Structural alterations in the rat kidney after acute arsine exposure.
The mechanism of arsine (AsH3) toxicity is not completely understood. In this investigation, the toxicity of AsH3 and AsH3-produced hemolytic products was determined in primary culture of renal cortical epithelial cells and in the in situ isolated rat kidney. The objective of this study was to model kidney dysfunction caused by AsH3 exposure. The hypothesis was that unchanged AsH3 and AsH3-produced hemolysate that may contain arsenite (As(III)) as metabolite are both responsible for renal toxicity. Toxicity in isolated cells was determined by 2, 3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxa nilide inner salt (XTT) bioreduction, intracellular potassium (K+), and lactate dehydrogenase (LDH) leakage. Data from XTT bioreduction showed that most toxicity occurred at 1 hour and was independent of the arsenic species. At 4 hours, the observed toxicity depended on the arsenic species and was generated by As(III). In the isolated cells, the As(III)-spiked hemolysate produced similar toxicities with regard to intracellular K and 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 exposure to AsH3, the effects of toxicity were observed mainly in the glomerular and peritubular endothelial cells. Tubular epithelial cells also presented early signs of toxicity. The AsH3-hemolysate was not toxic after a 1 -minute exposure. These data suggested that early cytotoxicity caused by unchanged AsH3 results in kidney dysfunction, produced by AsH3, and later by the formation of a hemolysate that may contain As(III). These data may be important in understanding the renal toxic effects after AsH3 intoxication.
Ayala-Fierro
F
F
Department of Pharmacology and Toxicology, College of Pharmacy, Center for Toxicology, University of Arizona, Tucson 85721, USA. ayala@pharmacy.arizona.edu
Baldwin
A L
AL
Wilson
L M
LM
Valeski
J E
JE
Carter
D E
DE
D000818:Animals; D001152:Arsenicals / Q000494:pharmacology*; D002478:Cells, Cultured; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017207:Rats, Sprague-Dawley
D001152:Arsenicals; C006633:arsine