Alcohol consumption in rats potentiates the deleterious effect of gram-negative sepsis on hepatic hyaluronan uptake.
The role of hepatic sinusoidal endothelial cells (SECs) in the pathologic changes of the liver associated with alcohol consumption is not fully understood. The measurement of hyaluronan (HA) uptake by the SECs provides a useful means for assessing the functional state of these cells. In this study, we determined the effect of acute and chronic exposure to alcohol in rats in the absence and presence of subcutaneous Escherichia coli-induced sepsis on plasma HA concentration and HA uptake by the isolated, perfused liver. Rats were administered ethanol (two doses of 0.2 g/100 g body weight, intraperitoneally, 24 and 15 hr before killing) or fed a liquid diet for 8-10 weeks, containing alcohol (36% of the total calories) or dextrin (in isocaloric amounts). Twenty-one hr before euthanizing for liver perfusion, animals were injected subcutaneously with live E. coli (sepsis) or sterile saline (control). Neither acute nor chronic alcohol exposure by themselves altered plasma HA levels. However, both treatments exacerbated the hyperhyaluronanemic effect of sepsis. Thus, in acutely alcohol-treated rats, sepsis induced a 187% (p < 0.05) increase in plasma levels of HA, whereas in nonalcohol septic rats, the increase was only 54% (p < 0.05). Likewise, sepsis resulted in a greater increase in the plasma levels of HA (871%) in alcohol-fed rats than it did in liquid diet, control-fed rats (323%, p < 0.05). The rate of HA uptake by the isolated, perfused liver was not altered by either acute or chronic alcohol exposure. However, alcohol exposure markedly potentiated the inhibitory effect of sepsis on the capacity of the liver to take up HA.(ABSTRACT TRUNCATED AT 250 WORDS)
Deaciuc
I V
IV
Department of Physiology, Louisana State University Medical Center, New Orleans 70112-1393.
McDonough
K H
KH
Bagby
G J
GJ
Spitzer
J J
JJ
D000435:Alcoholic Intoxication / Q000503:physiopathology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D004927:Escherichia coli Infections / Q000503:physiopathology*; D000431:Ethanol / Q000493:pharmacokinetics; D006820:Hyaluronic Acid / Q000493:pharmacokinetics*; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D008108:Liver Diseases, Alcoholic / Q000503:physiopathology*; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000503:physiopathology*
D001786:Blood Glucose; D000431:Ethanol; D006820:Hyaluronic Acid