• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Scientific Publications by FDA Staff

  • Print
  • Share
  • E-mail

Search Publications



Starting Date

Ending Date

Order by

Entry Details

Toxicology 2018 Jun 1;402-3:37-49

Reversible Renal Glomerular Dysfunction in Guinea Pigs Exposed to Glutaraldehyde-Polymerized Cell-Free Hemoglobin.

D'Agnillo F


Chemically modified hemoglobin (Hb)-based oxygen carriers are promising oxygen replacement therapeutics however their potential renal effects are not fully understood. Using a guinea pig exchange transfusion model, we examined the effects of glutaraldehyde-polymerized bovine hemoglobin (HbG) on the permeability and integrity of the glomerular filtration barrier (GFB), which is comprised of podocytes, fenestrated endothelium, and the glomerular basement membrane. HbG induced marked proteinuria characterized in part by the loss of high molecular weight proteins, including albumin, immunoglobulin, and transferrin, at 4 and 12¿hours post-infusion that resolved by 72¿hours. This correlated with HbG-induced GFB alterations based on the reduced expression of specific markers of podocytes (podocin, nephrin, podocalyxin, and Wilms Tumor 1 protein) and endothelial cells (ETS-related gene and claudin-5). Lectin binding studies also demonstrated marked but reversible alterations to the GFB glycocalyx accompanied by increased intraglomerular HbG deposition and 4-HNE protein adduct expression indicative of oxidative damage. Together, these findings indicate that HbG induces reversible glomerular barrier dysfunction in conjunction with transient GFB changes providing new insight into the renal response to chemically modified Hb therapeutics.

Category: Journal Article
PubMed ID: #29689364 DOI: 10.1016/j.tox.2018.04.005
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2018-02-11 Entry Last Modified: 2019-06-09