The lipid peroxidation system in the retina and brain of rats during early postnatal ontogeny

The content of the lipid peroxidation products in the rat retina and brain tissues during the early postnatal period (20-45 day of life) was estimated. It was shown during this period the content of conjugated dienes was decreased: the content of malondialdehyde and Schiff bases was without changes in the rat retina. At the same time the content of the conjugated dienes and Schiff bases in the brain tissue was proportionally increased. The activity of glutathioneperoxidase and glutathionereductase was decreased in the retina and not changed in brain. In the same period of the life the content of alpha-tocopherol in the retina was increased. We observed also the enhance of the rate of the induced lipid peroxidation in brain and retina of older animals.     

Monooxygenase system activity and rate of lipid peroxidation in rat liver microsomes in reinduction with polychlorinated biphenyls

Single oral administration of sovol (mixture of polychlorinated diphenyls) caused a significant induction of the liver monooxygenase system (MOS) in rats. The inducing effect persisted for 5 months. Liver MOS responses were similar in repeated and primary sovol administrations. Differences in the morphological liver changes have been detected following single and repeated administrations of sovol.     

Goitres in rats fed polychlorinated biphenyls.

Rats fed a polychlorinated biphenyl (PCB) mixture in a high- or low-iodine diet (HID or LID respectively) for 15 days had thyroid enlargement, low serum thyroxine (T4), and high serum thyrotropin concentrations. Although binding of thyroid hormones to serum proteins was reduced in PCB-fed animals, the free T4 index (reflecting free T4 in serum) was less in these rats. Both serum triiodothyronine (T3) and the free T3 index were elevated in rats fed PCB in HID. LID-maintained rats elevated serum T3 concentrations but the free T3 index was similar to that in HID-fed rats, owing to enhanced binding of thyroid hormone to serum proteins. Addition of PCB to LID reduced serum T3 levels but did not alter the free T3 index because binding was less. In rats fed HID containing PCB, thyroid 131I uptake was increased.     

Alteration of serotonin system by polychlorinated biphenyls exposure

Although commercial production of polychlorinated biphenyls (PCBs) was banned in 1979, PCBs continue to be an environmental and health concern due to their high bioaccumulation and slow degradation rates. In fact, PCBs are still present in our food supply (fish, meat, and dairy products). In laboratory animals, exposure to single PCB congener or to mixtures of different congeners induces a variety of physiological alterations. PCBs cross the placenta and even exposure at low level is harmful for the foetus by leading to neurodevelopment alterations. Serotonin system which regulates many physiological functions from platelet activation to high cerebral processes and neurodevelopment is one of the targets of PCBs toxicity. The effects of PCBs exposure on serotonin system have been investigated although to a lesser extent compared to its effect in other neurotransmitter systems. This review provides a summary of the results concerning the impact of PCBs exposure (in vitro and in vivo) on serotonin system. Further research is needed to correlate specific deficits with PCB-induced changes in the serotonin system.     

Exposure to polychlorinated biphenyls enhances lipid peroxidation in human normal peritoneal and adhesion fibroblasts: A potential role for myeloperoxidase

Nitric oxide, superoxide, and lipid peroxidation (LPO) produced under oxidative stress may contribute to the development of postoperative adhesions. The objective of this study was to determine the effects of polychlorinated biphenyls (PCBs) on LPO, superoxide dismutase, myeloperoxidase (MPO), and nitrite/nitrate in human normal peritoneal and adhesion fibroblasts. PCB treatment reduced inducible nitric oxide synthase (iNOS) expression as well as levels of nitrite/nitrate in both cell lines. Although there was no difference in iNOS expression between the two cell lines, adhesion fibroblasts manifested lower basal levels of MPO compared to normal peritoneal fibroblasts. There was a reduction in MPO expression and its activity in response to PCB treatment in normal peritoneal fibroblasts; however, this effect was minimal in adhesion fibroblasts. Moreover, adhesion fibroblasts manifested higher levels of LPO compared to normal peritoneal fibroblasts, whereas PCB treatment increased LPO levels in both cell types. We conclude that PCBs promote the development of the adhesion phenotype by generating an oxidative stress environment. This is evident by lower iNOS, MPO, and nitrite/nitrate and a simultaneous increase in LPO. Loss of MPO activity, possibly through a mechanism involving MPO heme depletion and free iron release, is yet another source of oxidative stress.     

Vanadium exposure enhances lipid peroxidation in the kidney of rats and mice

Vanadium (V) as sodium orthovanadate induces an increase in lipid peroxidation in the kidneys after a single subcutaneous or intraperitoneal injection to rats or mice. The rate of malondialdehyde (MDA) formation, an index of lipid peroxidation, by kidney homogenates increased by more than 100% 1 h after injection. Chronic exposure of rats to vanadium sulfate, initially through maternal milk and later in the drinking water, resulted after 10 weeks in a significant increase in MDA formation by kidney but not by other tissues. In both acute and chronic studies in rats and mice, no significant increase in lipid peroxidation by V treatment was detected in brain, heart, lung, spleen, or liver. In mice, administration of ascorbate prior to acute exposure to V diminished both toxicity, i.e., respiratory depression and limb paralysis, and the formation of MDA in kidney.     

Skeletal muscle lipid peroxidation in exercised and food-restricted rats during aging

The effects of chronic endurance exercise and food restriction on nonenzymatic lipid peroxidation (LP) of gastrocnemius muscle during aging were studied in male, Fischer 344 rats. One set of rats aged 6 and 18 mo were assigned to an exercise group (treadmill running) or an age-matched sedentary control group. After 6 mo (at the ages of 12 and 24 mo), LP and levels of alpha-tocopherol and its oxidized form, alpha-tocopheryl quinone, were measured. The extent of LP was determined in homogenates by measuring the content of thiobarbituric acid-reactive substances. After homogenization, the muscles were immediately evaluated for basal LP and also incubated in the presence of oxidant stressors for 2 h to assess antioxidant capacity (AOC) and for 24 h to estimate total peroxidizable lipid (TPL). Basal LP was not affected by age or exercise. AOC was not affected by exercise at either age. However aging significantly decreased AOC and increased alpha-tocopheryl quinone in both sedentary and exercised groups. TPL was not affected by age, but was increased by exercise training (P less than 0.05). Another set of rats was divided into the following three groups at 3 mo of age: sedentary, fed ad libitum (S); sedentary, caloric restricted by alternate day feeding (R); and exercised by forced treadmill running (E). Two years later, when the rats were 27 mo of age, the extent of LP was assessed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Responses of antioxidants and lipid peroxidation in mussels to oxidative damage exposure

• 1.1. The aim of this work was to evaluate the relationships between free radical scavengers and lipid peroxidation in the common mussel Mytilus edulis.
• 2.2. Mussels were exposed to compounds known for their ability to produce free radicals (carbon tetrachloride, CCl₄) and reactive oxygen species via redox cycling (menadione), and the effects on digestive gland, gills and remaining tissues were studied.
• 3.3. Lipid peroxidation parameters and the status of free radical scavengers (glutathione, vitamins A, E and C) were affected more by exposure to menadione than to CCl₄.
• 4.4. The observed changes in the free radical scavengers content are indicative of a role in detoxication of damaging reactive species.

     

Diaphragmatic lipid peroxidation in chronically loaded rats

Recent workindicates that free radical-mediated lipid peroxidation takes placewithin the diaphragm on strenuous contraction. This phenomenon has onlybeen demonstrated using fairly artificial experimental models and hasnot been studied during the type of sustained respiratory loadingtypically seen in patients with lung disease. The purpose of thepresent study was to measure the levels of several biochemical markersof protein oxidation (protein carbonyl levels) and lipid peroxidation(8-isoprostane, reduced glutathione, and oxidized glutathione levels)in diaphragms of rats subjected to chronic respiratory loading.Respiratory loading was accomplished by tracheal banding; groups ofanimals were loaded for 4, 8, or 12 days, and a group of sham-operated unloaded animals was used as controls. After loading, animals werekilled, diaphragm contractility was assessed in vitro by using aportion of the excised diaphragm, and the remaining diaphragm and thesoleus muscles were used for biochemical analysis. We found diminishedforce generation in diaphragms from all groups of banded animalscompared with muscles from controls. For example, twitch force averaged7.8 ± 0.8 (SE) N/cm² inunloaded animals and 4.0 ± 0.4, 3.0 ± 0.4, and 3.4 ± 0.4 N/cm² in animals loaded for 4, 8, and 12 days, respectively (P < 0.0001). Loading also elicited increases in diaphragmatic proteincarbonyl concentrations (P < 0.001),and the time course of alterations in carbonyl levels paralleledloading-induced alterations in the diaphragm force-frequencyrelationship. Although loading was also associated with increases indiaphragmatic 8-isoprostane levels (P < 0.003) and reductions in diaphragm reduced glutathione levels (P < 0.003), the time course ofchanges in these latter parameters did not correspond to alterations inforce. Soleus glutathione and carbonyl levels were not altered bybanding. We speculate that respiratory loading-induced alterations indiaphragmatic force generation may be related to free radical-mediatedprotein oxidation, but not to free radical-induced lipid peroxidation.     

Accumulation of polychlorinated biphenyls in adipocytes: selective targeting to lipid droplets and role of caveolin-1

Background

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that preferentially accumulate in lipid-rich tissues of contaminated organisms. Although the adipose tissue constitutes a major intern reservoir of PCBs and recent epidemiological studies associate PCBs to the development of obesity and its related disorders, little is known about the mechanisms involved in their uptake by the adipose tissue and their intracellular localization in fat cells.

Methodology/Principal Findings

We have examined the intracellular distribution of PCBs in mouse cultured adipocytes and tested the potential involvement of caveolin-1, an abundant adipocyte membrane protein, in the uptake of these compounds by fat cells. We show that 2,4,4′-trichlorobiphenyl (PCB-28), 2,3′,4,4′,5-pentachlorobiphenyl (PCB-118) and 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB-153) congeners rapidly and extensively accumulate in 3T3-L1 or mouse embryonic fibroblast (MEF) derived cultured adipocytes. The dynamics of accumulation differed between the 3 congeners tested. By subcellular fractionation of primary adipocytes, we demonstrate that these pollutants were almost exclusively recovered within the lipid droplet fraction and practically not associated to cell membranes. The absence of caveolin-1 expression in primary adipocytes from cav-1 deficient mice did not modify lipid droplet selective targeting of PCBs. In cav-1 KO MEF differentiated adipocytes, PCB accumulation was decreased, which correlated with reduced cell triglyceride content. Conversely, adenoviral mediated cav-1 overexpressing in 3T3-L1 cells, which had no impact on total cell lipid content, did not change PCB accumulation.

Conclusion/Significance

Our data indicate that caveolin-1 per se is not required for selective PCB accumulation, but rather point out a primary dependence on adipocyte triglyceride content. If the crucial role of lipid droplets in energy homeostasis is considered, the almost exclusive accumulation of PCBs in these organelles warrants future attention as the impairment of their function could be linked to the worldwide obesity epidemic.     

多氯联苯的生物修复

多氯联苯(Polychlorinated biphenyls,PCBs)是一种持久性有机污染物,对人类和自然环境具有很大的威胁,降解PCBs一直是研究的热点。在目前的研究方法中生物降解最具潜力,生物降解主要分为微生物降解、植物修复和微生物-植物共同修复3个方面。文章着重介绍了微生物降解PCBs菌株的分离,降解相关基因的克隆和改造;同时对植物修复,植物与微生物共同修复以及植物转基因修复进行了讨论。     

Prenatal exposure to the contaminant perfluorooctane sulfonate elevates lipid peroxidation during mouse fetal development but not in the pregnant dam

Abstract

Perfluorooctane sulfonate (PFOS), a member of the perfluorinated chemical family, has been convincingly demonstrated to affect lipid metabolism in animals and humans and readily crosses the placenta to exert its effects on the developing fetuses. While its exact mechanism is still not clear, PFOS exposure has long been suggested to exert its toxicity via oxidative stress and/or altered gene expression. Levels of PFOS and malondialdehyde in various organs and cell cultures have been widely determined as general indicators of non-specific lipid peroxidation after PFOS exposure. In this study, the oxidation of precise polyunsaturated fatty acids and their metabolites, derived from enzymatic and non-enzymatic pathways was determined following PFOS exposure in both adult and maternal/fetal mice. CD-1 mice were exposed to 3 mg/kg body weight/day of PFOS in corn oil by oral gavage until late gestation (GD17). We demonstrated that lipid peroxidation was particularly and exclusively affected in fetuses exposed to PFOS, but this was not the case in the maternal mice, where limited effects were observed in the enzymatic oxidation pathway. In this study, we demonstrated that PFOS-induced lipid peroxidation might have a greater impact in free radical generation in fetuses than in dams and could be responsible for affecting fetal development. In addition, antioxidant enzymes, such as superoxide dismutase and catalase, appeared to maintain oxidative stress homeostasis partially in adult mice exposed to PFOS. Taken together, our results might elucidate the mechanism of how PFOS induces oxidative stress in vivo.     

Determination of polychlorinated biphenyls in human blood by solid-phase extraction including on-column lipid decomposition

A method for the isolation of polychlorinated biphenyls (PCBs) from human blood using solid-phase extraction (SPE) has been developed. The procedure incorporates decomposition of lipids by concentrated sulphuric acid directly on the SPE column. Conditions for transferring PCBs onto the SPE column and washing the decomposed blood components from the SPE column were optimised. After clean-up the extracts were analysed using gas chromatography with electron capture detection. An average recovery of PCBs from spiked blood samples was about 78±8% and an average precision was about 109±7%. Quantitation has been done using four internal standards and calibration curves based on five concentration levels. Low procedural blanks made it possible to determine PCBs in blood quantitatively at a level down to 2–10 pg g⁻¹. The integrated method for blood is fast, less laborious than methods using liquid–liquid extraction and has a low consumption of organic solvents.     

Responses of antioxidants and lipid peroxidation in mussels to oxidative damage exposure.

1. The aim of this work was to evaluate the relationships between free radical scavengers and lipid peroxidation in the common mussel Mytilus edulis. 2. Mussels were exposed to compounds known for their ability to produce free radicals (carbon tetrachloride, CCl4) and reactive oxygen species via redox cycling (menadione) and the effects on digestive gland, gills and remaining tissues were studied. 3. Lipid peroxidation parameters and the status of free radical scavengers (glutathione, vitamins A, E and C) were affected more by exposure to menadione than to CCl4. 4. The observed changes in the free radical scavengers content are indicative of a role in detoxication of damaging reactive species.     

L-carnitine attenuates doxorubicin-induced lipid peroxidation in rats.

Doxorubicin (DOX) was administered intraperitoneally to rats in six equal, 2.5 mg/kg doses over a 2-week period with or without L-carnitine. Injury was monitored by echocardiography, release of myosin light chain-1 (MLC-1), and by measurement of aldehydic lipid peroxidation products. General observation revealed that DOX alone caused more ascites than DOX plus L-carnitine. Animals sacrificed 2 h after the sixth dose had significantly higher aldehyde concentrations than 2 h after a single dose of DOX. Aldehydes in plasma and heart remained elevated for 3 weeks after the final dose of DOX, whereas L-carnitine prevented or attenuated the DOX-induced increases in lipid peroxidation. The increase in MLC-1 2 h after the sixth dose of DOX was greater than after a single dose, suggesting cumulative damage. Echocardiography did not detect either early injury or the protective effects of L-carnitine. These data indicate that lipid peroxidation following DOX occurs early, and parallels the cumulative characteristics of DOX-induced cardiotoxicity. The protective effects of L-carnitine may be due to improved cardiac energy metabolism and reduced lipid peroxidation.     

Decreased lipid peroxidation in the rat kidney during gestation

Renal malonaldehyde content and lipid peroxidation, induced by ascorbate, NADPH and cumene hydroperoxide, are significantly decreased during gestation in rats. Lipid peroxidation tends to reach normal levels in the kidney post partum. In the renal mitochondria lipid peroxidation without co-factors and that induced by cumene hydroperoxide, ascorbate and NADPH is decreased during pregnancy. However, in the microsomes, only lipid peroxidation induced by NADPH and cumene hydroperoxide is affected. The observed decrease in lipid peroxidation during gestation is reflected by low levels of total lipid and phospholipid. Endogenous inhibitors of lipid peroxidation also increase during pregnancy.     

Hypoxia-induced lipid peroxidation in the brain during postnatal ontogenesis

Reactive oxygen species (ROS) are common products of the physiological metabolic reactions, which are associated with cell signaling and with the pathogenesis of various nervous disorders. The brain tissue has the high rate of oxidative metabolic activity, high concentration of polyunsaturated fatty acids in membrane lipids, presence of iron ions and low capacity of antioxidant enzymes, which makes the brain very susceptible to ROS action and lipid peroxidation formation. Membranes of brain cortex show a higher production of thiobarbituric acid-reactive substances (TBARS) in prooxidant system (ADP.Fe(3+)/NADPH) than membranes from the heart or kidney. Lipid peroxidation influences numerous cellular functions through membrane-bound receptors or enzymes. The rate of brain cortex Na(+),K(+)-ATPase inhibition correlates well with the increase of TBARS or conjugated dienes and with changes of membrane fluidity. The experimental model of short-term hypoxia (simulating an altitude of 9000 m for 30 min) shows remarkable increase in TBARS in four different parts of the rat brain (cortex, subcortical structures, cerebellum and medulla oblongata) during the postnatal development of Wistar rat of both sexes. Young rats and males are more sensitive to oxygen changes than adult rats and females, respectively. Under normoxia or hypobaric hypoxia both ontogenetic aspects and sex differences play a major role in establishing the activity of erythrocyte catalase, which is an important part of the antioxidant defense of the organism. Rats pretreated with L-carnitine (and its derivatives) have lower TBARS levels after the exposure to hypobaric hypoxia. The protective effect of L-carnitine is comparable with the effect of tocopherol, well-known reactive species scavenger. Moreover, the plasma lactate increases after a short-term hypobaric hypoxia and decreases in L-carnitine pretreated rats. Acute hypobaric hypoxia and/or L-carnitine-pretreatment modify serum but not brain lactate dehydrogenase activity. The obtained data seem to be important because the variations in oxygen tension represent specific signals of regulating the activity of many specific systems in the organism.