Activation of guanyl cyclase during lipid peroxidation of biomembranes

The intensity of lipid peroxidation in the microsomal membranes of rat liver influences the activity of "soluble" guanylate cyclase preparations. The increased production of lipid peroxidation products after addition of Fe(II) results in a rise the guanylate cyclase activity; alpha-tocopherol causes a decrease of this activity. An addition of fatty acids hydroperoxides at concentrations above 10(-6) M activates both the membrane-bound and "soluble" guanylate cyclase. It was shown that the hydroperoxide degradation products--carbonyl derivatives responsible for the activation, at concentrations above 10(-9) M provide for activation of the enzyme. The blocking of the SH-groups in "soluble" enzyme preparations by N-ethylmaleimide completely prevents the enzyme activation by carbonyl.     

Erythrocyte lipid peroxidation and antioxidants in cigarette smokers

The present study has analysed the relationship between lipid peroxidation and antioxidant status in erythrocytes from 30 adult male cigarette smokers and an equal number of age and sex-matched normal subjects. Erythrocyte lipid peroxidation was markedly increased. The enzymic antioxidants were decreased in erythrocytes of cigarette smokers. The present study highlights the occurrence of lipid peroxidation and possible breakdown of antioxidant status in cigarette smoking.     

Participation of oxygen activated species in enzymatic lipid peroxidation in biomembranes]

The participation of oxygen activated species in the induction of lipid peroxidation (LPO) in the membrane systems containing cytochrome P-450 (liver microsomes) and in the membrane fragments devoid of this hemoprotein (brain and skeletal muscle microsomes) was studied. It was shown that the rate of NADH-dependent LPO does not depend on the presence of hemoproteins and the activity of NADH-specific flavoprotein in the membranes. On the other hand, the microsomal membranes of the liver with high specific contents of b5 and P-450 cytochromes and NADPH-specific flavoprotein, had the highest rates of NADPH-dependent LPO. It was found that the most effective inhibitors of free oxygen activated species in the case of NADPH- and NADH-dependent LPO in the microsomal fractions of liver, brain and skeletal muscles are the superoxide (O ./2) anion radical inhibitors. The singlet oxygen (1O2) quenchers inhibit only NADPH-dependent LPO in the liver, however, in a far lesser degree. The hydroxyl radical (OH) scavengers had no effect on enzymatic LPO in all systems studied.     

Resveratrol inhibition of lipid peroxidation

To define the molecular mechanism(s) of resveratrol inhibition of lipid peroxidation we have utilized model systems that allow us to study the different reactions involved in this complex process. Resveratrol proved (a) to inhibit more efficiently than either Trolox or ascorbate the Fe2+ catalyzed lipid hydroperoxide-dependent peroxidation of sonicated phosphatidylcholine liposomes; (b) to be less effective than Trolox in inhibiting lipid peroxidation initiated by the water soluble AAPH peroxyl radicals; (c) when exogenously added to liposomes, to be more potent than alpha-tocopherol and Trolox, in the inhibition of peroxidation initiated by the lipid soluble AMVN peroxyl radicals; (d) when incorporated within liposomes, to be a less potent chain-breaking antioxidant than alpha-tocopherol; (e) to be a weaker antiradical than alpha-tocopherol in the reduction of the stable radical DPPH*. Resveratrol reduced Fe3+ but its reduction rate was much slower than that observed in the presence of either ascorbate or Trolox. However, at the concentration inhibiting iron catalyzed lipid peroxidation, resveratrol did not significantly reduce Fe3+, contrary to ascorbate. In their complex, our data indicate that resveratrol inhibits lipid peroxidation mainly by scavenging lipid peroxyl radicals within the membrane, like alpha-tocopherol. Although it is less effective, its capacity of spontaneously entering the lipid environment confers on it great antioxidant potential.     

Stimulation and inhibition of iron-dependent lipid peroxidation by desferrioxamine

Peroxidation of rat brain synaptosomes was assessed by the formation of thiobarbituric acid reactive products in either 50 mM potassium phosphate buffer (pH 7.4) or pH adjusted saline. In phosphate, addition of Fe2+ resulted in a dose-related increase in lipid peroxidation. In saline, stimulation of lipid peroxidation by Fe2+ was maximal at 30 uM, and was less at concentrations of 100 uM and above. Whereas desferrioxamine caused a dose-related inhibition of iron-dependent lipid peroxidation in phosphate, it stimulated lipid peroxidation with Fe2+ by as much as 7-fold in saline. The effects of desferrioxamine depended upon the oxidation state of iron, and the concentration of desferrioxamine and lipid. The results suggest that lipid and desferrioxamine compete for available iron. The data are consistent with the hypothesis that either phosphate or desferrioxamine may stimulate iron-dependent lipid peroxidation under certain circumstances by favoring formation of Fe2+/Fe3+ ratios.     

