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

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.