In vivo effects of lipopolysaccharide on hepatic free-NAD(P)(+)-linked redox states and cytosolic phosphorylation potential in 48-hour-fasted rats.
This study was performed to determine the magnitude and time of onset of in vivo changes in hepatic bioenergetics in response to a sublethal dose of lipopolysaccharide (LPS), a bacterial endotoxin. Male rats (48-hour-fasted) were administered an intraperitoneal injection of LPS (5 mg/kg body weight) or vehicle alone, and the livers were freeze-clamped 5, 30, or 180 minutes or 24 hours later. Liver tissue was extracted with perchloric acid, and the metabolites necessary to calculate NAD(+)- and NADP(+)-linked redox states and the cytosolic phosphorylation potential were measured. There was no significant difference in hepatic cytosolic phosphorylation potential between LPS and control groups at any of the times investigated. This indicated that the ability of the liver to synthesize adenosine triphosphate (ATP) was not compromised under the conditions of the study. No changes in hepatic redox states were observed 5 or 30 minutes after LPS treatment. Three hours after LPS treatment, hepatic cytosolic and mitochondrial free-[NAD+]/[NADH] redox states and the cytosolic free-[NADP+]/[NADPH] redox state were more oxidized. By 24 hours, only NAD(+)-linked redox states were more oxidized than the time-matched controls. Hepatic urea content was elevated at both 3 and 24 hours, compatible with an increased rate of urea synthesis as a consequence of increased amino acid metabolism, whereas hepatic beta-hydroxybutyrate and total ketone bodies were decreased 24 hours after LPS treatment, indicating decreased hepatic ketogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Gitomer
W L
WL
Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas 75235-9038, USA.
Miller
B C
BC
Cottam
G L
GL
D020155:3-Hydroxybutyric Acid; D000818:Animals; D003600:Cytosol / Q000378:metabolism*; D005215:Fasting; D006885:Hydroxybutyrates / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007657:Ketone Bodies / Q000378:metabolism; D007700:Kinetics; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D009243:NAD / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley; D014508:Urea / Q000378:metabolism
D006885:Hydroxybutyrates; D007657:Ketone Bodies; D008070:Lipopolysaccharides; D011773:Pyruvates; D009243:NAD; D009249:NADP; D019289:Pyruvic Acid; D014508:Urea; D020155:3-Hydroxybutyric Acid