**5. Reactive oxygen and nitric species: the link between asbestos exposure and the development of asbestosis**

The pathogenesis of asbestosis is still poorly understood. The findings of studies on cell cultures and animal models indicate that reactive oxygen and nitric species (ROS and RNS) are involved in the pathogenesis of this disease [23, 30, 45–55]. The most important reactive metabolites in the pathogenesis of asbestos-related lung diseases are superoxide anion (O2 − ), hydrogen peroxide (H2O2), hydroxyl radical (OH˙) and nitric oxide (NO) [46, 48, 56, 57]. Asbestos may stimulate the production of ROS in two different ways. The first mechanism involves redox-active iron (Fe2+, Fe3+) in asbestos that catalyses the formation of OH˙, whereas the second mechanism involves the production of ROS by alveolar macrophages during the phagocytosis of asbestos fibres [58–60]. Reactive oxygen species in lungs may lead to the production of cytotoxic and potentially genotoxic electrophilic compounds [46].

It has also been suggested that asbestos fibres may upregulate the activity of inducible nitric oxide synthase (iNOS), thus inducing the production of NO by alveolar macrophages and pulmonary epithelial cells [51, 61–64]. Because NO is a free radical, it reacts readily with other reactive oxygen metabolites (as, for instance, O2 − ), leading to the formation of toxic metabolites, most importantly peroxynitrite [65–69]. Nitric oxide may play a role in the initiation and progression of asbestosis [51, 64, 70, 71]. However, the data presented by Dörger et al. [72] indicate that iNOS-derived NO plays a dual role in acute asbestos-induced lung injury and that although iNOS deficiency resulted in an exacerbated inflammatory response, it improved oxidant-promoted lung tissue damage.

Reactive oxygen species and RNS can damage all types of biomolecule, including lipids, proteins and deoxyribonucleic acid (DNA). Complex defence mechanisms, including enzymes, proteins and antioxidants, are involved in the prevention of cell damage [73, 74].
