Paraquat and iron-dependent lipid peroxidation. NADPH versus NADPH-generating systems.

The aim of this work was to study the effect of paraquat (P2+) on NADPH iron-dependent lipid peroxidation (basal peroxidation) either in the presence of NADPH or in the presence of NADPH-generating systems. When NADPH is present, P2+ potentiates NADPH iron-dependent lipid peroxidation, but use of NADPH-generating systems cancels this effect. This may be attributed to certain components in NADPH-generating systems such as glucose-6-phosphate and sodium isocitrate, which act as iron chelators.

Phospholipid fatty acid composition affects enzymatic antioxidant defenses in cultured Swiss 3T3 fibroblasts.

The aim of this work was to study the adaptation of enzymatic antioxidant cell defense to the nature of the membrane polyunsaturated fatty acids (PUFA). 3T3 Swiss fibroblasts were grown for 5 days in a medium supplemented with 50 microM linoleic acid (LA) or eicosapentaenoic acid (EPA) and compared to control cells (C). The phospholipid fatty acid content was evaluated: LA were enriched in n-6 PUFA (27.

Potentiation of iron-induced lipid peroxidation by a series of bipyridyls in relation to their ability to reduce iron.

We determine the relative abilities of three bipyridyls (Paraquat P + +, Benzylviologen B + + and Diquat D + +) to stimulate iron-induced lipid peroxidation in relation to their ability to redox cycle and to reduce iron. The ability to redox cycle increases with the redox potential, in the order: P + + < B + + < D + +. The initial rates of Fe3+ reduction increased from P + + to D + + and B + +.

Plasma and hepatic antioxidant control and vitamin A nutritional status.

Twenty-seven rats were divided into three groups and fed on diets containing 0.3, 6 or 60 RE (retinol equivalent) retinyl palmitate/g food. After 7 weeks, hepatic vitamin A uptake was found to be more efficient in vitamin A-deficient rats than in rats given adequate vitamin A.

Dietary lipid and iron status modulate lipid peroxidation in rats with induced adjuvant arthritis.

We studied the effect of dietary lipids on iron metabolism and lipid peroxidation during induced adjuvant arthritis and/or iron overload in rats. We compared a control diet containing corn oil and rapeseed oil with a diet devoid of polyunsaturated fatty acids containing only tripalmitin as lipids. Four subgroups of rats were used with each diet: without further treatment, with induction of adjuvant arthritis, with iron overload, and with induction of adjuvant arthritis and iron overload.

Paraquat potentiates iron-induced microsomal lipid peroxidation: modulation by the diet lipid composition.

The study concerns the role of two combined factors-lipid composition of the microsomal membranes and the iron concentration in the incubation medium-in lipid peroxidation catalysed by paraquat (P(++)). Rats were subjected to diets containing 5% lipids composed of either tripalmitin (T), peanut oil/rapeseed oil (v/v) (C) or fish oil (F). The level of polyunsaturated fatty acids in the microsomal membranes was higher in C and F than in T.

[Proton magnetic resonance of plasma in the evaluation of systemic effects of cutaneous inflammation in rats].

NMR evaluation of skin rat inflammation, 24 h after UVB exposition and 48 h after vesicatory (croton oil) application, shows significant variations of relaxation times. Cutaneous T1 and T2 are enhanced in both cases, and plasmatic T2 is increased in croton oil inflammation. At the same time, these two inflammations induce in plasma: a significant increase in ceruloplasmin (respectively 70 and 42%); a decrease in iron transferrin (48 and 53%) and iron saturation (%) of transferrin (53 and 68%); an increase in the protein level of 45% for croton oil treated animals.

Microsomal membrane peroxidation by an Fe3+/paraquat system. Consequences of phenobarbital induction.

Descriptions of the effects of paraquat (P2+) on the peroxidation of liver microsomes are very divergent. Therefore, the presence of ferric iron in the medium and the activity of microsomal mixed-function oxidase system are two factors that we have taken into consideration to explain the discrepancies. The results showed that 100 microM P2+ potentializes the slight production of MDA induced by low concentrations of Fe3+ (< or = 15 microM).

Catechin protection of 3T3 Swiss fibroblasts in culture under oxidative stress.

The effects of catechin, a well-known in vitro antioxidant, on 3T3 Swiss fibroblasts are studied under different conditions of oxidative stress leading to cell proliferation or cytotoxicity. Various levels of reactive oxygen species (ROS), generated extracellularly by the xanthine-xanthine oxidase (X-XO) system, are at the origin of the biphasic effect on DNA synthesis by 3T3 Swiss fibroblasts. The addition of 10(-2) U XO/mL, in the absence of exogenous X, catalyzes the production of low levels of O2-.

Ca-efflux, from direct membrane injury by CCl4, is elicited by amphiphilic vehicles in vitro.

Direct membrane injury by CCl4, in situations excluding metabolic activation, was evaluated in saponin-permeabilized hepatocytes and in microsomes by measuring immediate Ca2+ efflux. A good correlation appears between the Ca2+ efflux and the level of CCl4 in the membrane and also the variations in fluidity. Mixtures of CCl4 with water-soluble vehicles were used to improve the dispersion of CCl4 in the medium.

Antioxidant defenses and its modulation by iron in carrageenan-induced inflammation in rats.

