Acute exposure to cobalt induces transient methemoglobinuria in rats.
We observed transient excretion of dark-brown urine after acute exposure to cobalt in rats and investigated the mechanism of it. We injected cobalt into rats s.c. at a dose of 15 mg/kg and collected urine, peripheral blood, and organ samples at the indicated times after injection. Biochemical and histopathological examinations of these samples were conducted. Obvious macroscopic and biochemical methemoglobinuria was observed just after injection of cobalt, but the level of urinary methemoglobin decreased gradually, almost disappearing by 24 h. The levels of cobalt in peripheral blood and urine showed a very similar pattern to that of methemoglobinuria. Neither anemia nor bilirubinemia was observed, indicating no extrarenal intravascular hemolysis. Pathological examination of the kidneys revealed that the glomerular capillaries were filled with red blood cells at 1 h after injection. Electron microscopy showed deformed red blood cells in the glomerular capillaries and condensed hemoglobin in Bowman's capsule that passed through the basement membrane. There were no trends toward increases in plasma levels of creatinine or blood urea nitrogen. These results indicate that exposure to cobalt induces transient methemoglobinuria through the lysis of red blood cells and oxidation of iron in hemoglobin at the glomerular capillaries without causing renal dysfunction.
Horiguchi
Hyogo
H
Department of Health Science, Division of Environmental Immunology and Toxicology, Jichi Medical School, 3311-1 Yakushiji, Minami-Kawachimachi, Kawachi-Gun, Tochigi 329-0498, Japan. hhyogo@jichi.ac.jp
Oguma
Etsuko
E
Nomoto
Satoshi
S
Arao
Yukitomo
Y
Ikeda
Kazuhiro
K
Kayama
Fujio
F
D000818:Animals; D003035:Cobalt / Q000633:toxicity*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects*; D007501:Iron / Q000378:metabolism; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects; D008706:Methemoglobin / Q000652:urine*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D006454:Hemoglobins; D003035:Cobalt; D008706:Methemoglobin; D007501:Iron