The role of transforming growth factor-beta1 and oxidative stress in podoconiosis pathogenesis.

Abstract

Podoconiosis (endemic nonfilarial 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. To establish which oxidative stress biomarkers play a part in the inflammatory process, and to test whether transforming growth factor (TGF)-beta1 also has a pathogenetic role. We enrolled 50 patients with early clinical stage disease, 43 patients with advanced stage disease 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. The oxidative stress index (OSI) was also determined. Serum total TGF-beta1 was assayed using sandwich enzyme-linked immunosorbent assay. Compared with healthy controls, patients with early stage disease 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-beta1 (P < 0.001). Mean levels of TGF-beta1 were even lower among patients with advanced stage disease (P < 0.001). Mean TAC levels were significantly lower among patients with advanced disease than either other group (P < 0.001). This is the first study, to our knowledge, to attempt to elucidate the molecular pathogenetic events in podoconiosis. We conclude that TGF-beta1 may have a pathogenetic role, with oxidative stress playing a minor role in the early stages of disease.