IGF-I/BP-3 administration preserves hepatic homeostasis after thermal injury which is associated with increases in NO and hepatic NF-κB

Marc G. Jeschke, David Herndon, Randi Vita, Daniel L. Traber, Karl Walter Jauch, Robert E. Barrow

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

After a severe trauma, such as a cutaneous thermal injury, an increase in hepatocyte apoptosis has been associated with hepatocyte damage and impairment in hepatic function, Insulinlike growth factor-I (IGF-I) exerts anti-apoptotic effects in several organs, thus improving organ homeostasis. The purpose of the present study was to determine whether IGF-I in combination with its principle binding protein-3 (BP-3) attenuates liver damage after a burn and whether this attenuation is through signals of the apoptotic-proliferative axis of hepatocytes. Sprague-Dawley rats (56 males) received a 60% total body surface area third-degree scald burn and were randomly divided to receive either rhIGF-I/BP3 (10 mg/kg/day sc.) or saline (control). Serum aspartate transaminase (AST) and nitric oxide (NO), and hepatocyte proliferation and apoptosis, were measured on postburn days 1, 2, 5, and 7. Hepatic interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) mRNA and hepatic nuclear-factor κB (NF-κB) were determined at 1 and 2 days postburn. IGF-I/BP-3 decreased serum AST and increased serum NO at 1, 2, and 5 days after burn when compared with controls (P < 0.05). IGF-I/BP-3 increased hepatocyte proliferation on the first day after burn and decreased hepatocyte apoptosis at day 7 postburn when compared with controls (P < 0.05). IGF-I/BP-3 decreased hepatic IL-1β and TNF-α mRNA 1 day after burn (P < 0.05). IGF-I/BP-3 further increased hepatic NF-κB concentration 1 and 2 days postburn when compared with controls (P < 0.05). Recombinant hIGF-I in combination with its principle binding protein conserves hepatic homeostasis, which is associated with a transient increase in hepatocyte proliferation and decrease in hepatocyte apoptosis possibly through NO and hepatic NF-κB.

Original languageEnglish (US)
Pages (from-to)373-379
Number of pages7
JournalShock
Volume16
Issue number5
StatePublished - Nov 2001

Fingerprint

Hepatocytes
Intercellular Signaling Peptides and Proteins
Carrier Proteins
Nitric Oxide
Homeostasis
Hot Temperature
Liver
Wounds and Injuries
Apoptosis
Aspartate Aminotransferases
Interleukin-1
Tumor Necrosis Factor-alpha
Serum
Messenger RNA
Body Surface Area
Sprague Dawley Rats
Skin

Keywords

  • Apoptosis
  • IGF-I
  • IGFBP-3
  • Liver
  • NF-κB
  • Proliferation
  • Thermal injury

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine

Cite this

Jeschke, M. G., Herndon, D., Vita, R., Traber, D. L., Jauch, K. W., & Barrow, R. E. (2001). IGF-I/BP-3 administration preserves hepatic homeostasis after thermal injury which is associated with increases in NO and hepatic NF-κB. Shock, 16(5), 373-379.

IGF-I/BP-3 administration preserves hepatic homeostasis after thermal injury which is associated with increases in NO and hepatic NF-κB. / Jeschke, Marc G.; Herndon, David; Vita, Randi; Traber, Daniel L.; Jauch, Karl Walter; Barrow, Robert E.

In: Shock, Vol. 16, No. 5, 11.2001, p. 373-379.

Research output: Contribution to journalArticle

Jeschke, MG, Herndon, D, Vita, R, Traber, DL, Jauch, KW & Barrow, RE 2001, 'IGF-I/BP-3 administration preserves hepatic homeostasis after thermal injury which is associated with increases in NO and hepatic NF-κB', Shock, vol. 16, no. 5, pp. 373-379.
Jeschke, Marc G. ; Herndon, David ; Vita, Randi ; Traber, Daniel L. ; Jauch, Karl Walter ; Barrow, Robert E. / IGF-I/BP-3 administration preserves hepatic homeostasis after thermal injury which is associated with increases in NO and hepatic NF-κB. In: Shock. 2001 ; Vol. 16, No. 5. pp. 373-379.
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