Nephrotoxicity of nickel carbonyl in rats

Urinary excretions of protein and amino acids were measured before and after exposure of rats to inhalation of nickel carbonyl in LD40 dosage. Urinary excretion of total protein was increased by an average of 2.4-fold on the first day after exposure and remained elevated (2.0-fold and 1.9-fold) on the second and third days. Urinary excretions of 16 neutral or basic amino acids were all increased on the third day. In comparison to pre-exposure values, the increased excretion of neutral or basic amino acids averaged 3.0-fold, and ranged from 1.2-fold (ornithine) to 7.3-fold (valine). Among the acidic amino acids and amides, only the excretion of glutamic acid was increased (4.6-fold), and the excretions of glutamine, aspartic acid and asparagine were reduced, respectively, to 3.8 percent, 64 percent, and 52 percent of the pre-exposure values. Urinary excretion of ammonia was greatly increased after exposure to nickel carbonyl. The alterations of urinary excretions of amino acids were apparently mediated by nephrotoxicity rather than by mobilization of amino acids from tissues, since plasma concentrations of amino acids were not significantly affected by exposure to nickel carbonyl. The pronounced diminution of glutamine excretion and the marked increase of ammonia excretion were consistent with enhanced renal production of ammonia from glutamine by action of glutaminase.