Heme oxygenase induction. A possible factor in aluminum-associated anemia.
The effect of repeated parenteral administration of aluminum (Al) was investigated to determine if a relationship exists between the severity of anemia and increase in hepatic heme oxygenase activity. Female Swiss Webster mice were dosed for 11 d with 50 mg Al/kg, as Al lactate, and sodium lactate was given to control mice. On d 12, hematocrit, hemoglobin, blood smears, hepatic heme oxygenase activity, and cytochrome P450 levels were assessed. Significant decreases in hematocrit (39.1 +/- 0.7 vs 43.1 +/- 0.3% in controls) and hemoglobin (13.1 +/- 0.4 vs 14.2 +/- 0.2 g/dL in controls) were produced by Al administration. Blood smears from Al-treated mice consistently showed smaller, more irregular red cells. Cytochrome P450 content was significantly decreased (0.443 +/- 0.043 vs 0.665 +/- 0.055 nmol/mg) whereas hepatic heme oxygenase activity was significantly increased (2.75 +/- 0.34 vs 1.66 +/- 0.20 nmol/mg/h) in Al-treated animals. The production of mild anemia by parenteral aluminum correlated significantly with the increase in heme oxygenase activity, which, although only 66% greater than in control, preceded a significant loss of cytochrome P450. The increased heme oxygenase activity, with subsequent increased destruction of heme and/or heme proteins is discussed as a possible mechanism for the microcytic, hypochromic anemia associated with Al overload.
Fulton
B
B
Division of Nutritional Sciences, University of Illinois, Urbana 61801.
Jeffery
E H
EH
D000535:Aluminum / Q000008:administration & dosage / Q000633:toxicity*; D000747:Anemia, Hypochromic / Q000139:chemically induced* / Q000201:enzymology; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004790:Enzyme Induction; D005260:Female; D006400:Hematocrit; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D006454:Hemoglobins / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D051379:Mice
D006454:Hemoglobins; D003577:Cytochrome P-450 Enzyme System; D000535:Aluminum; D006419:Heme Oxygenase (Decyclizing)