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- Title
Haptoglobin reduces renal oxidative DNA and tissue damage during phenylhydrazine-induced hemolysis.
- Authors
Lim, Yew Koon; Jenner, Andrew; Ali, Azhar Bin; Wang, Yanping; Hsu, Stephen I-Hong; Chong, Siew Meng; Baumman, Heinz; Halliwell, Barry; Lim, Sai-Kiang; Lim, Y K; Jenner, A; Ali, A B; Wang, Y; Hsu, S I; Chong, S M; Baumman, H; Halliwell, B; Lim, S K
- Abstract
<bold>Background: </bold>Haptoglobin knockout (Hp-/-) mice are more sensitive to phenylhydrazine-induced hemolysis than Hp+/+ mice.<bold>Methods: </bold>Hemolysis was induced in Hp-/- and Hp+/+ mice using phenylhydrazine. Relative renal tissue damage and function were then assessed.<bold>Results: </bold>Hp-/- mice had higher basal levels of renal lipid peroxidation, as evidenced by levels of malonaldehyde and 4-hydroxy-2(E)-nonenal (MDA/HNE). After the administration of phenylhydrazine, levels of 8-hydroxyguanine (but not other products of oxidative DNA damage) were significantly elevated in the renal DNA. There was also increased induction of heme oxygenase-1. The more severe renal damage in Hp-/- mice was also evident in the delayed erythropoietin gene expression and poorer renal clearance of 3H-inulin. This reduction in glomerular filtration function in Hp+/+ and Hp-/- mice could be restored to baseline by vasodilators (prazosin or diazoxide), implicating renal vasoconstriction as a major mechanism of acute renal failure during induced hemolysis. Precipitation of hemoglobin in the kidney was not increased in Hp-/- mice.<bold>Conclusions: </bold>Haptoglobin appears to play an important physiological role as an antioxidant, particularly during hemolysis.
- Subjects
HAPTOGLOBINS; DNA; PHENYLHYDRAZINE
- Publication
Kidney International, 2000, Vol 58, Issue 3, p1033
- ISSN
0085-2538
- Publication type
journal article
- DOI
10.1046/j.1523-1755.2000.00261.x