG) at day 21 at all assayed concentrations but in offsprings exposed to ethanol only during the gestation or lactation periods absorption did take place. Pups exposed to ethanol during the gestation period (GG) showed decreased values in ileum folic acid absorption at the lowest assayed concentration (0.25 microM) compared to values obtained for pups exposed to ethanol only during lactation (LG). Milk folic acid levels were significantly decreased in the ethanol-fed dams on day 21 of lactation. These results indicate that exposure of rats to ethanol during the lactation period affects more severely postnatal development of intestinal functions than ethanol exposure only during gestation. In summary, both the exposure to ethanol itself and the decrease in folic acid intake caused alterations in the function of the intestinal mucosa in the offspring, which in turn altered absorption time and development. However, the present results do not explain how ethanol stimulated intestinal absorption of folic acid in pups exposed to ethanol during the gestation or lactation periods. Further studies are needed.     

Effect of alimentary factors on the production of primary and final products of lipid peroxidation

In blood plasma, liver, and brain of pubertal female Wistar line rats the level of diene conjugates, fluorescent lipopigments and vitamin E were studied as a function of different diets: control, fish and fish with addition of vitamin E. The obtained results show that in the brain tissue the role of vitamin E as an antioxidant is more pronounced, but dynamical equilibrium between the oxidation substrates and antioxidants after alimentary deficiency of vitamin E is restored in the nervous tissue more slowly than in the liver and blood plasma. In the organism of young animals fluorescent pigments are not accumulated in form of inert products, but behave as normal metabolites.     

Intensity of lipid peroxidation and antioxidant protection system indices during re-adaptation period after long-term space flights at the international space station

In the blood serum of seventeen members of crews which participated in 14 orbital expeditions to the International Space Station with the duration of 125 to 217 days, during the pre-flight period and on the day of landing on the 1st, 7th and 14th days of the rehabilitation period (RP) the content of LPO products was determined, namely diene conjugates (DC), malon dialdehyde (MDA), shiffbases (SB) and the main lipid oxidant - tocopherol (TP). The group of astronauts who made landing in the Space Shuttle spacecraft (8 persons) and the group of astronauts who accomplished space mission in the Soyus TM spacecraft (9 persons) demonstrated a decrease in DC and MDA levels with a rise in TF concentration in the course of the rehabilitation period. Changes in the group of the American spacecraft astronauts were more pronounced. LPO inhibition during the rehabilitation period is recognized [treated] as an adequate reaction to the stress caused by re-adaptation to the ground conditions. Also are discussed probable mechanisms of intergroup differencies in LPO intensity degree: biomembrane phase state changing under the influence of overloads during de-orbiting and stress response intensity during landing in different types of spacecraft.     

Behavioral characteristics and protein synthesis in the brain of rats receiving ethanol with the mother's milk

The authors studied behavioral responses, conditioned reflexes and indices of protein synthesis in the structures of the brain in the progeny of female rats which received ethanol during the period of lactation.     

Protective effects of ascorbic acid, Dl-α-tocopherol acetate, and sodium selenate on ethanol-induced gastric mucosal injury of rats

In this study, the effect of ascorbic acid (vitamin C), Dl-α-tocopherol acetate (vitamin E), and sodium selenate (selenium) on ethanol-induced gastric mucosal injury in rats was investigated morphologically and biochemically. The gastric mucosal injury was produced by administration of 1 mL of absolute ethanol to each rat. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and selenium (0.5 mg/kg) for 3 d 1 h prior to the administration of absolute ethanol. In gastric mucosa of rats given ethanol according to control groups, neuronal nitric oxide expression decreased. This immunoreactivity was much lower in the group given ethanol+vitamin C+vitamin E+selenium than the control group and the ethanol-induced group. Scanning electron microscopic evaluation of the ethanol-induced group, when compared to control groups, revealed degenerative changes in gastric mucosa, whereas a good arrangement in surface topography of gastric mucosa in the group given ethanol + vitamin C+vitamin E + selenium was observed. In the group administered ethanol, a reduction of the stomach glutathione (GSH) and serum total protein levels and increases in serum sialic acid, triglycerides, and stomach lipid peroxidation (LPO) levels were observed. Vitamin C+vitamin E+Se administration to alcohol-treated rats significantly increased the serum total protein, triglyceride levels, and stomach GSH levels and significantly lowered the levels of serum sialic acid and stomach LPO compared to untreated alcohol-supplemented rats. As a result of these findings, we can say that the combination of vitamin C, vitamin E, and selenium has a protective effect on ethanol-induced gastric mucosal injury of rats.     

Effects of acute stress on lateralization of lipid peroxidation in the brain depend on the behavioral typology of rats

Using the "emotional resonance test" albino mongrel male rats were separated for their preference to light or dark space during the cry of a "victim" rat receiving footshock. Rats avoiding the cry of a "victim" by moving to the light space were characterized by higher levels of lipid peroxidation (LPO) products. A short footshock resulted in a dramatic LPO decrease in both hemispheres in the brain of all rats under study, but in rats not avoiding the cry of a "victim" (preferring dark space) "left" asymmetry of LPO increased.     

Lipid peroxidation rate and the antioxidant protection system during the readaptation period after long-term space flights on board the International Space Station

The content of lipid peroxidation (LPO) products (diene conjugates (DC), malondialdehyde (MDA), Schiff bases (SB), and tocopherol (TP, a main lipid antioxidant) were measured in blood serum of 17 astronauts taking part in long-term (125–217 days) missions on board the International Space Station (ISS) during the preflight period, on the day of the landing, and on the 7th and 14th days after landing (the rehabilitation period, RP). A decrease in the DC and MDA levels against a background of an increase in TP has been found in a group of eight astronauts after landing on board the Space Shuttle spacecraft and a group of eight astronauts after a space flight on board the Soyuz TM in the course of RP. The changes in measured indices were more pronounced in the group of astronauts after the space flight on board the Space Shuttle spacecraft. Inhibition of LPO during RP was regarded as an adequate response to readaptation stress to the conditions on earth. The possible mechanisms of differences in the efficiency of LPO inhibition between groups are discussed: the changes in the biomembrane phase state under the conditions of deceleration load during disorbiting and the stressful reaction to landing on board different spacecrafts.     

