Mairam Gulumian

Hydroxyl radical production in the presence of fibres by a Fenton-type reaction

Glass fibres are considered to be inert and therefore thought to present no real hazard to the health of people who inhale them. Results in the present study however indicate that these fibres are able to produce hydroxyl radicals in the presence of hydrogen peroxide by a Fenton-type reaction. Since hydroxyl radical is implicated in lipid peroxidation, single-strand DNA breaks and carcinogenesis, care should be exercised when dealing with glass fibres.

Lipid peroxidation in microsomes induced by crocidolite fibres

When rat liver and lung microsomes were incubated with crocidolite fibres, a substantial increase in lipid peroxidation was observed. Increasing concentrations of this fibre in the incubation mixture, produced a concomitant induction in microsomal lipid peroxidation. This increase was very rapid as the reaction was almost complete within 10 min. The ability of these fibres to induce this process after a short period of incubation seems to be due to their binding to the microsomes. The iron present in the structure of crocidolite is thought to be responsible for catalysing the peroxidation. The formation of free radicals by asbestos and possible pathological sequelae are discussed.

Lipid peroxidation and trace elements in systemic sclerosis.

Oxidative stress appears to be important in the causation and perpetuation of tissue injury and fibrosis in systemic sclerosis or scleroderma (SSc). We conducted a case-control study to assess lipid peroxidation levels as determined by measuring fasting plasma malondialdehyde (MDA) and serum levels of the trace elements selenium, iron, zinc and copper in SSc. Plasma MDA levels were almost tenfold higher in patients than in controls (p=0.00007), and an inverse relationship between MDA levels and disease duration (r=–0.52, p=0.044) was observed. Selenium levels were lower in patients than in controls (p=0.012). Within the patient cohort, copper correlated inversely with the total skin score (r=–0.52, p=0.03). Our findings provide further evidence that lipid peroxidation is increased and antioxidant capacity is reduced in SSc. The gradual decline in MDA levels with time suggests that antioxidant therapy, if to be useful in SSc, is most likely to be effective early in the course of the disease.

Crocidolite-induced lipid peroxidation in rat lung microsomes: I. Role of different ions

Lipid peroxidation is increased by ferrous or ferric ions in rat lung microsomes both from rats pretreated with 3-methylcholanthrene and from untreated controls. This increase was dependent on the concentration of these ions in the reaction mixture. Crocidolite alone increased peroxidation in microsomal fractions. However, addition of ferric or ferrous ions with the crocidolite did not give a greater increase in the amount of peroxidation in microsomes. Chelation with EDTA of iron, whether originally present as free ions in the solution or attached to crocidolite, prevented lipid peroxidation. NADPH alone, when added to the microsomal fractions, did not produce any significant effect. However, when added concomitantly with crocidolite fibers, NADPH reduced the effect of crocidolite on lipid peroxidation. Magnesium, manganese, and calcium ions did not produce any significant effect on lipid peroxidation in the presence or absence of crocidolite. A reduced pH enhanced the rate of lipid peroxidation in line with increased solubility of iron salts at these pH values. All the above observations, taken together, lead to the conclusion that it is the iron in the crocidolite that is responsible for the latters ability to enhance lipid peroxidation.

Crocidolite-induced lipid peroxidation: II. Role of antioxidants

Asbestos fibers in vitro produce lipid peroxidation in rat lung microsomes. Butylated hydroxytoluene prevented this peroxidation. Ascorbate in low concentrations enhanced peroxidation of lipids but inhibited it at concentrations above 4 mmole/liter so that it partially protected membrane lipids from peroxidation produced by asbestos fibers. Reduced glutathione added to microsomes gave increased peroxidation at increased concentrations up to 20 mmol/liter. At 40 mmol/liter peroxidation was prevented. Glutathione had no obvious effect on the level of peroxidation produced by asbestos fibers. The 105,000g supernatant cell fraction added either with or without glutathione gave a decrease in the amount of lipid peroxidation produced by asbestos fibers. The protective action of these reducing agents suggests a possible use as prophylactic agents against the harmful effects of inhaled asbestos.