Resveratrol inhibition of lipid peroxidation

To define the molecular mechanism(s) of resveratrol inhibition of lipid peroxidation we have utilized model systems that allow us to study the different reactions involved in this complex process. Resveratrol proved (a) to inhibit more efficiently than either Trolox or ascorbate the Fe²⁺ catalyzed lipid hydroperoxide-dependent peroxidation of sonicated phosphatidylcholine liposomes; (b) to be less effective than Trolox in inhibiting lipid peroxidation initiated by the water soluble AAPH peroxyl radicals; (c) when exogenously added to liposomes, to be more potent than α-tocopherol and Trolox, in the inhibition of peroxidation initiated by the lipid soluble AMVN peroxyl radicals; (d) when incorporated within liposomes, to be a less potent chain-breaking antioxidant than α-tocopherol; (e) to be a weaker antiradical than α-tocopherol in the reduction of the stable radical DPPH^·. Resveratrol reduced Fe³⁺ but its reduction rate was much slower than that observed in the presence of either ascorbate or Trolox. However, at the concentration inhibiting iron catalyzed lipid peroxidation, resveratrol did not significantly reduce Fe³⁺, contrary to ascorbate. In their complex, our data indicate that resveratrol inhibits lipid peroxidation mainly by scavenging lipid peroxyl radicals within the membrane, like α-tocopherol. Although it is less effective, its capacity of spontaneously entering the lipid environment confers on it great antioxidant potential.     

Inhibition of lipid peroxidation by antioxidants in the vitreous body during hemorrhage

The paper was to investigate the character of malonic dialdehyde content shifts in the vitreous body under the effect of potassium fenosane, oxipyridinchlorhydrate (OPChH), superoxidedismutase, sodium diethylditiokarbamat (DDTK), forming complex with copper under the experimental hemorrhage. Decrease in LPO speed shown after potassium fenosane administration was considerable under retrobulbar administration. More pronounced inhibition of LPO reaction under the hemorrhage was noted in combination of antioxidants with superoxidedysmutase.     

Effect of antioxidants on adriamycin-induced microsomal lipid peroxidation

Adriamycin (25 μM) stimulated NADPH-dependent microsomal lipid peroxidation about fourfold over control values. The tested antioxidants, zinc, superoxide dismutase, vitamin E, and desferrioxamine (Desferal) inhibited Adriamycin-enhanced lipid peroxidation to varying degrees. Others antioxidants, e.g., glutathione, catalase, and selenium, were found to have no effects. Our in vitro studies suggest that adriamycin effect is mediated by a complex oxyradical cascade involving superoxide, hydroxyl radical, and small amounts of iron.     

Studies on spice principles as antioxidants in the inhibition of lipid peroxidation of rat liver microsomes

Polyunsaturated fatty acids (PUFA) are vulnerable to peroxidative attack. Protecting PUFA from peroxidation is essential to utilize their beneficial effects in health and in preventing disease. The antioxidants vitamin E, t-butylhydroxy toluene (BHT) and t-butylhydroxy anisole (BHA) inhibited ascorbate/Fe²⁺-induced lipid peroxidation in rat liver microsomes. In addition, a number of spice principles, for example, curcumin (5–50 µM) from turmeric, eugenol (25–150 µM) from cloves and capsaicin (25–150 µM) from red chillies inhibited lipid peroxidation in a dose-dependent manner. Zingerone from ginger inhibited lipid peroxidation at high concentrations (> 150 µM) whereas linalool (coriander), piperine (black pepper) and cuminaldehyde (cumin) had only marginal inhibitory effects even at high concentrations (600 µM). The inhibition of lipid peroxidation by curcumin and eugenol was reversed by adding high concentrations of Fe²⁺.     

Asbestos-catalysed lipid peroxidation and its inhibition by desferroxamine.

In an effort to understand the properties of asbestos fibres that might contribute to their being toxic, we incubated three different varieties of asbestos with phospholipid emulsions and looked for evidence of lipid peroxidation. Although all three types of asbestos were able to catalyse lipid peroxidation in the native state, this catalytic activity was inhibited by pre-washing of the asbestos with the iron chelator desferroxamine. This suggests that: lipid peroxidation may be one of the mechanisms by which asbestos produces tissue injury, and treatment with iron chelators might diminish the potential to produce this injury.     

