title: IGF-I/BP-3 administration preserves hepatic homeostasis after thermal injury which is associated with increases in no and hepatic NF-kappa B.
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 antiapoptotic 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 rhlGF-I/BP3 (10 mg/kg/day s.c.) 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-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) mRNA and hepatic nuclear-factor kappa B (NF-kappa B) 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-1 beta and TNF-alpha mRNA 1 day after burn (P < 0.05). IGF-I/BP-3 further increased hepatic NF-kappa B 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-kappa B.
authors.affiliation: Shriners Hospital for Children and Department of Surgery, University Texas Medical Branch, Galveston, Texas, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Jeschke
authors.forename: D N
authors.initials: DN
authors.lastname: Herndon
authors.forename: R
authors.initials: R
authors.lastname: Vita
authors.forename: D L
authors.initials: DL
authors.lastname: Traber
authors.forename: K W
authors.initials: KW
authors.lastname: Jauch
authors.forename: R E
authors.initials: RE
authors.lastname: Barrow
mesh_terms: D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases; D002056:Burns / Q000473:pathology / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects; D022781:Hepatocytes / Q000473:pathology; D006706:Homeostasis / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008099:Liver / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D014947:Wounds and Injuries / Q000378:metabolism*
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D016328:NF-kappa B; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D001219:Aspartate Aminotransferases