The inhibition stage of lipid peroxidation during stress

Stress is shown to induce at first the generalized inhibition of lipid peroxidation (LPO), and then the activation of LPO. In brain and blood serum of rats subjected to continuous footshock as well as to restraint stress LPO products decreased and superoxide scavenging activity increased during the initial period of stress, after 1 hour of footshock LPO indices nearly reached normal values, and after 2 hours of footshock the accumulation of LPO products and decrease of superoxide scavenging activity were seen. LPO inhibition was accompanied by accumulation of easy oxidizable brain phospholipids and by depletion of brain cholesterol, during LPO activation brain cholesterol content and cholesterol-phospholipid ratio increased. The content of LPO products--fluorescent Schiff bases in blood plasma of women suffering from algomenorrhea at first decreased (O-12 h) and then dramatically increased (12-24 h) after a onset of pain at the beginning of menstruation. The data suggest that the stage of LPO inhibition precedes its activation during stress.     

Morphometric analysis of brain lesions in rat fetuses prenatally exposed to low-level lead acetate: correlation with lipid peroxidation

The effect of prenatal lead acetate exposure was studied microscopically together with the concentration of lead and lipid fluorescent products (LFP) in the brain of rat fetuses. Wistar rats were intoxicated with a lead solution containing either 160 or 320 ppm of lead acetate solution during 21 days through drinking water. The control group (ten rats) received deionized water for the same period. The rats were killed on gestation day 21 and fetuses were obtained; the placenta, umbilical cord and parietal cortex (Cx), striatum (St), thalamus (Th) and cerebellum (Ce) were collected for measuring tissue lead concentration, LFP as an index of lipid peroxidation and histopathologic examination. Lead contents were increased in placenta, umbilical cord, St, Th and Cx in both lead-exposed groups. Lead exposure increased (LFP) in placenta and umbilical cord, St, Th and Ce as compared to the control group. Histopathological examination showed severe vascular congestion in placenta, the Cx, St, Th and Ce with hyperchromatic and shrunken cells. Interstitial oedema was found in all regions studied of both lead exposed groups. The morphometric evaluation of the studied brain regions showed an absolute decrease in total cell number and increased number of damaged cells and interstitial oedema. Our results show that morphological changes in rat brain are correlated with increased lipid peroxidation, and the lead levels of the umbilical cord, however it is not clear whether oxidative stress is the cause or the consequence of these neurotoxic effects of lead.     

Injected tryptophan increases brain but not plasma tryptophan levels more in ethanol treated rats

In previous studies, long term treatment with ethanol has been shown to enhance brain 5-hydroxytryptamine 5-(HT) metabolism by increasing the activity of the regulatory enzyme tryptophan hydroxylase and or availability of circulating tryptophan secondarily to an inhibition of hepatic tryptophan pyrrolase. In the present study ethanol treatment given for two weeks decreased hepatic apo-tryptophan pyrrolase but not total tryptophan pyrrolase activity in rats. Tryptophan levels in plasma and brain did not increase significantly. But there was a marked increase of 5-HT but not 5-hydroxyindoleacetic acid (5-HIAA) concentration in brain, suggesting a possible increase in the activity of tryptophan hydroxylase. The effect of a tryptophan load on brain 5-HT metabolism was therefore compared in controls and ethanol treated rats. One hour after tryptophan injection (50 mg/kg i.p.) plasma concentrations of total and free tryptophan were identical in controls and ethanol treated rats, but the increases of brain tryptophan 5-HT and 5-HIAA were considerably greater in the latter group. The results are consistent with long term ethanol treatment enhancing brain serotonin metabolism and show that brain uptake/utilization of exogenous tryptophan is increased in ethanol treated rats and may be useful to understand the role and possible mechanism of tryptophan/serotonin involvement in mood regulation.     

Injected tryptophan increases brain but not plasma tryptophan levels more in ethanol treated rats

In previous studies, long term treatment with ethanol has been shown to enhance brain 5-hydroxytryptamine 5-(HT) metabolism by increasing the activity of the regulatory enzyme tryptophan hydroxylase and or availability of circulating tryptophan secondarily to an inhibition of hepatic tryptophan pyrrolase. In the present study ethanol treatment given for two weeks decreased hepatic apo-tryptophan pyrrolase but not total tryptophan pyrrolase activity in rats. Tryptophan levels in plasma and brain did not increase significantly. But there was a marked increase of 5-HT but not 5-hydroxyindoleacetic acid (5-HIAA) concentration in brain, suggesting a possible increase in the activity of tryptophan hydroxylase. The effect of a tryptophan load on brain 5-HT metabolism was therefore compared in controls and ethanol treated rats. One hour after tryptophan injection (50 mg/kg i.p.) plasma concentrations of total and free tryptophan were identical in controls and ethanol treated rats, but the increases of brain tryptophan 5-HT and 5-HIAA were considerably greater in the latter group. The results are consistent with long term ethanol treatment enhancing brain serotonin metabolism and show that brain uptake/utilization of exogenous tryptophan is increased in ethanol treated rats and may be useful to understand the role and possible mechanism of tryptophan/serotonin involvement in mood regulation.