In vitro tissue specificity for arsine and arsenite toxicity in the rat.
The mechanism of arsine (AsH3) toxicity is not completely understood. In this investigation, we determined AsH3 and arsenite (AsIII) toxicity in Sprague Dawley rat blood, liver, and kidney. In all systems, there were dose- and time-dependent responses. Red blood cells were very susceptible to AsH3 toxicity. This was demonstrated by an immediate intracellular potassium loss and by hemolysis and lactate dehydrogenase (LDH) leakage that occurred by one h. AsIII concentrations up to 1 mM were not toxic to red blood cells using these indicators. Both AsH3 and AsIII produced toxicity in primary hepatocytes. Both produced significant LDH leakage and decreases in intracellular K+ by 5 h, but AsIII was more toxic than AsH3. At 24 h, both arsenic species showed similar toxicity. In renal cortical epithelial cells, AsH3 produced no effects on LDH and K+ over a 5-h period but produced significant LDH leakage by 24 h. In these cells, AsIII produced significant toxicity as early as in 3 h. These results showed that unchanged AsH3 produced toxicity in tissues, in addition to blood, and that toxicity of arsenicals is arsenic species- and tissue-dependent.
Ayala-Fierro
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Department of Pharmacology and Toxicology, College of Pharmacy, Southwest Environmental Health Sciences Center, University of Arizona, Tucson 85721, USA.
Barber
D S
DS
Rael
L T
LT
Carter
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DE
D000395:Air Pollutants, Occupational / Q000009:adverse effects*; D000818:Animals; D001152:Arsenicals / Q000009:adverse effects*; D018053:Arsenites / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000166:cytology / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008297:Male; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley
D000395:Air Pollutants, Occupational; D001152:Arsenicals; D018053:Arsenites; C015001:arsenite; C006633:arsine