The concentration of endogenous antioxidants has been studied in rats with a carrageenan-induced granuloma. This animal model of inflammation allowed us to study the antioxidant defenses and the oxidative stress in plasma and in the site of inflammation (exudate) and their modulation by the levels of iron in the organism after iron-dextran or desferrioxamine administration. In inflamed rats without supplementary treatment, an interrelation between urate, ascorbate and vitamin E levels has been observed and it appears to be an important mechanism to prevent the depletion of the antioxidants.

Hepatic changes during a carrageenan induced granuloma in rats.

Hepatic changes during inflammation were studied in rats bearing a carrageenan induced granuloma. In spite of a decrease in the metabolic capacity of microsomes to induce lipid peroxidation during inflammation, the endogenous lipid peroxidation remained unchanged and unrelated with the hepatic activities measured. The continuous increase in hepatic cAMP observed during acute and chronic phases could be related to adenylate cyclase stimulation by mediators, and could be an initial step in the hepatocyte adaptation leading to the increased level of hepatic caeruloplasmin, to the reduction of cytochrome P-450 level and to the modifications of Ca(2+) sequestration by microsomes.

Superoxide anion scavenging capacity measured by a polarographic method. Comparison with a colourimetric method.

A polarographic method to assess the scavenging capacity of a molecule for O2-. is proposed. This method is based on the fact that O2-.

Carrageenan-induced granuloma and iron status in rats with dietary polyunsaturated fatty acid deficiency.

Sprague-Dawley rats were fed for 4 months on a control diet or a polyunsaturated-fatty-acid (PUFA)-deficient diet. The combined effects of iron overload (Fe dextran) or Fe deficiency (desferrioxamine) on carrageenan-induced granuloma were studied. PUFA deficiency induced changes in Fe metabolism, but no alterations in lipid peroxidation variables were observed.

Implication of membrane functions in toxicology.

The following are defined: the structural and biochemical characteristics of the membrane constituents involved in the functional activity; the importance of the environment of the proteins in the expression of their activity; and the adaptation possibilities of the membrane's functions to the nutritional distortions or to the action of drugs. The membrane's functions, as a hydrophobic barrier and its essential activities, are analysed in relation to their involvement in toxicology with examples of substances having a great specificity of action. On the other hand, the case of substances impairing, in a non-specific way, the membrane's functional state, very frequently the case in food toxicology, is analysed through the modification of the hydrophobic interaction forces that they induce.

Interaction of hexachlorocyclohexane (HCH) and chlorpropham (CIPC) in male rats.

Hexachlorocyclohexane (60.0 mg/kg/d) and chlorpropham (50.0 mg/kg/d) given to male rats daily orally for 30 d caused subtle biochemical lesions.

Nutrition and biomembranes: additional information concerning the incidence of dietary polyunsaturated fatty acids on membrane organization and biological activity.

One of the important questions in biomembranes now is: Do the essential fatty acids (polyunsaturated fatty acids of the n-6 and n-3 series) play an original structural role in the arrangement of the lipid matrix capable, in particular, of triggering modifications of intrinsic protein activities? Preliminary results from our laboratories are presented in rat and piglet fed standard or essential fatty acid-deficient diets. The relative amounts of 18:2 (n-6) and 20:4 (n-6) in total fatty acids of hepatic microsome or enterocyte brush border membrane phospholipids are closely dependent on the type of diet (a globally decreasing effect with deficiency), whereas no differences were observed with relative amounts of cholesterol, phospholipids, and proteins. This effect of deficiency on membrane fatty acids has to be compared to the decreasing specific activities of microsome NADPH-cytochrome c reductase or aniline hydroxylase (studied in rat), to the increasing order of the structure of both membrane microsome and brush border lipid matrix (studied in both rat and piglet), and to the increasing mobility (or accessibility) of the membrane-protein surface-bonded spin-label (studied in the piglet brush border membrane), suggesting a probably defective protein-lipid fit in the case of deficiency.

The effect of dietary essential fatty acid deficiency on the composition and properties of the liver microsomal membrane of rats.

The effect of dietary essential fatty acid (EFA) deficiency on lipid composition, fluidity and important enzyme and transport activities of liver microsomal membrane was studied in weanling rats. After 133 d of EFA deficiency, no difference was noticed in membrane phospholipid, cholesterol and protein levels, but a significant change occurred in the fatty acid composition of bilayer phospholipids. In EFA-deficient rats, linoleic (18:2(n-6] and arachidonic (20:4(n-6] acids were both severely lower while oleic (18:1(n-9], palmitoleic (16:1(n-7] and particularly 5,8,11-eicosatrienoic (20:3(n-9] acids were significantly higher than in controls.

Activity of liver microsomal Ca2+-ATPase in relation to perturbation of membrane hydrophobic interactions induced by methoxybenzene derivatives and n-aliphatic alcohols.

Changes in the activity of liver microsomal Ca2+-ATPase were studied in the presence of two series of lipophilic compounds: four flavouring substances derived from methoxybenzene and four n-aliphatic alcohols. With each compound the activity was stimulated at lower concentrations and inhibited at higher concentrations. The linear relationship between equiactive concentrations of the compounds and their partition coefficients showed that the enzyme activity was modulated by perturbation of membrane hydrophobic interactions.