Lipid Peroxidation In Microsomal Membranes Research Articles

Antioxidant and Hypolipidemic Activities of Cinnamic Acid Derivatives.

Oxidative stress and hyperlipidemia are important factors for the initiation and progression of various cell degenerative pathological conditions, including cardiovascular and neurological diseases. A series of cinnamic acid-derived acids, such as ferulic acid, sinapic acid, 3,4-dimethoxycinnamic acid, p-coumaric acid, and (E)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid, were esterified or amidated with various moieties, bearing different biological activities, and evaluated. The antioxidant and radical scavenging abilities of the compounds via inhibition of rat hepatic microsomal membrane lipid peroxidation, as well as their interaction with the stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), were assessed. Further, their hypolipidemic activity in vivo was tested. The majority of the obtained compounds demonstrated considerable radical scavenging and antioxidant action, with a parallel decrease in Triton-induced hyperlipidemia in rats. The (E)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid derivative with morpholine and 4-methylpiperidine (compounds 4 and 13, respectively) significantly decreased triglycerides and total cholesterol in the plasma of hyperlipidemic rats, with an antioxidant capacity similar to that of the antioxidant Trolox. The compounds were designed to exhibit antioxidant and hypolipidemic pharmacological actions, and this succeeded for the majority of them. Thus, such agents may be of interest in conditions and diseases implicating oxidative stress and dyslipidemia.

Design, Synthesis and Study of Nitrogen Monoxide Donors as Potent Hypolipidaemic and Anti-Inflammatory Agents.

Inflammation and oxidative stress are involved in cardiovascular diseases. Nitrogen monoxide participates in the regulation of endothelial processes. Thus, derivatives of classic nonsteroidal anti-inflammatory drugs (NSAIDs), trolox or cinnamic acids esterified with 2-(nitrooxy)ethanol were designed and studied. It was found that the nitrogen monoxide (NO) releasing activity was comparable to that of S-nitroso-N-acetylpenicillamine. The nitrooxy derivatives decreased potently lipid indices in the plasma of hyperlipidaemic rats (30–85%). All compounds presented increased anti-inflammatory activity in vivo, inhibiting carrageenan-induced rat paw oedema as high as 76%, up to six times higher than that of the parent acids. Lipoxygenase inhibitory activity was significant for most of them, although the parent molecules exerted a minor effect (IC50 > 0.2 mM). Those compounds incorporating an antioxidant structure inhibited rat microsomal membrane lipid peroxidation strongly and possessed radical scavenging activity. These results indicated that the described compounds could act at different targets in multifactorial diseases, further limiting the possible adverse effects of drug combinations.

Anti-inflammatory and Hypolipidemic Effect of Novel Conjugates with Trolox and Other Antioxidant Acids.

A series of esters and amides, incorporating an antioxidant residue, such as trolox or caffeic acid, and various moieties with different biological activities, were synthesised. The obtained compounds demonstrated considerable anti-inflammatory, radical scavenging and antioxidant action. Thus, they could reduce carrageenan-induced rat paw oedema by 31-60% at 150 μmol/kg and inhibit rat microsomal membrane lipid peroxidation with IC50 values as low as 1.4 μM, which is much lower than that of trolox. Most of them could also inhibit soybean lipoxygenase. The thiomorpholine derivatives decreased significantly all lipidemic indices of Triton-induced hyperlipidemia in rats. The most active, the caffeic acid derivative (6), decreases triglycerides, total cholesterol and low density lipoprotein, in the plasma of hyperlipidemic rats, by 70%, 67%, and 73%, respectively, at 150 μmol/kg (i.p.). The synthesised compounds, designed to exhibit two or more pharmacological actions, may be considered useful in the study of agents addressed to conditions involving inflammation and oxidative stress.

