The role of transforming growth factor-ß1 and oxidative stress in podoconiosis pathogenesis

Background. Podoconiosis (endemic non-filarial elephantiasis) occurs in susceptible individuals who go barefoot in regions of irritant volcanic soil. Silicate particles absorbed via the skin are thought to induce an inflammatory process and a consequent endolymphangitis of the lower leg lymphatics. Objectives. To establish which oxidative stress biomarkers play a part in the inflammatory process, and to test whether TGF-1 also has a pathogenetic role. Patients/Methods. We enrolled 50 early clinical stage patients, 43 advanced stage patients and 35 local healthy controls. Oxidative stress biomarkers included serum total peroxides (TP), total antioxidant capacity (TAC), total nitrate plus nitrite (TN), malondialdehyde (MDA) and total superoxide dismutase (SOD) activity. Serum total TGF-1 was assayed using sandwich ELISA assay. Results. Compared with healthy controls, early stage patients showed significantly higher mean levels of TP (p<0.001), MDA (p<0.05), and OSI (p<0.01); and significantly lower mean concentrations of SOD (p<0.001) and TGF-1 (p<0.001). Mean levels of TGF-1 were even lower among advanced stage patients (p<0.001). Mean TAC levels were significantly lower among patients with advanced disease than either other group (p<0.001). Conclusions. This is the first study to attempt to elucidate the molecular pathogenetic events in podoconiosis. We conclude that TGF-1 may have a pathogenetic role, with oxidative stress playing a minor role in the early stages of disease.