The Effect of a Bolus Injection of TNF-α and IL-1β on Hepatic Energy Metabolism in Rats

• Published in: The Journal of surgical research 1995-05, Vol.58 (5), p.509-515
• Main Authors: Jin, Maeng Bong, Shimahara, Yasuyuki, Yamaguchi, Tetsuya, Ichimiya, Masato, Kinoshita, Kouichi, Oka, Takahiro, Yamaoka, Yoshio, Ozawa, Kazue
• Format: Article
• Language: English
• Subjects: Animals; Bacterial diseases; Bacterial sepsis; Biological and medical sciences; Drug Combinations; Drug Synergism; Energy Metabolism - drug effects; Human bacterial diseases; Infectious diseases; Injections, Intravenous; Interleukin-1 - pharmacology; Liver - drug effects; Liver - metabolism; Male; Medical sciences; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Rats; Rats, Wistar; Recombinant Proteins; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.1995.1080

The effects of intravenous bolus injection of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) on hepatic mitochondrial energy metabolism were investigated in rats. The rats were injected with 15 μg/kg body wt of human recombinant TNF-α and IL-1β. 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/β-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-α and IL-1β 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.