Liver preconditioning induced by iron in a rat model of ischemia/reperfusion

GALLEANO M; TAPIA G; PUNTARULO S; VARELA P; VIDELA LA; FERNANDEZ V

LIFE SCIENCES

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2011 vol. 80 p. 221 - 228

0024-3205

Liver preconditioning strategies are currently a major area of experimental and clinical research. In this study, iron administration (six doses of 50 mg iron-dextran/kg ip given every second day over a 10 days period) resulting in 22.9-fold, 8.3-fold, and 15.2-fold increases (P<0.05) in the hepatic content of total iron, labile iron, and ferritin, respectively, without significant changes in the serum levels of GOT and GPT assessed at day 13, induced 4.8-fold and 6.6-fold increases (P<0.05) in the hepatic protein carbonyl content and the protein carbonyl/glutathione (GSH) ratios at day 11 over control values, parameters that were normalized at day 13. Partial hepatic ischemia (1 h)-reperfusion (20 h) (IR) led to 6.1-fold and 12-fold enhancement (P<0.05) in the GOT and GPT levels in serum, respectively, and significant changes in liver histology, concomitantly with 110% increase in the serum levels of TNFalpha and 40% and 33% decreases in the hepatic NF-kappaB DNA binding (EMSA) and haptoglobin expression (Western blot), respectively. Iron administration exerted protection against hepatic IR injury, with 91% diminution in IR-induced TNF-alpha response and 75% recovery of NF-kappaB activation and haptoglobin expression that are lost during IR. In conclusion, iron administration underlying transient oxidative stress in the liver exerts hepatoprotection against IR injury that is related to abrogation of the inflammatory response and recovery of NF-kappaB activation and related acute-phase response signaling.