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Apo‐hemoglobin and Haptoglobin Limit Acellular Hemoglobin Negative Effects
Author(s) -
Munoz Carlos Jose,
Pires Ivan S.,
Buehler Paul W.,
Palmer Andre F.,
Cabrales Pedro
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.07184
Subject(s) - hemoglobin , haptoglobin , hemopexin , heme , toxicity , pharmacology , medicine , blood substitute , hemolysis , chemistry , biochemistry , enzyme
Background Haptoglobin (Hp), a scavenger protein for hemoglobin, and apo‐hemoglobin (apoHb), a chemically synthesized scavenger protein for free heme, present promise in preventing acellular hemoglobin toxicity. The purification process of both molecules is cost effective and can help a number of patients suffering from a septic shock, thalassemia, sickle cell and various other diseases. Methods Systematic parameters, microhemodynamics and pharmacokinetics were observed on Golden Syrian hamsters (n=32) using intravital microscopy on the dorsal skin fold. Hamsters were injected with apoHb, Hp, and a combination of apoHb and Hp via the carotid artery. This was followed by a single 10% top‐load of acellular Hb via the carotid artery Results A combined treatment with apoHb and Hp was found to reduce acellular hemoglobin toxicities. Systematic parameters and microhemodynamics of all sized arterioles and venules resulted in sustained values when compared to baseline and other treatments (apoHb and Hp alone). The pharmacokinetics data suggests strong scavenging functionality over 6 hours. Conclusion The results suggest a promising treatment against acellular hemoglobin and hemolytic anemia induced toxicity where the apoHb is stabilized in a molar excess of Hp preventing vasoconstriction and preserving microvascular blood velocity and blood flow. Ultimately, these results support the efficacy of using purified Hp and apoHb to control hemoglobin and heme induced toxicity. Support or Funding Information This work was supported by the NIH Heart Lung and Blood Institute under Grants T32‐HL105373, R01‐HL126945, and the DOD DMRDP under Grant W81XWH‐18‐1‐0059