Human Albumin Improves Endothelial Dysfunction and Survival in Experimental Endotoxemia Model

In an experiment to better understand the mechanisms by which human albumin might protect against sepsis-induced organ dysfunction and improve survival, French scientists injected three groups of Swiss mice with lipopolysaccharide (LPS) followed by 10 mL/kg of 4% human albumin, 10 mL/kg of 20% human albumin or 30 mL/kg of normal saline. Separately, human uterine vein endothelial cells were exposed to both LPS and tumor necrosis factor-α (TNF-α) for eight hours in the presence or absence of 4% or 20% albumin.

Endotoxemic mice infused with 4% albumin, but not 20% albumin or normal saline solution, experienced an improved average survival time.The 4% albumin treatment also 1) activated endothelial nitric oxide synthase, 2) restored LPS-impaired flowdependent endothelial dilation in mesenteric arteries, 3) reduced LPS-induced renal dysfunction and 4) enhanced endothelin-1 production and glutathione plasma levels. In the uterine vein model, 4% albumin but not 20% albumin blunted LPS-TNF-αinduced oxidative and nitrosative stresses in endothelial cells and increased their glutathione levels.

“The present data confirm a protective effect of 4% human serum albumin both on [mouse] survival and endothelial dysfunction by inhibiting inflammatory and oxidative stress pathways induced by endotoxins,” the investigators concluded. “Conversely, higher [albumin] concentrations were detrimental, suggesting a dose-dependent effect.”