Novel polyfunctional esters of ibuprofen and ketoprofen with hypolipidemic, lipoxygenase inhibitory and enhanced anti-inflammatory activity

A series of ibuprofen and ketoprofen esters were designed and synthesised, incorporating an antioxidant moiety, such as quercetin and salicylic alcohol, as well as anti-inflammatory or neuroprotective components. They showed greatly increased activity against carrageenan-induced inflammation, compared with the parent drugs. They could also reduce significantly total cholesterol and triglyceride levels in the plasma of Triton-induced hyperilipidemic rats. Most of them inhibited rat microsomal membrane lipid peroxidation. They also acquire lipoxygenase inhibitory activity and at least two of them could inhibit cyclooxygenases-1/2. 2-Hydroxy-5-(3,5,7-trihydroxy-4-oxo-4H-chromen-2-yl)phenyl 2-(4-isobutylphenyl)propanoate (7), the ester of ibuprofen with quercetin, is the most potent derivative. It is an effective antioxidant, inhibits cyclooxygenases 1/2 and lipoxygenase activity and reduces carrageenan induced paw oedema by 61%. It also decreases triglyceride and total cholesterol levels by 69 and 48%, respectively. The results of this study indicate that proper molecular modifications of non steroidal anti-inflammatory drugs may offer a useful route to potent anti-inflammatory agents, which, in addition, acquire a series of biological properties able to prevent or restore a number of pathological changes in multicausal conditions like the metabolic syndrome.

Antioxidant activity of guaiazulene and protection against paracetamol hepatotoxicity in rats.

The effect of guaiazulene, a lipophilic azulene derivative widely found in nature, on radical-mediated processes is examined. The ability of guaizulene to inhibit rat hepatic microsomal membrane lipid peroxidation and to scavenge hydroxyl radicals, as well as to interact with 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), was estimated. It was found that guaiazulene can inhibit lipid peroxidation very significantly, having an IC50 value of 9.8 microM. It can also scavenge hydroxyl radicals and interact with DPPH. The protection afforded by guaiazulene to rats with paracetamol-induced liver injury was also investigated. Paracetamol hepatotoxicity is caused by the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI), which causes oxidative stress and glutathione (GSH) depletion. Hepatic cytosolic protein, GSH, glutathione transferase and glutathione reductase levels are determined as indices of hepatic injury with or without the administration of guaiazulene. It was found that all parameters affected by paracetamol are restored to normal by guaiazulene treatment, while the administration of guaiazulene alone has no effect on the performed tests compared with the control values. It was concluded that the significant protection against paracetamol-induced GSH depletion and hepatic damage afforded by guaiazulene is probably connected with its antioxidant activity. A molecular mechanism of action of guaiazulene is suggested.

Antioxidant activity of 50% aqueous--ethanol extract from Acantholippia deserticola.

The antioxidant properties oí Acantholippia deserticola, a herb used in traditional northern Chilean medicine was studied using free radical-generating systems. The 50% aqueous-ethanol extract oí Acantholippia deserticola protected against non-enzymatic lipid peroxidation in microsomal membranes of rat, induced by an Fe++-ascorbate system and measured spectrophotometrically by the TBARS test, and had strong free radical scavenging capacities on stable ABTS and DPPH radicals. The results shows that the IC50 value of the 50% aqueous-ethanolic extract of A.deserticola is 18 +/- 0.5 microg/mL in DPPH radical-scavenging, 15 +/- 0.8 microg/mL in lipid peroxidation , Total Antioxidant Activity (TAA) is 0.95 mM of Trolox per mg/mL of extract. The total phenolics content of extract is 725 +/- 12 mg of gallic acid equivalent per g of dried extract. The results indicate that the 50% aqueous-ethanol extract of Acantholippia deserticola clearly has antioxidant properties.

Antioxidant activity of 50% aqueous - ethanol extract from Acantholippia deserticola

The antioxidant properties oí Acantholippia deserticola, a herb used in traditional northern Chilean medicine was studied using free radical-generating systems. The 50% aqueous-ethanol extract oí Acantholippia deserticola protected against non-enzymatic lipid peroxidation in microsomal membranes of rat, induced by an Fe++-ascorbate system and measured spectrophotometrically by the TBARS test, and had strong free radical scavenging capacities on stable ABTS and DPPH radicals. The results shows that the IC50 value of the 50% aqueous-ethanolic extract of A.deserticola is 18 +/- 0.5 microg/mL in DPPH radical-scavenging, 15 +/- 0.8 microg/mL in lipid peroxidation , Total Antioxidant Activity (TAA) is 0.95 mM of Trolox per mg/mL of extract. The total phenolics content of extract is 725 +/- 12 mg of gallic acid equivalent per g of dried extract. The results indicate that the 50% aqueous-ethanol extract of Acantholippia deserticola clearly has antioxidant properties.

In vivo supplementation with Ginkgo biloba protects membranes against lipid peroxidation

The effect of Ginkgo biloba (Gb) supplementation in vivo was studied on lipid peroxidation of microsomal membranes. Administration of up to 100 mg/kg/day Gb to rats did not significantly affect either the activity of microsomal enzymes, the rate of generation of superoxide anion or the iron reduction rate by rat liver microsomes. Lipid peroxidation, assessed by the generation of lipid radicals measured by electron paramagnetic resonance (EPR) spectroscopy using POBN as the spin trap, was reduced by 39.7% and thiobarbituric acid reactive substances (TBARS) generation by 30% after Gb supplementation (100 mg/kg/day) for 10 days. Moreover, membranes from Gb treated animals showed a significant lower content of lipid radicals and TBARS after exposure to oxidative stress both in vitro (t-butyl hydroperoxide) and in vivo (acute iron overload). The data presented here showed that Gb extracts were able to limit lipid peroxidation and scavenge lipid radicals in vivo and actively protect membranes from oxidative damage.

Occurrence of pharmaceutical products in a municipal effluent and toxicity to rainbow trout ( Oncorhynchus mykiss) hepatocytes

Pharmaceutical and personal care products (PPCPs) are found in municipal effluents and represent the major sources of contamination for the aquatic environment. A preliminary chemical analysis of wastewater identified several compounds associated with PPCPs, including caffeine, ibuprofen, naproxen, oxytetracycline, novobiocin, carbamazepine, gemfibrozil, bezafibrate, trimethoprim, sulfamethoxazole, and sulfapyridine. The purpose of this study was to examine the cytotoxic and oxidative effects of these products and other wastewater-related products (i.e., coprostanol, cotinine, estradiol-17 β, nonylphenol, and cholesterol) in primary cultures of rainbow trout hepatocytes. The redox activity of various PPCPs in trout ( Oncorhynchus mykiss) liver microsomes was investigated in vitro by tracking the rate of oxidation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) and the formation of lipid peroxidation (LPO) after a 60-min incubation period. In addition, primary cultures of rainbow trout hepatocytes were exposed to various drugs identified in the municipal effluent for 48 h at 15 °C. Our results show that most PPCPs (83%) accelerated the rate of NADPH oxidation in the presence of microsomes and 72% of them increased LPO in microsomal membranes. LPO levels were significantly correlated ( R = 0.5 ; P < 0.05 ) with the number of functional groups on the molecule's backbone (i.e., number of O, S, N, P/number of C and H) and negatively so ( R = - 0.44 ; P < 0.05 ) with the octanol/water partition coefficient, suggesting that nucleophilicity and hydrophobicity are related to oxidative activity for these compounds. Exposure of trout hepatocytes to these products leads in many cases to decreased cell viability, increased CYP3A-related monooxygenase activity (benzylether resorufin dealkylase), and LPO. No induction of CYP1A1-related activity (7-ethoxyresorufin O-deethylase) was observed. Moreover, municipal effluent extracts (ethanol) were able to increase all the above responses in a dose-dependent manner. These results suggest that the basic redox properties of PPCPs could influence oxidative metabolism in liver cells and lead to oxidative damage. These products have the potential to produce a toxic response in aquatic organisms and the above biomarkers were shown to respond readily to PPCPs in aquatic organisms.

Inhibition of Benzoyl Peroxide–Induced Cutaneous Oxidative Stress, Toxicity, and Ear Edema in Mice by Nardostachys jatamansi.

Recent years have shown considerable efforts to identify new chemopreventive agents that could be of clinical value. In the current study, modulatory effect of Nardostachys jatamansi. (Jones) DC on benzoyl peroxide–induced oxidative stress, toxicity, and ear edema is investigated. Pretreatment with jatamansi at doses of 2.5 and 5 mg/kg body weight in acetone prior to the application of benzoyl peroxide (20 mg/animal per 0.2 ml acetone) resulted in significant inhibition of benzoyl peroxide–induced cutaneous oxidative stress, toxicity, and ear edema in a dose-dependent manner. The cutaneous microsomal membrane lipid peroxidation and xanthine oxidase activities were significantly reduced (p < 0.05). Moreover, the depleted levels of phase II metabolizing enzymes and glutathione were recovered significantly (p < 0.05). Our findings suggest that N. jatamansi. is an effective chemopreventive agent in mouse skin with potential of ameliorating benzoyl peroxide–induced cutaneous oxidative stress, toxicity, and ear edema.

Antioxidant activity of Paraguayan plant extracts

The antioxidant properties of six medical herbs used in the traditional Paraguayan medicine were studied using free radical-generating systems. The methanol extracts from Aristolochia giberti, Cecropia pachystachya, Eugenia uniflora, Piper fulvescens, Schinus weinmannifolia and Schinus terebinthifolia protected against enzymatic and non-enzymatic lipid peroxidation in microsomal membranes of rat. C. pachystachya, E. uniflora, S. weinmannifolia and S. terebinthifolia showed the highest scavenging activity on the superoxide and DPPH radicals.

Indole‐3‐propionic acid, a melatonin‐related molecule, protects hepatic microsomal membranes from iron‐induced oxidative damage: Relevance to cancer reduction

Excessive free iron and the associated oxidative damage are commonly related to carcinogenesis. Among the antioxidants known to protect against iron-induced oxidative abuse and carcinogenesis, melatonin and other indole compounds recently have received considerable attention. Indole-3-propionic acid (IPA), a deamination product of tryptophan, with a structure similar to that of melatonin, is present in biological fluids and is an effective free radical scavenger. The aim of the study was to examine the effect of IPA on experimentally induced oxidative changes in rat hepatic microsomal membranes. Microsomes were preincubated in presence of IPA (10, 3, 2, 1, 0.3, 0.1, 0.01 or 0.001 mM) and, then, incubated with FeCl3 (0.2 mM), ADP (1.7 mM) and NADPH (0.2 mM) to induce oxidative damage. Alterations in membrane fluidity (the inverse of membrane rigidity) were estimated by fluorescence spectroscopy and lipid peroxidation by measuring concentrations of malondialdehyde+4-hydroxyalkenals (MDA+4-HDA). IPA, when used in concentrations of 10, 3 or 2 mM, increased membrane fluidity, although at these concentrations it did not influence lipid peroxidation significantly. The decrease in membrane fluidity due to Fe3+ was completely prevented by preincubation in the presence of IPA at concentrations of 10, 3, 2 or 1 mM. The enhanced lipid peroxidation due to Fe3+ was prevented by IPA only at the highest concentration (10 mM). It is concluded that Fe3+-induced rigidity and, to a lesser extent, lipid peroxidation in microsomal membranes may be reduced by IPA. However, IPA in high concentrations increase membrane fluidity. Besides melatonin, IPA may be used as a pharmacological agent to protect against iron-induced oxidative damage to membranes and, potentially, against carcinogenesis. J. Cell. Biochem. 81:507–513, 2001. © 2001 Wiley-Liss, Inc.

Indole-3-propionic acid, a melatonin-related molecule, protects hepatic microsomal membranes from iron-induced oxidative damage: Relevance to cancer reduction

Excessive free iron and the associated oxidative damage are commonly related to carcinogenesis. Among the antioxidants known to protect against iron-induced oxidative abuse and carcinogenesis, melatonin and other indole compounds recently have received considerable attention. Indole-3-propionic acid (IPA), a deamination product of tryptophan, with a structure similar to that of melatonin, is present in biological fluids and is an effective free radical scavenger. The aim of the study was to examine the effect of IPA on experimentally induced oxidative changes in rat hepatic microsomal membranes. Microsomes were preincubated in presence of IPA (10, 3, 2, 1, 0.3, 0.1, 0.01 or 0.001 mM) and, then, incubated with FeCl(3) (0.2 mM), ADP (1.7 mM) and NADPH (0.2 mM) to induce oxidative damage. Alterations in membrane fluidity (the inverse of membrane rigidity) were estimated by fluorescence spectroscopy and lipid peroxidation by measuring concentrations of malondialdehyde+4-hydroxyalkenals (MDA+4-HDA). IPA, when used in concentrations of 10, 3 or 2 mM, increased membrane fluidity, although at these concentrations it did not influence lipid peroxidation significantly. The decrease in membrane fluidity due to Fe(3+) was completely prevented by preincubation in the presence of IPA at concentrations of 10, 3, 2 or 1 mM. The enhanced lipid peroxidation due to Fe(3+) was prevented by IPA only at the highest concentration (10 mM). It is concluded that Fe(3+)-induced rigidity and, to a lesser extent, lipid peroxidation in microsomal membranes may be reduced by IPA. However, IPA in high concentrations increase membrane fluidity. Besides melatonin, IPA may be used as a pharmacological agent to protect against iron-induced oxidative damage to membranes and, potentially, against carcinogenesis.

Melatonin reduces rat hepatic macromolecular damage due to oxidative stress caused by δ-aminolevulinic acid

δ-Aminolevulinic acid, precursor of heme, accumulates in a number of organs, especially in the liver, of patients with acute intermittent porphyria. The potential protective effect of melatonin against oxidative damage to nuclear DNA and microsomal and mitochondrial membranes in rat liver, caused by δ-aminolevulinic acid, was examined. Changes in 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels, an index of DNA damage, and alterations in membrane fluidity (the inverse of membrane rigidity) and lipid peroxidation in microsomal and mitochondrial membranes, as indices of damage to lipid and protein molecules in membranes, were estimated. Measurements were made in rat liver after a 2 week treatment with δ-aminolevulinic acid (40 mg/kg b.w., every other day). To test the potential protective effects of melatonin, the indole was injected (i.p. 10 mg/kg b.w.) 3 times daily for 2 weeks. 8-OHdG levels and lipid peroxidation in microsomal membranes increased significantly whereas microsomal and mitochondrial membrane fluidity decreased as a consequence of δ-aminolevulinic acid treatment. Melatonin completely counteracted the effects of δ-aminolevulinic acid. Melatonin was highly effective in protecting against oxidative damage to DNA as well as to microsomal and mitochondrial membranes in rat liver and it may be useful as a cotreatment in patients with acute intermittent porphyria.

Protective effects of melatonin against oxidation of guanine bases in DNA and decreased microsomal membrane fluidity in rat liver induced by whole body ionizing radiation.

The aim of the study was to examine the potential protective effect of melatonin against whole body ionizing radiation (800 cGy). Changes in 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels, an index of DNA damage, and alterations in membrane fluidity (the inverse of membrane rigidity) and lipid peroxidation in microsomal membranes, as indices of damage to lipid and protein molecules in membranes, were estimated. Measurements were made in rat liver, 12 h after their exposure to radiation. To test the potential protective effects of melatonin, the indole was injected (i.p. 50 mg/kg b.w.) at 120, 90, 60 and 30 min prior to radiation exposure. Both 8-OH-dG levels and microsomal membrane rigidity increased significantly 12 h after radiation exposure. Melatonin completely counteracted the effects of ionizing radiation. Changes in 8-OH-dG levels and membrane fluidity are early sensitive parameters of DNA and microsomal membrane damage, respectively, induced by ionizing radiation and our findings document the protective effects of melatonin against ionizing radiation.

Influence of structure on the antioxidant activity of indolinic nitroxide radicals

An in vitro study was carried out to verify whether the chain length of a substituent on an indolinic nitroxide could influence its antioxidant activity in different biological environments subjected to oxidative stress. Three distinct indolinic nitroxides were synthesized and compared with vitamin E and Trolox (a hydrophilic analogue of vitamin E), where the only difference between the nitroxides was the length of the hydrocarbon chain in the 2-position of indole, namely 2 (C2), 10 (C10), and 18 (C18) carbons. All the nitroxides were effective in preventing oxidation of bovine serum albumin, but to different extents, with the longer chain derivatives being more efficient. However, the C2 compound was the most efficient in preventing lipid peroxidation in microsomal membranes. The C2 and C18 compounds, Trolox, and vitamin E protected microsomal protein oxidation to the same extent at the highest concentration used (13 μM). The nitroxide with a C10 chain was less effective in this system. The influence of these compounds on the enzymatic activity of two mitochondrial proteins subjected to oxidative stress was also studied by means of oxygraph measurements. Mitochondrial rotenone-sensitive NADH oxidase and succinate oxidase responded differently to Bu tOOH-induced radical chemistry, and the compounds under study also protected the activity of the two enzymes but to different extents. The results clearly demonstrate that indolinic nitroxides are very efficient antioxidants, protecting both lipids and proteins from peroxidation. The indole structure influences the antioxidant efficacy in biological systems. Copyright © 1996 Elsevier Science Inc.

Influence of retinol deficiency and curcumin/turmeric feeding on tissue microsomal membrane lipid peroxidation and fatty acids in rats.

