Structural alterations in the rat kidney after acute arsine exposure

The mechanism of arsine (AsH3) toxicity is not completely understood. In th is investigation, the toxicity of AsH3 and AsH3-produced hemolytic products was determined in primary culture of renal cortical epithelial cells and i n the in situ isolated rat kidney. The objective of this study was to model kidney dysfunction caused by AsH3 exposure. The hypothesis was that unchan ged AsH3 and AsH3-produced hemolysate that may contain arsenite (As(III)) a s metabolite are both responsible for renal toxicity. Toxicity in isolated cells was determined by 2, 3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetraz olium-5-carboxanilide inner salt (XTT) bioreduction, intracellular potassiu m (K+), and lactate dehydrogenase (LDH) leakage. Data from XTT bioreduction showed that most toxicity occurred at 1 hour and was independent of the ar senic species. At 4 hours, the observed toxicity depended on the arsenic sp ecies and was generated by As(III). In the isolated cells, the As(III)-spik ed hemolysate produced similar toxicities with regard to intracellular K+ a nd LDH. The AsH3-hemolysate only affected LDH at 1 hour. Unchanged AsH3 was very toxic to the isolated rat kidney. In this system, after 10 minutes ex posure to AsH3, the effects of toxicity were observed mainly in the glomeru lar and peritubular endothelial cells. Tubular epithelial cells also presen ted early signs of toxicity. The AsH3-hemolysate was not toxic after a 10-m inute exposure. These data suggested that early cytotoxicity caused by unch anged AsH3 results in kidney dysfunction, produced by AsH3 and later by the formation of a hemolysate that may contain As(lll). These data may be impo rtant in understanding the renal toxic effects after AsH3 intoxication.