Oxidant sand antioxidant mechanisms of lung disease caused by asbestos fibres

The pathogenesis of asbestos-related lung diseases is complicated and still poorly understood. Studies on animal models and cell cultures have indicat ed that asbestos fibres generate reactive oxygen and nitrogen species and c ause oxidation and/or nitrosylation of proteins and deoxyribonucleic acid a s a marker of cell injury. These effects are potentiated by the inflammatio n caused by the fibres. Recent studies have shown that individual variabili ty in the antioxidant and/or detoxifying mechanisms probably has an importa nt role in the development of asbestos-related lung diseases. Asbestos fibr es cause both cell proliferation and apoptosis by multiple mechanisms, one of them being activation of signal transduction pathways by reactive oxygen and nitrogen species. Asbestos activates transcription factors such as nuc lear factor kappa B, which has been shown to lead to the upregulation of an tioxidant enzymes, most importantly manganese superoxide dismutase. This en zyme is also overexpressed in asbestos-related human malignant mesothelioma , whereas the induction of other antioxidant enzymes (copper-zinc superoxid e dismutase, catalase, glutathione peroxidase) by asbestos fibres appears t o be marginal. The significance of antioxidant enzymes in asbestos related diseases has, however, remained unclear. Furthermore, previous studies have not been able to offer successful therapies to the patients with asbestos- associated diseases. Only an improved understanding of the pathogenetic mec hanisms in the human lung provides a basis for future therapies for asbesto s-related diseases.