Advantages and limitation of BODIPY as a probe for the evaluation of lipid peroxidation and its inhibition by antioxidants in plasma

Oxidative stress and the role of antioxidants are currently one of the most important subjects in the field of life science. In the present study, we assessed the oxidation of plasma lipids induced by free radicals and its inhibition by antioxidants with a fluorescence probe BODIPY. Vitamin E and C-depleted plasma was used to evaluate the inherent action of several antioxidants. BODIPY reacted with free radicals in plasma to emit fluorescence (ex. 510 nm, em. 520 nm), which was suppressed by the antioxidants in a concentration-dependent manner. However, the suppression of fluorescence emission by antioxidants did not always correlate quantitatively with the suppression of lipid peroxidation. For example, alpha-tocopherol suppressed BODIPY fluorescence but enhanced the peroxidation of plasma lipids in the absence of ascorbic acid. 2,2,5,7,8-Pentamethyl-6-chromanol, a vitamin E analogue without a phytyl side chain, almost completely suppressed both fluorescence emission and lipid peroxidation in the plasma. These results show that BODIPY can be used as a convenient probe for radical scavenging, but that care should be taken for the evaluation of antioxidant capacity.     

Nitrofuran inhibition of microsomal lipid peroxidation

Two nitrofuran compounds, nifurtimox and nitrofurantoin, inhibited in a concentration-dependent manner the NADPH-, iron-induced lipid peroxidation in rat liver microsomes, as shown by the decreased rate of MDA accumulation. Other nitro compounds (benznidazole and chloramphenicol) were relatively inactive. Nifurtimox inhibition affected polyenoic fatty acids and cytochrome P-450 degradation that follows lipid peroxidation. The ascorbate- or tert-butyl hydroperoxide-dependent lipid peroxidations were much less inhibited than the NADPH-dependent one. Nifurtimox and nitrofurantoin, but not benznidazole and chloramphenicol, strongly stimulated the microsomal NADPH-oxidase activity, thus supporting electron diversion, as the main cause of the inhibition of peroxidation initiation.     

Normobaric hyperoxic stress in budgerigars: enzymic antioxidants and lipid peroxidation

The effects of acute (3 h), repeated acute (3 exposures each of 3 h) and chronic (72 h) normobaric hyperoxic exposure in budgerigars (Melopsittacus undulatus) were evaluated by monitoring the effects on pulmonary enzymic antioxidants, and indicators of lipid peroxidation. All durations of oxygen exposure resulted in significant respiratory alkalosis and elevated pulmonary and blood glutathione peroxidase concentrations. The concentrations of other pulmonary enzymic antioxidants including glutathione reductase and superoxide dismutase were not significantly altered by oxygen exposure. Pulmonary concentrations of the lipid peroxidation markers malonaldehyde and 4-hydroxyalkenal were not significantly elevated following oxygen exposure. Plasma concentrations of 8-epi isoprostane F(2alpha) were significantly elevated following both acute and repeated acute exposure. The results indicate that in budgerigars, both acute and chronic oxygen exposure can result in significant alteration in respiratory function and increased production of reactive oxygen species.     

Oxidative damage shifts from lipid peroxidation to thiol arylation by catechol-containing antioxidants

Catechol-containing antioxidants are able to protect against lipid peroxidation by nonenzymatic scavenging of free radicals with their catechol moiety. During their antioxidant activity, catechol oxidation products such as semiquinone radicals and quinones are formed. These oxidation products of 4-methylcatechol inactivate the GSH-dependent protection against lipid peroxidation and the calcium sequestration in liver microsomes. This effect is probably due to arylation by oxidation products of 4-methylcatechol of free thiol groups of the enzymes responsible for the GSH-dependent protection and calcium sequestration, i.e. the free radical reductase and calcium ATPase. It is concluded that a catechol-containing antioxidant might shift radical damage from lipid peroxidation to sulfhydryl arylation.     