The effect of retinol deficiency and curcumin/turmeric on lipid peroxidation and fatty acid profile was studied in liver, kidney, spleen and brain microsomes of rats. Results revealed an increase in lipid peroxidation in retinol deficient liver by 32%, kidney 30%, spleen 24% and brain 43% compared to the controls. Feeding 0.1% curcumin or turmeric for three weeks in diet to retinol deficient rats reduced the lipid peroxidation respectively to 12.5 or 22.6%, in liver, 23.7 or 24.1% in kidney, 14.4 or 18.0% in spleen and 16.0 or 31.4% in brain. Retinol deficiency lead to a reduction in the essential fatty acids. In liver C18:1 showed a reduction by 45.6%, C18:2 by 31.6% and C20:4 by 22.8%. In kidney C18:1 was reduced by 33.6%, 18:2 by 24.6% and 20:4 by 13.7%. In spleen and brain C18:1 showed a reduction by 10.2% and 33.9%, C18:2 by 37.9% and 12.1% and C20:4 by 15.7% and 35.3% respectively. Curcumin and turmeric fed group showed a significant increase in the abnormally reduced fatty acid levels.

Vitamin E requirement of Penaeus vannamei

An 8-week feeding trial was conducted to determine the dietary vitamin E requirement of the white-legged shrimp, Penaeus vannamei, using semi-purified diets. Shrimp exhibited significantly increased weight gain when fed increasing levels of vitamin E from 0 to 100 mg/kg diet, whereas no significant difference in growth was observed for shrimp fed diets containing vitamin E from 100 to 600 mg/kg. The vitamin E requirement of shrimp based on growth and estimated by the method of broken-line regression was 99 mg/kg diet. There was no difference in survival. The present study also indicated that vitamin E was an effective antioxidant preventing ascorbic acid-stimulated lipid peroxidation in mitochondrial and microsomal membranes, oxidative spoilage of shrimp tail muscle during frozen storage (−60°C) and peroxidation of dietary lipid. Dietary vitamin E levels of approximately 25 and 100 mg/kg diet were found to be required for suppressing ascorbic acid-stimulated mitochondrial and microsomal membrane lipid peroxidation in shrimp hepatopancreas and muscle, respectively. The synthetic antioxidant, butylated hydroxytoluene (BHT), was an effective antioxidant in vitro by protecting dietary lipid from peroxidation, but it was less effective in tissue protection and exhibited no inhibitory effect on ascorbic acid-stimulated mitochondrial and microsomal membrane lipid peroxidation. However, growth reduction of shrimp resulting from vitamin E-deficiency could be prevented by supplementation of BHT at 0.02% of the dietary lipid content.

The effect of heavy metals on processes of lipid peroxidation in microsomal membranes from the hepatopancreas of the bivalve mollusc mizuhopecten yessoensis

1. Studies were performed regarding the effects of cadmium and copper on the lipid peroxide contents and on the initial rates of NADPH-dependent and Fe-ascorbic acid-dependent lipid peroxidation in the microsomes of hepatopancreas of the scallop Mizuhopecten yessoensis exposed to these pollutants for 3 weeks. 2. The results demonstrated that copper accumulation in hepatopancreas cells was accompanied by a significant increase in hydroperoxide and malondialdehyde contents in microsomal membranes, and by alteration in the both enzymic and non-enzymic lipid peroxidation. Cadmium didn't appear to potentiate lipid peroxidation processes in mollusc tissues. 3. Possible reasons for different effects of these metals on lipid peroxidation processes are discussed.

Cytochrome P-450 under conditions of oxidative stress: role of antioxidant recycling in the protection mechanisms.

Free radicals initiate lipid peroxidation of microsomal membranes by rapidly forming lipid hydroperoxides (LOOH) from endogenous polyunsaturated fatty acid residues of phospholipids. Lipid hydroperoxides may in turn propagate lipid peroxidation via the cytochrome P-450-dependent mechanism. Indeed cytochrome P-450 catalyzes the oxidative cleavage of lipid hydroperoxides to a pool of alkoxyl- (LO) and peroxyl-LOO) radicals which induce an additional formation of lipid hydroperoxides. Propagation and termination of lipid peroxidation in the cell are accompanied by a concomitant accumulation of numerous lipid peroxidation products possessing different effects on biomembranes and membrane bound enzymes (Halliwell and Gutteridge, 1985; Kagan, 1988). However, these products originate from hydroperoxides, the primary molecular lipid peroxidation products, which can be reduced to corresponding hydroxy-compounds by peroxidases (Christophersen, 1969; Ursini et al., 1985) thus preventing the formation of various scission products. Lipid peroxidation is considered to be an efficient triggering mechanism of the disassembly of microsomal membranes and cytochrome P-450.