Oxidant and 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 indicated that asbestos fibres generate reactive oxygen and nitrogen species and cause oxidation and/or nitrosylation of proteins and deoxyribonucleic acid as a marker of cell injury. These effects are potentiated by the inflammation caused by the fibres. Recent studies have shown that individual variability in the antioxidant and/or detoxifying mechanisms probably has an important role in the development of asbestos-related lung diseases. Asbestos fibres 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 nuclear factor kappa B, which has been shown to lead to the upregulation of antioxidant enzymes, most importantly manganese superoxide dismutase. This enzyme is also overexpressed in asbestos-related human malignant mesothelioma, whereas the induction of other antioxidant enzymes (copper-zinc superoxide dismutase, catalase, glutathione peroxidase) by asbestos fibres appears to 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 mechanisms in the human lung provides a basis for future therapies for asbestos-related diseases.