title: Quantifying oxidative injury in the liver.
abstract: Oxidative injury is a mechanism common to both ischemia-reperfusion (IR) and leukocyte-mediated injury. Reperfused tissue beds and elaborated mediators can activate a cascade of intercellular and interorgan injuries that often precipitates multiple organ failure. Initiation of lung injury by gut IR is a case in point, but concomitant liver injury may have been overlooked because of the absence of comparably sensitive physiological markers. In this study, we explore the hypothesis that occurrence of portally derived oxidant-induced liver dysfunction may be detected with both sensitivity and specificity. We simulated pure oxidative injury to the liver and separated the contributions from secondary systemic oxidation. Both tissue and plasma indicators were evaluated, each reflecting aspects of oxidation, membrane integrity, and metabolic function. Tissue markers readily detect oxidative liver injury, but systemic 3-hydroxybutyrate (3-OHB) concentration and ketone body ratio (KBR) are the most sensitive. Comparison of 3-OHB concentrations against the corresponding KBR can be used to distinguish adjustments within a physiological range from the transition into injury.
authors.affiliation: Department of Surgery, Denver General Hospital, Colorado.
authors.forename: R S
authors.initials: RS
authors.lastname: Poggetti
authors.forename: E E
authors.initials: EE
authors.lastname: Moore
authors.forename: F A
authors.initials: FA
authors.lastname: Moore
authors.forename: K
authors.initials: K
authors.lastname: Koike
authors.forename: R
authors.initials: R
authors.lastname: Tuder
authors.forename: B O
authors.initials: BO
authors.lastname: Anderson
authors.forename: A
authors.initials: A
authors.lastname: Banerjee
mesh_terms: D020155:3-Hydroxybutyric Acid; D000818:Animals; D001646:Bile / Q000502:physiology; D056486:Chemical and Drug Induced Liver Injury; D005978:Glutathione / Q000378:metabolism; D006885:Hydroxybutyrates / Q000378:metabolism; D007657:Ketone Bodies / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D008297:Male; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010545:Peroxides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012711:Serum Albumin, Radio-Iodinated / Q000378:metabolism; D020122:tert-Butylhydroperoxide
chemical_list: D006885:Hydroxybutyrates; D007657:Ketone Bodies; D016877:Oxidants; D010545:Peroxides; D012711:Serum Albumin, Radio-Iodinated; D020122:tert-Butylhydroperoxide; D005978:Glutathione; D020155:3-Hydroxybutyric Acid