Intracellular effects of chronic arsenic administration on renal proximal tubule cells

Arsenic is one of the more common toxic elements in the environment. The kidney accumulates this element and plays a major role in its metabolism and excretion. Mitochondria have been found in vitro to be highly sensitive to the toxicity of this element. Combined oxygen electrode and electron microscopic studies were conducted on kidneys of rats exposed to arsenate in the drinking water at concentrations of 40, 85, or 125 ppm for 6 weeks to evaluate in vivo mitochondrial toxicity. Decreased state 3 respiration and respiratory control ratios were observed in kidneys of rats given the 85 and 125 ppm dose levels. Ultrastructural alterations, which consisted of swollen mitochondria and increased numbers of dense autophagic lysosome-like bodies, were confined to proximal tubule cells of these same animals. This study places renal arsenate mitochondrial toxicity into an in vivo context and points to the value of using complementary techniques for assessing the subacute or chronic toxicity of environmental agents.