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Antioxid Redox Signal 2010 Feb;12(2):199-208

Differential induction of renal heme oxygenase and ferritin in ascorbate and non-ascorbate producing species transfused with modified cell-free hemoglobin.

Butt OI, Buehler PW, D'Agnillo F


Heme catabolism and iron sequestration systems play an important role in regulating the response to extracellular hemoglobin (Hb). We previously reported that extracellular Hb oxidizes more readily in the circulation of guinea pigs, a non-ascorbate (AA)-producing species with similar plasma and tissue antioxidant status to humans, compared to rats, an AA-producing species. To determine whether these two species exhibit differences in heme catabolism and iron sequestration at the level of the kidney, we examined heme oxygenase (HO), H- and L-ferritin expression, non-heme iron deposition, and renal AA content following transfusion with polymerized bovine hemoglobin (HbG). Both species showed similar rates of hemoglobinuria but urinary HbG was significantly more oxidized in guinea pigs. HbG enhanced HO activity in both species but appeared greater and more sustained in guinea pigs. Conversely, rats showed a greater and more rapid induction of H- and L-ferritin as well as greater iron accumulation and AA content. Furthermore, ferrous and ferric iron deposits were detected in rats while only ferric iron was observed in guinea pigs. These findings suggest significant differences in the renal handling of HbG which may be important for understanding how endogenous antioxidant defenses may modulate the renal response to extracellular Hb.

Category: Journal Article
PubMed ID: #19659432 DOI: 10.1089/ars.2009.2798
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29