Lindane-induced liver oxidative stress: respiratory alterations and the effect of desferrioxamine in the isolated perfused rat liver.

The effects of lindane administration (25-60 mg kg-1 for 24 h) on hepatic oxygen consumption were studied in the isolated perfused rat liver, in the absence and presence of the iron-chelator free-radical scavenger desferrioxamine. Lindane elicits a dose-dependent enhancement of total oxygen uptake by the liver, which is largely inhibited by 0.55 mM desferrioxamine.

On the characteristics of the visible chemiluminescence following free radical lipid peroxidation.

The characteristics of the visible luminescence that follows the lipid peroxidative process were investigated either in the autoxidation of rat brain homogenates or in the azo-bis-amidinopropane initiated lipid peroxidation of erythrocyte plasma membranes and liver microsomes. In these systems the luminescence decay observed after total inhibition of the lipid peroxidation is not an iron-catalyzed process, and follows a complex kinetics comprising fast and slow components. The slow component of the decay lasts for several hours at 27 degrees C and amounts to nearly half of the total intensity measured prior to the inhibition of the oxidative process by propyl gallate.

[Active forms of oxygen, oxidative stress and its pathologic significance].

Chemically hyperactive forms of oxygen can induce a variety of functional and morphologic alterations in aerobic organisms. Defensive mechanisms against oxidative damage may be involved in the etiology of pathologic processes induced by oxidative stress. Different antioxidant substances are used in treatment of these conditions.

Antioxidant capacity of diethyldithiocarbamate in a metal independent lipid peroxidative process.

2,2'-Azobis-[2-amidinopropane] initiated lipid peroxidation of egg yolk phosphatydil choline liposomes was measured by oxygen uptake and the emitted visible luminescence. Lipid peroxidation involved a chain process (kinetic chain length = 49 +/- 11) and its rate was independent of added Fe ions. Diethyldithiocarbamate (DDC) behaved as an efficient inhibitor in the microM range, being able to trap 1.

Lindane-induced oxidative stress. II. Time course of changes in hepatic glutathione status.

1. Four hours after treatment of rats with lindane (60 mg/kg), hepatic GSH content was decreased (22%) and GSSG was increased (20%), while biliary concentration and excretion of both GSH and GSSG and bile flow were diminished. These changes coincide with the onset of hepatic lipid peroxidation.

Lindane-induced oxidative stress. I. Time course of changes in hepatic microsomal parameters, antioxidant enzymes, lipid peroxidative indices and morphological characteristics.

1. Lindane (60 mg/kg) administered orally to rats increased liver cytochrome P-450 content and superoxide radical (O2-.) generation 24 h after treatment, while formation of thiobarbituric acid reactants and NADPH/ADP-supported microsomal chemiluminescence were significantly increased 4 h after treatment.

Air pollution impact on phagocytic capacity of peripheral blood macrophages and antioxidant activity of plasma among school children.

Peripheral blood macrophages of school children from downtown Santiago, Chile--a highly polluted city--exhibited a lower phagocytic index with higher percentage of killing than those of the rural village of María Pinto. These findings were observed concomitantly with a lower antioxidant activity of plasma in Santiago students. No differences were observed in serum immunoglobulins (IgA, IgG, and IgM), secretory IgA in saliva, and complement component C3.

Biochemical aspects of cellular oxidative stress.

Oxidative stress, as proposed by H. Sies, indicates a change in the prooxidant/antioxidant balance of a biologic system in favour of the former. It is related to oxidative reactions that occur in aerobic metabolism which can damage biomolecules through generation of reactive oxygen species.

Antioxidant capacity of desferrioxamine and ferrioxamine in the chemically-initiated lipid peroxidation of rat erythrocyte ghost membranes.