Inhibition of S-(1,2-dichlorovinyl)-L-cysteine-induced lipid peroxidation by antioxidants in rabbit renal cortical slices: Dissociation of lipid peroxidation and toxicity

Precision-cut, rabbit renal slices were used to examine the effects of three novel antioxidants (U-74006, U-74500, and U-78517) on S-(1,2-dichlorovinyl)-L-cysteine (DCVC)-induced lipid peroxidation and toxicity. Slices exposed to DCVC showed a dose- and time-dependent increase in lipid peroxidation (TBARS) and a decrease in cellular viability, as evidenced by the loss of intracellular potassium, during the course of a 3 hour incubation. Subsequent studies employed DCVC concentrations of 100 μM. Microemulsion formulations of U-78517, U-74500, and U-74006 (100 μM) inhibited DCVC-induced lipid peroxidation by 100±, 50±, and <5% (not significant), respectively. However, none of these antioxidants had a significant effect on DCVC-dependent cytotoxicity, as indicated by intracellular potassium release. The effects of U-78517, the most potent of the three antioxidants, were similar to those observed with two model antioxidants, diphenyl-p-phenylenedi-amine (DPPD) and the iron chelator, deferoxamine. Aminooxyacetic (AOAA), an inhibitor of renal cysteine conjugate β-lyase, had only a minimal effect on DCVC-induced lipid peroxidation, and no effect on toxicity. These data represent the first report of DCVC-induced lipid peroxidation in rabbit renal cortical slices, a system which has been widely used to investigate mechanisms of nephrotoxicity, including that induced by DCVC. Our results demonstrate that DCVC-induced lipid peroxidation in renal slices can be inhibited by a variety of antioxidant compounds operating by different mechanisms. Because inhibition of lipid peroxidation had minimal effect on DCVC-dependent cytotoxicity, the data suggest that DCVC-induced lipid peroxidation is not a major mechanism in the cytotoxicity induced by this compound.     

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.

     

Incorporation of ubiquinones into lipid vesicles and inhibition of lipid peroxidation

Ubiquinone incorporation into vesicles to evaluate its antioxidative effect on lipid peroxidation has been studied. Only sonication and not vortication allows comparable incorporation patterns of the various ubiquinone homologues into lipid vesicles. The measure of malondialdehyde, a convenient index for determining the extent of autoxidation, shows that both the naturally occurring homologues and synthetic shorter-chain ones, also in the oxidized form, possess similar antioxidant efficiency.     

Plasma lipid peroxidation and erythrocyte antioxidants status in workers exposed to nickel

The objectives were to investigate the plasma lipid peroxidation and erythrocyte antioxidants status in workers exposed to nickel. The study groups comprised 69 nickel plating workers and 50 office workers residing in the same city, but away from the place of work of the study group subjects, considered as control group. Urinary nickel concentration was determined by graphite furnace atomic absorption spectrophotometry. The plasma lipid peroxidation and erythrocyte antioxidants were measured by spectrophotmetric methods. The plasma lipid peroxidation level was significantly increased in nickel-platers and their helpers as compared with controls. Erythrocyte antioxidants were significantly decreased in the nickel-platers compared with the controls. The level of plasma lipid peroxidation was positively and erythrocyte antioxidants were negatively and significantly correlated with the urine nickel levels. Multiple regression analysis assessed the oxidative stress associated with nickel and other potential confounding factors such as body mass index, the consumption of green vegetables, coffee, tea, smoking and alcohol consumption. Analysis showed that the lifestyle confounding factors: the consumption of green vegetables, smoking and alcohol, were not significantly associated with oxidative stress. The exposure to nickel, body mass index and coffee consumption were significantly associated with oxidative stress. The results show that the increased plasma lipid peroxidation and decreased erythrocyte antioxidants levels observed in nickel-exposed workers could be used as biomarkers of oxidative stress.     

Plasma lipid peroxidation and erythrocyte antioxidants status in workers exposed to nickel

The objectives were to investigate the plasma lipid peroxidation and erythrocyte antioxidants status in workers exposed to nickel. The study groups comprised 69 nickel plating workers and 50 office workers residing in the same city, but away from the place of work of the study group subjects, considered as control group. Urinary nickel concentration was determined by graphite furnace atomic absorption spectrophotometry. The plasma lipid peroxidation and erythrocyte antioxidants were measured by spectrophotmetric methods. The plasma lipid peroxidation level was significantly increased in nickel-platers and their helpers as compared with controls. Erythrocyte antioxidants were significantly decreased in the nickel-platers compared with the controls. The level of plasma lipid peroxidation was positively and erythrocyte antioxidants were negatively and significantly correlated with the urine nickel levels. Multiple regression analysis assessed the oxidative stress associated with nickel and other potential confounding factors such as body mass index, the consumption of green vegetables, coffee, tea, smoking and alcohol consumption. Analysis showed that the lifestyle confounding factors: the consumption of green vegetables, smoking and alcohol, were not significantly associated with oxidative stress. The exposure to nickel, body mass index and coffee consumption were significantly associated with oxidative stress. The results show that the increased plasma lipid peroxidation and decreased erythrocyte antioxidants levels observed in nickel-exposed workers could be used as biomarkers of oxidative stress.