Heme oxygenase induction |
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Authors: | Barbara Fulton Elizabeth H Jeffery |
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Institution: | 1. Division of Nutritional Sciences and Institute for Environmental Studies, University of Illinois, 61801, Urbana, IL
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Abstract: | 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. |
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Keywords: | Index Entries" target="_blank">Index Entries Aluminum anemia heme oxygenase mice cytochrome P450 hemoglobin hematocrit |
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