2,2'-Azo-bis-(2-amidinopropane) induces the thermal lipid peroxidation of red blood cells membranes by a mechanism that is not iron dependent. The peroxidation rate, as assessed by oxygen uptake or visible chemiluminescence measurements, can be diminished by micromolar concentrations of desferrioxamine (DF), with a median inhibitory concentration (the concentration of DF that reduces the lipid peroxidation rate to 50% of that observed without scavengers addition) of 10 microM. In these conditions, the DF/Fe3+ (1:2) complex is nearly five times less efficient than DF.

Age-dependent changes in in vivo ethanol metabolism and in the activity of hepatic enzymes involved in ethanol oxidation and microsomal functions.

The study of the influence of the age of the animals (13 to 53 weeks) on the rate of ethanol metabolism in vivo and the total activity of liver alcohol dehydrogenase and microsomal ethanol oxidizing system showed a progressive decline with age. These effects were observed concomitantly with a diminution in the content of cytochrome P-450 and microsomal functions related to oxidative and free-radical mediated reactions, namely, NADPH oxidase activity, NADPH-dependent oxygen uptake and NADPH-or t-butyl hydroperoxide-induced chemiluminescence. It is concluded that ageing is accompanied by a diminution in the total oxidative activity of the liver tissue, which would explain the depression in basal and ethanol-induced lipid peroxidation found in the oldest group of rats studied.

Visible chemiluminescence from rat brain homogenates undergoing autoxidation. II. Kinetics of the luminescence decay.

The visible luminescence emitted in the autoxidation of brain homogenates is only partially quenched when antioxidants are added at concentrations such that further oxidation is prevented. From the time course of the emission after antioxidant addition, it can be estimated that nearly 50% of the light arises from an intermediate that decays with a first order kinetics and with a lifetime of ca. 40 s at 32 degrees C.

Increased lipid peroxidation in hyperthyroid patients: suppression by propylthiouracil treatment.

Plasma and urinary levels of thiobarbituric acid reactive substances (TBAR) were determined in 24 hyperthyroid patients, 19 hypothyroid subjects, 35 controls, and 17 hyperthyroid patients before and after propylthiouracil (PTU) treatment (400 mg/day for 2-3 months), as indexes of lipid peroxidation. These measurements were carried out together with t-butyl hydroperoxide (t-BHP)-induced oxygen uptake and visible chemiluminescence in erythrocytes as functional tests related to the antioxigenic capacity of cells. Hyperthyroid patients exhibited increased levels of plasma and urinary TBAR compared to controls.

Chemiluminescent and respiratory responses related to thyroid hormone-induced liver oxidative stress.

Chemiluminescent and respiratory responses were studied in the liver of rats treated with 0.1 mg of triiodothyronine (T3)/kg for 1 to 7 days. Hyperthyroidism resulted in significant increments in the spontaneous chemiluminescence of the in situ liver in animals exhibiting a calorigenic response.

Liver and biliary levels of glutathione and thiobarbituric acid reactants after acute lindane intoxication.

The i.p. administration of 60 mg kg-1 body weight of lindane, the gamma-isomer of hexachlorocyclohexane, to fed rats led to an enhancement of hepatic lipid peroxidation after 24 h of treatment.

Age-dependent changes in rat liver lipid peroxidation and glutathione content induced by acute ethanol ingestion.

The study of the influence of the age of animals (13 to 53 weeks) on total liver thiobarbituric acid reactive substances (TBAR) content showed an increase which is maximal in rats of 39 weeks of age compared to young animals (13 weeks), followed by a dimunition in the 53 weeks old group. In this situation, the content of hepatic GSH and total GSH equivalents as well as the GSH/GSSG ratio were decreased with ageing, while GSSG levels were enhanced in the oldest group studied. Acute ethanol intoxication resulted in a marked increase in liver TBAR content in young animals, together with a decline in GSH, total GSH equivalents and GSH/GSSG ratio, and an enhancement in GSSG.

Antioxidant capacity of desferrioxamine in biological systems.