ESR and Mössbauer studies on detoxified crocidolite: Mechanism of reduced toxicity

Abstract A process for the detoxification of crocidolite fibers was previously reported in the literature. The fibers of this mineral asbestiform were treated with ferric oxide salts to form a metal-micelle polymer surface coating which prevented physiological reactions with the mineral. In the present study, detoxified crocidolite was tested for its ability to generate hydroxyl radicals in the presence of hydrogen peroxide; the intensity of the electron spin resonance signal was less than that produced by the native toxic crocidolite fibers. Similar experiments showed that the ability of the detoxified crocidolite to reduce oxygen was also decreased compared with the native crocidolite. The availability of ferrous iron present in the two crocidolite fibers to catalyze the above reactions was investigated with the chelating agent ferrozine. The results indicate that ferrozine was able to mobilize fewer ferrous ions from detoxified crocidolite compared with the native crocidolite. Moreover, Mossbauer-effect spectroscopy studies have shown that the detoxification process results in both bulk and surface changes of the crystal-chemistry of the detoxified sample. This detoxification process also introduces a surface coating comprising ferric ions which shield near-surface ferrous irons and consequently reduces the Fenton-type reactivity of the fibers. It is therefore inferred from this combination of techniques that the ability of the crocidolite fibers to generate oxygen-centered radicals is dependent on the iron redox state and its chelation to different molecules. This in turn, may have an important effect on the ability of the fibers to exert their toxicity.

Bulk and surface modifications in detoxified crocidolite

Crocidolite is a fibrous mineral asbestiform which is widely used in industry. The fibers of this material have a high electron donor capability. This promotes electrostatic repulsion between the fibers and they are readily dispersed into the atmosphere. Airborne fibers are eventually inhaled into the lungs where they induce carcinoma and mesothelioma. Therefore much effort has been directed towards moderating the toxicity of crocidolite and related mineral asbestiforms. One detoxifying procedure has involved coating crocidolite fibers with an iron complex. In the present study, Mossbauer-effect spectroscopy has been used to monitor any crystal and chemical modifications that have occurred after this detoxification process has been applied. An analysis of the Mossbauer data has shown that the detoxification process 1) induces a change of valence at some of the bulk ferrous ion sites and 2) produces a ferric-base surface complex. There is therefore a concomitant modification of electron donor characteristics of the fibers. Experimental evidence has been presented which suggests that the coating applied in the detoxification process is a chemical complex of the form [Fe(H2O)6]3+. The nature and location of this complex may help to inhibit surface Fenton-type reactions and may consequently moderate the toxicity of the fibers.

Detoxified Crocidolite Exhibits Reduced Radical Generation which could Explain its Lower Toxicity: ESR and Mossbauer Studies

Asbestos fibres are widely used commercially because of their insulating and friction properties. Exposure to these fibres however can produce asbestosis and cancer of the lung and mesothelium. Attempts have therefore been made to detoxify these fibres to reduce their biological toxicity but retain their desirable characteristics. One such attempt was reported by Flowers (1982). The procedure involved exposure of fibres to ferric ammonium sulfate for 30 min and then the addition of ammonium hydroxide. This modified the surface of the fibres by metal oxides to a metal micelle form of asbestos. This treatment preserved the commercial properties of the fibres but reduced their toxicity to human lung macrophages and decreased the hemolytic activity to red blood cells (Hahon et al. 1986).

An investigation of the mechanism of detoxification in asbestos

Abstract57Fe Mössbauer effect spectroscopy studies were conducted on native crocidolite and on a sample which had been detoxified by means of a chemical treatment with ferric salts. This allows for a comparison between the crystal chemistry of the untreated and treated samples. Significant chemical changes in the treated sample have been inferred from the Fe site-population analysis after conducting a temperature-dependent study of both samples in the range 300 K down to 90 K. These results, together with the results from complementary Electron Spin Resonance (ESR) studies, may help to elucidate the mechanism of toxicity in these asbetiforms.

Oxygen Consumption, Lipid Peroxidation and Mineral Fibres

Asbestos-induced lipid peroxidation in different systems is well documented in the literature. Many reports note the detection of malondialdehyde as a measure of peroxidation of unsaturated fatty acids by the thiobarbituric acid (TBA) method. Although the TBA method is quite simple and easy to use, it has many limitations and therefore has to be cross-checked by reference to one or more other methods.