Wl. Gitomer et al., IN-VIVO EFFECTS OF LIPOPOLYSACCHARIDE ON HEPATIC FREE-NAD(P)(-LINKED REDOX STATES AND CYTOSOLIC PHOSPHORYLATION POTENTIAL IN 48-HOUR-FASTEDRATS()), Metabolism, clinical and experimental, 44(9), 1995, pp. 1170-1174
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 (4
8-hour-fasted) were administered an intraperitoneal injection of LPS (
5 mg/kg body weight) or vehicle alone, and the livers were freeze-clam
ped 5, 30, or 180 minutes or 24 hours later. Liver tissue was extracte
d 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 hepat
ic cytosolic phosphorylation potential between LPS and control groups
at any of the times investigated. This indicated that the ability of t
he liver to synthesize adenosine triphosphate (ATP) was not compromise
d under the conditions of the study. No changes in hepatic redox state
s were observed 5 or 30 minutes after LPS treatment. Three hours after
LPS treatment, hepatic cytosolic and mitochondrial free-[NAD(+)]/[NAD
H] redox states and the cytosolic free-[NADP(+)]/[NADPH] redox state w
ere more oxidized. By 24 hours, only NAD(+)-linked redox states were m
ore 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, wh
ereas hepatic beta-hydroxybutyrate and total ketone bodies were decrea
sed 24 hours after LPS treatment, indicating decreased hepatic ketogen
esis. The oxidation of hepatic NAD(+) redox states in response to LPS
appears to be due to a change in the metabolic fuels available to the
liver; however, a partial uncoupling of oxidative phosphorylation cann
ot be ruled out. Copyright (C) 1995 by W.B. Saunders Company