The effect of a bolus injection of TNF-alpha and IL-1 beta on hepatic energy metabolism in rats.
The effects of intravenous bolus injection of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) on hepatic mitochondrial energy metabolism were investigated in rats. The rats were injected with 15 micrograms/kg body wt of human recombinant TNF-alpha and IL-1 beta. The hepatic energy charge decreased to 0.794 +/- 0.005 and 0.789 +/- 0.006 in comparison with the sham control value of 0.838 +/- 0.007 and 0.835 +/- 0.011 at 12 and 24 hr after the treatment. The mitochondrial redox state (NAD+/NADH) increased from 17.4 +/- 1.9, 16.6 +/- 1.4, and 19.2 +/- 2.1 to 33.5 +/- 3.5, 27.8 +/- 2.8, and 30.9 +/- 2.6 concomitant with an increase in arterial blood ketone body ratio (acetoacetate/beta-hydroxybutyrate) from 0.49 +/- 0.04, 0.34 +/- 0.04, and 0.44 +/- 0.09 to 1.00 +/- 0.16, 0.69 +/- 0.13, and 0.86 +/- 0.15 at 3, 12, and 24 hr after the treatment. Total ketone body concentration in liver tissue and arterial blood was significantly lower at 24 hr after the treatment. State 3 respiration rate of isolated mitochondria increased by 29.2, 30.3, and 19.2% concomitant with an increase in oxidative phosphorylation rate by 26, 33.7, and 24.3% at 3, 12, and 24 hr after the treatment. These results showed that the administration of TNF-alpha and IL-1 beta in rats induced a hypermetabolic state in hepatic mitochondrial energy metabolism, which is a pattern similar to sepsis and presumably a compensatory reaction to the increased energy consumption.
Jin
M B
MB
Second Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Shimahara
Y
Y
Yamaguchi
T
T
Ichimiya
M
M
Kinoshita
K
K
Oka
T
T
Yamaoka
Y
Y
Ozawa
K
K
D000818:Animals; D004338:Drug Combinations; D004357:Drug Synergism; D004734:Energy Metabolism / Q000187:drug effects*; D007275:Injections, Intravenous; D007375:Interleukin-1 / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004338:Drug Combinations; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha