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At least 937 records · Page 52Linked to original sources
PubMed1990

Effects of novel antioxidants on carbon tetrachloride-induced lipid peroxidation and toxicity in precision-cut rat liver slices.

Previous studies in rat liver microsomes have demonstrated the effectiveness of the 21-aminosteroid, U-74,006F, the troloxamine, U-78,517G, and N,N'-diphenyl-p-phenylenediamine (DPPD) in preventing carbon tetrachloride (CCl4)-induced lipid peroxidation. Studies reported here utilized liver slices to assess whether these antioxidants could prevent lipid peroxidation and ensuing toxicity in a more complete/complex system. Liver slices prepared from Aroclor 1254-induced SD rats were incubated in Dulbecco's modified eagle media, 37 degrees C, for up to 9 hr. Slices were preincubated with test compounds for 30 min prior to addition of CCl4. Lipid peroxidation, as measured by the formation of thiobarbituric acid-reactive substances and ethane evolution, was decreased by U-74,006F (100 microM), U-78,517G (100 microM), and DPPD (1 microM). CCl4 (2.5 microliters) decreased intracellular K+ content, intracellular lactate dehydrogenase (LDH), and intracellular isocitrate dehydrogenase (ICD) activities over a 9-hr incubation period. Despite the marked effects on lipid peroxidation, U-74,006F showed no protection against K+ or LDH loss and only moderate protection against ICD loss. U-78,517G showed no protection against K+ loss but substantial protection against enzyme loss. DPPD demonstrated slight protection against K+ and marked protection against enzyme loss. All three compounds inhibited CCl4-induced lipid peroxidation; U-78,517G being most effective, followed by DPPD and U-74,006F. Inhibition of lipid peroxidation provided protection to the membrane structure as indicated by inhibition of LDH and ICD loss. The antioxidants failed to protect against CCl4-induced toxicity (K+ loss). These results suggest that CCl4-induced lipid peroxidation and toxicity may be dissociable.

Animals↗
PubMed1992

The relationship between nickel chloride-induced peroxidation and DNA strand breakage in rat liver.

Inorganic nickel chloride induces hepatic DNA strand breaks, chromosome aberrations, and lipid peroxidation under in vitro and in vivo conditions. The objective of this research was to determine if a relationship exists between NiCl2 genotoxicity and lipid peroxidation in vivo. Male Sprague-Dawley rats (210-250 g) were dosed with 0.56 or 0.75 mmol/kg NiCl2 subcutaneously and euthanized after specific time periods, ranging from 30 min to 24 hr. Livers were perfused and excised for the measurement of nickel content using atomic absorption spectrometry, lipid peroxidation using a thiobarbituric acid assay, and DNA strand breakage using single-stranded DNA extraction and the diaminobenzoic acid assay. The lower dose (0.56 mmol/kg) did not induce lipid peroxidation or strand breakage. The higher dose (0.75 mmol/kg) induced DNA strand breakage at 4 hr and lipid peroxidation at 12 hr in rat liver. Nickel was seen to accumulate in liver nuclei of rats receiving 0.75 mmol/kg. Deferoxamine (1 g/kg, ip, 15 min before the NiCl2 injection) completely inhibited DNA strand breakage at 4 hr but had no effect on lipid peroxidation. This suggests that lipid peroxidation is not causally related to genetic damage. NiCl2-induced DNA strand breakage may be caused by the induction of the Fenton reaction, generating hydroxyl radicals.

Animals↗
PubMed1981

Effect of age and metabolic rate on lipid peroxidation in the housefly, Musca domestica L.

The objective of this study was to explore the mechanism by which metabolic rate may affect life span by determining the relationship between lipid peroxidation potential and experimentally altered life spans in the adult housefly. Lipid peroxidation potential, measured in vitro, provides an indication of the relative conditions within the tissues affecting the susceptibility of polyunsaturated fatty acids to undergo non-enzymic peroxidation. Lipid peroxidation potential increased with age at a significantly faster rate in houseflies raised at 30 degrees C as compared to those kept at 25 degrees C. The life span of flies at 25 degrees C was longer and metabolic rate lower than at 30 degrees C. The effect of physical activity on lipid peroxidation potential was studied by comparing flies maintained under high and low physical activity regimes. Lipid peroxidation potential increased at a relatively greater rate with age in high-activity flies. The results suggest that accelerated senescence associated with higher metabolic rates, increases the rate of age-associated decline in the ability of houseflies to counteract lipid peroxidation in vitro.

Aging↗
PubMed1983

Hepatic aldehyde dehydrogenases and lipid peroxidation.

Recent findings have shown that microsomal membrane lipid peroxidation generates a variety of reactive aldehydic products. The interaction of lipid peroxidation products with hepatic aldehyde dehydrogenases (ALDH) was studied using rat liver subcellular fractions. The well-documented membrane peroxidation product malondialdehyde (MDA) was studied to determine if ALDH isozymes play a role in metabolism of this aldehyde. The cytosolic and mitochondrial hepatic subcellular fractions were found to contain ALDH isozymes capable of oxidizing MDA. The kinetic properties of a cytosolic ALDH (Km of approximately 16 microM) suggest that this enzyme may be involved in the metabolism of MDA in vivo. Both the cytosolic and mitochondrial fractions also contained an ALDH isozyme with Km values in the millimolar range. Addition of the cytosolic fraction of rat liver produced a significant decrease in the accumulation of MDA during CCl4-induced microsomal membrane lipid peroxidation but did not protect cytochrome P-450 from destruction. The mitochondrial low Km ALDH isozyme was found to be a target enzyme for inhibition during in vitro microsomal lipid peroxidation. These studies show that a select ALDH isozyme is sensitive to inhibition during membrane lipid peroxidation whereas other isozymes may be involved in the metabolism of aldehydic peroxidation products.

Aldehyde Dehydrogenase↗
PubMed1994

Peroxidative extent and coenzyme Q levels in the rat: influence of physical training and dietary fats.

Sport practice is widely recognized as capable of producing peroxidative damages, even of severe intensity. Dietary manipulations can also modify membrane susceptibility to peroxidation. In previous experiments we found that, while dietary virgin olive oil successfully protects mitochondrial and microsomal membranes from endogenous, xenobiotics-induced peroxidation, dietary polyunsaturated oils lead to increased peroxidative levels. In the latter conditions, cell machinery tries to counteract the structural and functional changes which have occurred, by modulating enzyme activities and concentrations, by increasing biosynthesis of coenzyme Q and by mobilizing cholesterol. In the present study we hypothesized that combining these two aspects could give useful information on the membrane response to peroxidation phenomena that daily occur throughout the lifespan. Rats fed different dietary oils as only fat source underwent a carefully designed training program and were killed at different times following acute or chronic exercise. Results show that peroxidation related to chronic training and to an acute bout of exercise sum up with peroxidative effects induced by dietary factors. The above mentioned phenomena occurred simultaneously with increased tissue levels of coenzyme Q, possibly triggered within a physiological reactive antioxidant strategy.

Aging↗
PubMed1985

Implication of hydrogen peroxide in the mutagenicity of coffee.

A cup of instant coffee (150 ml) of normal strength (15 mg/ml) was found to contain about 500 and 750 micrograms of hydrogen peroxide soon after its preparation at 37 degrees C and 80 degrees C, respectively, but the concentration of hydrogen peroxide in the coffee increased with time for up to 24 h after its preparation. Thus coffee contains a hydrogen peroxide generating system. As extracts of green coffee beans were found to have very low capacity to generate hydrogen peroxide, this generating system is produced by roasting coffee beans. Hydrogen peroxide itself was only weakly mutagenic to Salmonella typhimurium TA100, but in the presence of methylglyoxal, which is also present as a mutagenic component in coffee, hydrogen peroxide showed strong mutagenicity. Hydrogen peroxide and methylglyoxal seem to be responsible for most of the mutagenicity of instant coffee.

Aldehydes↗
PubMed1986

Inactivation of transforming activity of plasmid DNA by lipid peroxidation.

DNA damage due to NADPH-dependent lipid peroxidation of liposomes was examined using liposomes prepared from lipids, NADPH-cytochrome P-450 reductase and cytochrome P-450 isolated from rat liver microsomes. Plasmid pBR322 DNA was incubated in the reaction mixture for liposomal lipid peroxidation and introduced to Escherichia coli CSR603 (uvrArecA). More of the transforming activity of the DNA was lost as the lipid peroxidation progressed, and this inactivation was dependent on the extent of lipid peroxidation. Single strand breaks occurred in the plasmid DNA. Hydroxyl radical scavengers could not prevent most of the strand breaks or the lipid peroxidation reaction. Chloroform extracts from the reaction mixture of peroxidized microsomes also inactivated the transforming activity of pBR322 DNA but did not cause strand breaks. The 105 000 X g supernatant of the reaction mixture, which contained more than 85% of the thiobarbituric acid-reactive substances, did not inactivate the plasmid DNA. The degradative products of [U-14C]arachidonic acid in the liposomes did not bind to DNA. These results led to the conclusion that at least two types of DNA damaging agent are produced during NADPH-dependent microsomal lipid peroxidation. One induces single strand breaks of DNA and another inactivates the plasmid-transforming activity without inducing strand breaks.

Animals↗
PubMed1992

Increased hydrogen peroxide concentration in human tumor cells due to a nitroxide free radical.

Evidence is presented that the nitroxide free radical, TEMPO, at concentrations commonly used to prevent oxidative damage, increases the intracellular hydrogen peroxide concentration. To investigate the origin of this increased hydrogen peroxide concentration, we have incubated various human tumor cell lines with compounds interfering with the generation of active oxygen metabolites. Sodium azide, inhibitor of the respiratory chain, the iron-chelating agent desferrioxamine, superoxide dismutase and catalase had no effect on the hydrogen peroxide concentration. Metyrapone, inhibitor of the cytochrome P450 system, was demonstrated to decrease, but not completely prevent, the hydrogen peroxide production. N-ethylmaleimide, a sulphydryl-bond alkylating agent, was able to completely prevent the increased hydrogen peroxide production. We conclude that, by increasing the cellular hydrogen peroxide concentration, TEMPO exerts a pro-oxidant effect. This increase in hydrogen peroxide production seems to be mediated by the induction of oxidase activity in the cytochrome P450 system, but other cellular systems involved in electron transport may also play a role.

Catalase↗
PubMed1995

Hydrogen peroxide activation of cytosolic phospholipase A2 in vascular smooth muscle cells.

We have reported previously that hydrogen peroxide induces arachidonic acid release from prelabeled vascular smooth muscle cells. Here, we studied the effect of hydrogen peroxide on the phosphorylation of cytosolic phospholipase A2 in these cells. Hydrogen peroxide induced a rapid, time-dependent increase in the phosphorylation of cytosolic phospholipase A2. Hydrogen peroxide also increased arachidonic acid release from prelabeled cells in a time-dependent manner similar to that of phosphorylation of cytosolic phospholipase A2. Protein kinase C depletion significantly inhibited the hydrogen peroxide-stimulated cytosolic phospholipase A2 phosphorylation and arachidonic acid release. Hydrogen peroxide caused a time-dependent increase in mitogen activated protein kinase activity. Taken together, these findings suggest that cytosolic phospholipase A2 may, at least in part, contribute to arachidonic acid release induced by hydrogen peroxide and this effect appears to be mediated by protein kinase C and mitogen activated protein kinase.

Animals↗
PubMed1988

Protection against carbon tetrachloride hepatotoxicity by 5,10-dihydroindeno[1,2-b]indole, a potent inhibitor of lipid peroxidation.

The influence of 5,10-dihydroindeno[1,2-b]indole (indenoindole) on carbon tetrachloride (CCl4)-mediated hepatotoxicity and lipid peroxidation were examined. Indenoindole (25 mg/kg body weight) ameliorated the increase in liver enzymes appearing in the plasma 24 hr after CCl4 administration, with about a 63% reduction for alanine transaminase, 56% for ornithine transcarbamylase and 84% for alkaline phosphatase. Indenoindole also partially prevented, in a dose-dependent fashion, the decrease in hepatic cytochromes P-450, total tissue reducing equivalents and hepatic ascorbate levels resulting 4 hr after CCl4 administration. In a homogeneous chemical system consisting of purified soybean phospholipid substrate in chlorobenzene, azobisisobutyronitrile-initiated lipid peroxidation was inhibited by indeno-indole, with 50% inhibition occurring at about 17 microM. Inhibition by indenoindole of iron-ascorbate-initiated lipid peroxidation in aqueous buffer containing phospholipid vesicles was about tenfold more efficient, with 50% inhibition occurring at about 1.5 microM. Presumably, this was due to the increased concentration of indenoindole in the membrane of the phospholipid vesicle. The efficiency of inhibition of lipid peroxidation was in the order of indenoindole = butylated hydroxytoluene (BHT) greater than alpha-tocopherol much greater than indole greater than indene. These 50% inhibition values of lipid peroxidation for these compounds were similar in an assay system composed of NADPH-fortified mouse-liver microsomes initiated with CCl4. For indenoindole, the 50% inhibition value (1.3 microM) was more than two orders of magnitude less than the spectral binding constant for indenoindole to mouse-liver cytochrome P-450 (Kd = 236 microM), implying that the partial inhibition of metabolic activation of CCl4 was not responsible for the inhibition of lipid peroxidation observed with indenoindole in this system. It appears that indenoindole may trap reactive radicals and inhibit lipid peroxidation in vitro. Regardless of whether inhibition is at the level of scavenging CCl4 metabolite radicals, or lipid radicals in membranes, radical trapping provides a plausible mechanism by which this compound inhibited CCl4 hepatotoxicity.

Alanine Transaminase↗
PubMed1985

Inhibition of cephaloridine-induced lipid peroxidation.

The present study was designed to elucidate whether cephaloridine-induced lipid peroxidation is inhibited by probenecid, cobalt chloride and antioxidants such as alpha-tocopherol and N,N'-diphenyl-p-phenylenediamine (DPPD). Kidney slices obtained from the renal cortex of male Wistar rats were incubated for 1 h in a cephaloridine or cefotaxime (1.25-10 mg/ml) containing medium. In another series of experiments, kidney slices were incubated with cephaloridine or cefotaxime (5 mg/ml) for different periods of time (30-120 min). Lipid peroxidation was monitored by measuring the production of malondialdehyde (MDA). Subsequently, kidney slices were incubated in both series of experiments, in a cephalosporin free medium containing tetraethylammonium (TEA). Accumulation of TEA in renal cortical slices, expressed as slice to medium ratio (S/M), was used to measure changes in the transport capacity of the kidney cells. While cefotaxime had only a slight effect, cephaloridine induced a significant time- and concentration-dependent increase of MDA production and a significant time- and concentration-dependent decrease of TEA accumulation. Inhibition of the renal uptake of cephaloridine by probenecid induced a decrease in MDA production and complete recovery of TEA accumulation. The antioxidants DPPD and alpha-tocopherol inhibited cephaloridine-induced lipid peroxidation in a concentration-dependent manner. Recovery of TEA accumulation accompanied the decrease in lipid peroxidation. DPPD was a more potent inhibitor of lipid peroxidation than alpha-tocopherol. Cobalt chloride, known for its ability to decrease cellular concentration of cytochrome P-450, effectively decreased cephaloridine-induced lipid peroxidation. Thus, these findings support the concept that lipid peroxidation has an important role in the development of cephaloridine-induced nephrotoxicity.

Animals↗
PubMed1991

Effects of antioxidants on quercetin-induced nuclear DNA damage and lipid peroxidation.

The effects of catalase, superoxide dismutase, mannitol, glutathione, and diallyl sulfide on quercetin-induced DNA damage and lipid peroxidation were investigated in a model system of isolated rat-liver nuclei under aerobic conditions and in the presence of equimolar iron or copper. Mannitol produced a small but significant inhibition of the concurrent nuclear DNA damage and lipid peroxidation induced by quercetin in the presence of iron or copper. Catalase significantly decreased quercetin-induced nuclear DNA damage only in the presence of iron and had no significant effect on lipid peroxidation. Superoxide dismutase showed no significant effect on nuclear DNA damage, but stimulated the quercetin-induced lipid peroxidation only in the presence of copper. Glutathione significantly inhibited the nuclear lipid peroxidation but enhanced the DNA damage. Diallyl sulfide significantly enhanced the nuclear DNA damage but stimulated the lipid peroxidation only in the presence of iron. These results suggest that the reactive oxygen species, especially the hydroxyl radicals, are responsible for the concurrent lipid peroxidation and DNA damage induced by quercetin in the presence of iron or copper in isolated rat-liver nuclei.

