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Open AccessArticle

Extracellular Hb Enhances Cardiac Toxicity in Endotoxemic Guinea Pigs: Protective Role of Haptoglobin

Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA
Division of Internal Medicine, University Hospital, CH-8091 Zurich, Switzerland
Author to whom correspondence should be addressed.
Toxins 2014, 6(4), 1244-1259;
Received: 31 January 2014 / Revised: 18 March 2014 / Accepted: 21 March 2014 / Published: 31 March 2014
(This article belongs to the Collection Toxicity and Therapeutic Interventions in the Immune System)
Endotoxemia plays a major causative role in the myocardial injury and dysfunction associated with sepsis. Extracellular hemoglobin (Hb) has been shown to enhance the pathophysiology of endotoxemia. In the present study, we examined the myocardial pathophysiology in guinea pigs infused with lipopolysaccharide (LPS), a Gram-negative bacterial endotoxin, and purified Hb. We also examined whether the administration of the Hb scavenger haptoglobin (Hp) could protect against the effects observed. Here, we show that Hb infusion following LPS administration, but not either insult alone, increased myocardial iron deposition, heme oxygenase-1 expression, phagocyte activation and infiltration, as well as oxidative DNA damage and apoptosis assessed by 8-hydroxy-2'-deoxyguanosine (8-OHdG) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) immunostaining, respectively. Co-administration of Hp significantly attenuated the myocardial events induced by the combination of LPS and Hb. These findings may have relevant therapeutic implications for the management of sepsis during concomitant disease or clinical interventions associated with the increased co-exposures to LPS and Hb, such as trauma, surgery or massive blood transfusions. View Full-Text
Keywords: hemoglobin; endothelium; endotoxin; haptoglobin; myocardial injury hemoglobin; endothelium; endotoxin; haptoglobin; myocardial injury
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Baek, J.H.; Zhang, X.; Williams, M.C.; Schaer, D.J.; Buehler, P.W.; D'Agnillo, F. Extracellular Hb Enhances Cardiac Toxicity in Endotoxemic Guinea Pigs: Protective Role of Haptoglobin. Toxins 2014, 6, 1244-1259.

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