The antioxidant capacity of desferrioxamine (DF) was investigated in three biological systems. The addition of DF to rat brain homogenates undergoing autoxidation elicited a concentration dependent inhibition of both oxygen uptake and chemiluminescence, with a median inhibitory concentration (IC50) of 0.52 microM.

Dose-dependent study of the effects of acute lindane administration on rat liver superoxide anion production, antioxidant enzyme activities and lipid peroxidation.

The administration of single i.p. doses of lindane (20, 40, 60 and 80 mg/kg) to rats produced a progressive increase in the liver microsomal content of cytochrome P-450 and in the rate of superoxide anion generation, as measured by adrenochrome formation.

Effect of ethanol, acetaldehyde and acetate on the antioxidant-sensitive respiration in the perfused rat liver: influence of fasting and diethylmaleate treatment.

The infusion of 45 mM ethanol or 50 microM acetaldehyde into the perfused rat liver produced comparable and significant antioxidant-sensitive respiratory rates, while marginal responses were obtained with 10 mM acetate. Ethanol-induced antioxidant-sensitive respiration was markedly increased in perfused livers from fasted rats or animals given diethylmaleate which exhibit low hepatic glutathione levels, compared to fed rats. These data point out the significant role of acetaldehyde in ethanol-induced liver oxidative stress, which can be exacerbated by glutathione depletion.

Effects of antioxidants and haemoglobin status on the t-butyl hydroperoxide-induced oxygen uptake by red blood cells.

Oxygen uptake by erythrocytes exposed to t-butyl hydroperoxide (t-BHP) exhibited an induction period. The rate of oxygen consumption can be reduced by antioxidants and blood plasma. The induction time was not appreciably modified by the antioxidants tested, however, plasma increased it by a factor of two.

Visible chemiluminescence from rat brain homogenates undergoing autoxidation. I. Effect of additives and products accumulation.

Rat brain homogenate autoxidation was assessed from thiobarbituric acid reactant accumulation (TBAR), light emission, and oxygen uptake. The effect of several additives upon TBAR accumulation and light intensity suggests that these parameters can be employed as a reliable measure of the lipoperoxidation extent. From the different time profiles of TBAR accumulation and light emission, it is concluded that instantaneous light emission is not a measure of the lipoperoxidation rate but it is related to the accumulation of products.

Superoxide radical generation, NADPH oxidase activity, and cytochrome P-450 content of rat liver microsomal fractions in an experimental hyperthyroid state: relation to lipid peroxidation.

The effect of thyroid hormone treatment on hepatic microsomal functions related to NADPH-dependent electron transfer reactions was studied in rats given 0.1 mg T3/kg BW for 1, 2, 3, and 7 consecutive days. This treatment resulted in increased rates of O2-.

Effect of ethanol and iron on the hepatic and biliary levels of glutathione and lipid peroxidative indexes.

Data presented here indicate that iron exposure exacerbates the changes in the glutathione status of the liver cell and the lipid peroxidative response of the tissue induced by acute ethanol intoxication. In these conditions, additivity in lipid peroxidation was found to occur either when the process was estimated by hepatic malondialdehyde formation, as well as by measurements of the biliary malondialdehyde release in the anesthetized rat and by the antioxidant-sensitive respiration in the perfused rat liver, procedures which are non-invasive for the tissue.

Differential lipid peroxidative response of rat liver and lung tissues to glutathione depletion induced in vivo by diethyl maleate: effect of the antioxidant flavonoid (+)-cyanidanol-3.

The administration of a single dose of diethyl maleate (DEM) to fed rats elicited a drastic decrease in the content of reduced glutathione (GSH) both in liver and lung tissues after 6 h of treatment. Cellular GSH depletion induced by DEM was accompanied by a marked increase in pulmonary lipid peroxidation which was completely abolished by (+)-cyanidanol-3, without changes in the liver. Superoxide dismutase (SOD) activity remained unchanged in both tissues in this situation.