Allyl Compounds↗
PubMed1994

Effect of dithiothreitol on lipid peroxidation induced modification of NMDA receptor in fetal guinea pig brain.

The present study examines if the NMDA receptor modification induced by lipid peroxidation is mediated through its redox site and is therefore reversible by dithiothreitol (DTT) by performing [3H]MK-801 binding in the fetal guinea pig brain. P2 membrane fractions were prepared from fetal guinea pig brains and were peroxidized in vitro by 100 microM ascorbate and 25 microM ferric chloride for 20 min. Control and peroxidized membranes were then incubated with 100 microM DTT for 30 min at 37 degrees C. [3H]MK-801 binding was performed in DTT treated and untreated membranes in the presence of 100 microM each of glutamate and glycine. In addition, to study the glutamate- and glycine-dependent activation, [3H]MK-801 binding was determined in the absence (basal) and presence (activated) of glutamate and glycine. Bmax (number of binding sites) and Kd (affinity) of the binding sites were used as indices of NMDA receptor modification and its reversibility by DTT. After lipid peroxidation, the Kd value increased from 4.44 +/- 0.12 in control to 10.39 +/- 1.78 nM (P < 0.01) suggesting decreased affinity following lipid peroxidation. Following treatment with DTT, there was no significant change in Kd, but Bmax was significantly (P < 0.007) decreased in the peroxidized membrane. This suggests that DTT did not improve the affinity of the NMDA receptor of the lipid peroxidized membrane but may have a deleterious effect by reducing the number of binding sites. However, in the control membrane DTT significantly increased the affinity (P < 0.004) and the Bmax (P < 0.01) of the NMDA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effects of taurine and ketamine on bovine retinal membrane lipid peroxidation.

Lipid peroxidation disrupts membrane integrity and causes structural and functional alterations in ischemic tissues. Taurine and ketamine are putative ischemic protectants that affect Ca2+ influx. Here we report the influence of these compounds on lipid peroxidation in subcellular fractions, isolated cells and intact tissue from bovine retinas. P2 membrane fractions and isolated cells were exposed to the lipid peroxidation inducers cadmium chloride (200 microM) or L-ascorbic acid (1 mM) in the presence of 0-50 mM taurine, 0-10 mM ketamine, 1 mM kynurenic acid or 1 mM dextromethorphan. The latter compounds are N-methyl-D-aspartate receptor antagonists. Lipid peroxidation in isolated eyes reperfused after 1 h of ischemia either with or without protectants was determined by thiobarbituric acid assay. Glutathione was measured in isolated retinas subjected in vitro to simulated ischemia (no glucose or oxygenation) for 60 min either alone or in the presence of taurine or ketamine. Ketamine inhibited chemical- or ischemia-induced lipid peroxidation as well as ischemic glutathione depletion. Under the same conditions, taurine failed to affect lipid peroxidation or glutathione. The data show a direct effect of ketamine on lipid peroxidation and point to separate mechanisms of action for ketamine and taurine.

Animals↗
PubMed1992

The importance of peroxide and superoxide in the X-ray response.

Radiation produces a number of damaging radicals as well as peroxide. The chief cellular protection against these radicals, their secondary reactants and peroxide is the cellular glutathione (GSH), GSH peroxidase, GSH-S-transferase (GSHTase), and catalase enzymes. Inhibition of cellular catalase alone does not enhance the aerobic radiation response because cellular GSH peroxidase is equally effective in reducing peroxide. However, inhibition of GSHTase, and partial inhibition of peroxidase by L-buthionine sulfoximine (LBSO)-linked GSH depletion, results in an increased aerobic radiation response. The major pathway for peroxide reduction is the GSH peroxidase. The enzyme is accountable for 70% inactivation of low peroxide concentrations. Catalase accounts for the remaining inactivation. However, it is difficult to assess the relative contributions of GSHTase and peroxidase to the inactivation of radiation-produced hydroperoxides. Our data suggest that GSH depletion results in the inhibition of cellular GSHTase before it inhibits GSH peroxidase. Therefore, part of the increased aerobic radiation response maybe due to cellular inability to reduce hydroperoxides. Peroxide is not a substrate for GSHTase. However, total inhibition of peroxidase by L-BSO plus N-ethylmaleimide (NEM) treatment maximizes the aerobic radiation response. Total inhibition of GSH-S-transferase and peroxidase would block both peroxide and hydroperoxide reduction.

