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.
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.
Authors: Sharmila Fagoonee; Jakub Gburek; Emilio Hirsch; Samuele Marro; Soren K Moestrup; Jacob M Laurberg; Erik I Christensen; Lorenzo Silengo; Fiorella Altruda; Emanuela Tolosano Journal: Am J Pathol Date: 2005-04 Impact factor: 4.307
Authors: Kristin M Huntoon; Lisa Russell; Erin Tracy; Karen W Barbour; Qingsheng Li; Protul A Shrikant; Franklin G Berger; Lee Ann Garrett-Sinha; Heinz Baumann Journal: Mol Immunol Date: 2013-03-30 Impact factor: 4.407
Authors: Patricia A Shi; Erika Choi; Narendranath R Chintagari; Julia Nguyen; Xinhua Guo; Karina Yazdanbakhsh; Narla Mohandas; Abdu I Alayash; Elizabeth A Manci; John D Belcher; Gregory M Vercellotti Journal: Br J Haematol Date: 2016-08-10 Impact factor: 6.998