Effects of cadmium chromium and mercury alone and in combination of lung tussue of Sprague-Dawley rats

Abstract

Heavy metals are widely used in numerous applications and enviromental exposure has increased. The prevalence of respiratory disease worldwide has also increased dramatically and research has linked heavy metal exposure via inhalation to diseases of the respiratory system, particularly pulmonary fibrosis. The lungs are often overlooked when the toxicity of heavy metals after oral exposure is being investigated. Enviromental exposure is not limited to a single metal but as part of mixtures of metals. In the South African milieu cadmium, chromium and mercury are common metal contaminants in water. Therefore, the aim of this study was to investigate the effects of exposure to 1000 times the World Health Organization’s limits of cadmium, chromium and mercury alone and in combination on the lung tissue of Sprague-Dawley rats. Sprague-Dawley rats (6 rats per group including controls) were daily orally gavaged with dosages equivalent to a 1000 times, the World Heatlh Organisation’s limits for cadmium, chromium and mecruy alone and in combinations (Cd, Cr , Hg, Cd + Cr, Cd + Hg, Cr + Hg and Cd + Cr + Hg) for 28 days. After exposure the controls and exposed rats were terminated and the tissue and cellular structure of the bronchioles and lungs were evaluated. Tissue structure was evaluated using specific stains. Transmission electron microscopy was used to evaluate the ultrastructural changes in type I and II alveolar cells as well as the distribution of collagen and elastic fibers. In the exposed groups, thickening of the intra-alveolar space, desquamation of epithelial cells of the bronchioles with increase in cellular debris was observed. Additionally, the presence of bronchus-assoicated lymphoid tissue was observed, with increased displacement and distribution of collagen type III to type I. Elastin fibres appeared more fragmented along the basement membrane of the exposed groups compared to the control. Ultrastructural analyses revealed the detachment of the nuclear membrane of alveolar type II cells, with a prominent increase in collagen and elastin bundles and the presence of mast cells near injured alveolar type II cells. Mercury alone and the combinations containing mercury, (Cr + Hg, Cd + Hg and Cd + Cr + Hg) were the most toxic. In conclusion, this study identified, that following oral exposure to metals such as cadmium, chromium and mercury, the lungs are a specific target of toxicity. Therefore, in addition to aerosol heavy metal exposure, oral exposure can also contribute to lung damage and the development of lung fibrosis.