Catalase↗
PubMed1983

Evidence of enhanced in vivo lipid peroxidation after acute cocaine administration.

An acute intraperitoneal dose (60 mg/kg) of cocaine to DBA/2Ha male mice results in enhanced lipid peroxidation in vivo, as measured by an increase in conjugated diene absorption in hepatic microsomal lipids. The initiation of this lipid peroxidation is an early consequence of cocaine administration; as early as 1 h after cocaine, peroxidized lipids are significantly greater in treated animals than in controls. This cocaine-induced lipid peroxidation remains at a maximal level from 2 to 4 h and returns approximately to control levels by 8 h. The metabolites of cocaine also produce lipid peroxidation in vitro. Liver microsomes from phenobarbital-treated DBA/2Ha male mice, incubated aerobically in the presence of NADPH, cocaine or the cocaine oxidative metabolites, norcocaine and norcocaine nitroxide, induced lipid peroxidation as measured by an increase in the production of thiobarbituric acid (TBA)-reactive products. The extent of lipid peroxidation is greater for the oxidative metabolites of cocaine than for cocaine itself.

Animals↗
PubMed1987

The role of iron in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced lipid peroxidation by rat liver microsomes.

Treatment of female Sprague-Dawley rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) enhances hepatic lipid peroxidation, and the role of iron in TCDD-induced lipid peroxidation was examined. Ferrous and ferric ions, and the chelators adenosine diphosphate (ADP), ethylenediaminetetraacetic acid (EDTA) and desferrioxamine (DFX) were added to an in vitro microsomal lipid peroxidation system using microsomes from control and TCDD-treated animals. Both ferrous and ferric ions enhanced microsomal lipid peroxidation, with the greatest effect being produced by the combination of ferrous and ferric ions. The addition of ADP and EDTA produced modest increases in microsomal lipid peroxidation, suggesting that these chelators facilitated formation of reactive oxygen species by iron. The addition of DFX markedly inhibited microsomal lipid peroxidation, with greatest inhibition occurring with microsomes from TCD-treated animals. The results indicate that iron is involved in TCDD-induced lipid peroxidation.

Adenosine Diphosphate↗
PubMed1985

Inhibitory effect of zinc(II) on free radical lipid peroxidation in erythrocyte membranes.

New evidence in support of zinc's role as a membrane antioxidant is presented. Human erythrocyte membranes in buffered saline underwent catalase- and superoxide dismutase-inhibitable lipid peroxidation when incubated with xanthine, xanthine oxidase, and Fe(III). Free radical mediated peroxidation was measured in terms of thiobarbituric acid reactivity and iodometric determination of lipid hydroperoxides. Whereas Ca(II) had relatively little effect on lipid peroxidation, Zn(II) strongly inhibited the reaction and suppressed peroxidation-dependent lysis of resealed membranes. Inhibition of lipid peroxidation was essentially complete in the presence of 0.1 mM Zn(II), a concentration equivalent to that of added Fe(III). By contrast, Zn(II) had no effect on rose bengal-photosensitized lipid peroxidation, a predominantly nonradical, singlet oxygen-driven process. Zinc(II) also interfered with xanthine/xanthine oxidase/iron-induced peroxidation of Triton X-100-dispersed membranes, but had no effect if EDTA was present. Trivial reasons for inhibition, for example, inactivation of xanthine oxidase or complex formation with O2-, were ruled out by showing that the rate of reduction of cytochrome c by xanthine/xanthine oxidase is not affected by Zn(II). We speculate that Zn(II) acts by interfering with the redox cycling of iron, possibly by competing with the latter for membrane binding sites.

Calcium↗