Haptoglobin reduces renal oxidative DNA and tissue damage during phenylhydrazine-induced hemolysis.
BACKGROUND
Haptoglobin knockout (Hp-/-) mice are more sensitive to phenylhydrazine-induced hemolysis than Hp+/+ mice.


METHODS
Hemolysis was induced in Hp-/- and Hp+/+ mice using phenylhydrazine. Relative renal tissue damage and function were then assessed.


RESULTS
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.


CONCLUSIONS
Haptoglobin appears to play an important physiological role as an antioxidant, particularly during hemolysis.
Lim
Y K
YK
National University Medical Institutes, The National University of Singapore.
Jenner
A
A
Ali
A B
AB
Wang
Y
Y
Hsu
S I
SI
Chong
S M
SM
Baumman
H
H
Halliwell
B
B
Lim
S K
SK
D000210:Acute-Phase Reaction / Q000139:chemically induced / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004921:Erythropoietin / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006242:Haptoglobins / Q000235:genetics* / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D051547:Heme Oxygenase-1; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects / Q000502:physiology*; D007444:Inulin / Q000493:pharmacokinetics; D007668:Kidney / Q000378:metabolism*; D007677:Kidney Function Tests; D015227:Lipid Peroxidation / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D010659:Phenylhydrazines / Q000633:toxicity; D014316:Tritium
D000447:Aldehydes; D000975:Antioxidants; D006242:Haptoglobins; D006454:Hemoglobins; D008565:Membrane Proteins; D010659:Phenylhydrazines; C030299:phenylhydrazine; D014316:Tritium; D004921:Erythropoietin; D008315:Malondialdehyde; C024829:8-hydroxyguanine; D006147:Guanine; D007444:Inulin; D004247:DNA; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C027576:4-hydroxy-2-nonenal