Nephrotoxicity of sodium arsenate in dogs.
Nephrotoxicity of sodium arsenate was evaluated in dogs to determine the pathophysiologic basis for renal lesions caused by this heavy metal. Examination of biopsy specimens indicated that the low dose of the As salt (0.73 mg/kg of body weight) produced histologic changes consisting of mild degeneration and vacuolation of renal tubular epithelium. Vacuolation involved mainly the ascending thick portion of the nephron. Clinical pathologic changes were not demonstrable at this dosage level according to glomerular filtration rate (creatinine clearance), fractional reabsorption of sodium, potassium, and chloride; plasma osmolar and free water clearance; and urinalysis. The medium dose (7.33 mg/kg) resulted in alterations determined by urinalysis, but did not markedly affect other clinical pathologic measurements. Histopathologic changes were equal to or greater than those seen with the low dose. Tubular necrosis was observed in the cortical portion of the nephron and the ascending thick limb. The high dose (14.66 mg/kg) consistently produced marked changes in all parameters evaluated. Clinical pathologic alterations were compatible with acute tubular necrosis involving all segments of the nephron. Histologically, moderate glomerular sclerosis and severe tubular necrosis were observed. During recovery from the high dose of As, a gradual compensatory healing process was observed that was evident in all clinical pathologic parameters and was confirmed from sequential renal biopsy specimens.
D000818:Animals; D001149:Arsenates / Q000633:toxicity*; D001151:Arsenic / Q000633:toxicity*; D004283:Dog Diseases / Q000139:chemically induced* / Q000473:pathology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000662:veterinary*; D007677:Kidney Function Tests / Q000662:veterinary; D007678:Kidney Glomerulus / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology
D001149:Arsenates; C009277:sodium arsenate; D001151:Arsenic