Hepatic preconditioning of doxorubicin in stop-flow chemotherapy：NF-kB／IkB-α pathway and expression of HSP72

AIM: To provide hepatic protection through administration of doxorubicin before stop-flow chemotherapy (SFC) and to investigate the expression of heat shock protein 72(HSP72) and role of nuclear factor kappa B (NF-kB) in this effect.METHODS: The hepatic preconditioning of doxorubicin was established in a porcine model by injection of doxorubidn(1 mg/kg) before SFC. The experimental animals were randomized into two groups: groups receiving doxorubicin(DOX) and normal saline (NS). Serial serum and tissue samples were taken from both groups to evaluate the protection of doxorubicin. Western blot and immunoprecipitation were applied to detect the expression of HSP72, NF-kB p65 protein, inhibitor kB-α (IkB-α) and phosphorylated IkB-α as well. The expression of tumor necrosis factor α (TNF-α) was estimated by semiquantitative RT-PCR. And the extent of the hepatic injury was estimated with the level of serum aminotransferases.RESULTS: An abundance production of HSP72 in porcine liver was observed after 24 h of intravenous administration of doxorubicin, but without any change in the expression of NF-kB p65 subunit in cytoplasm. NF-kB p65 subunit accumulated in nuclei at the end of SFC and reached its highest level at 30 rain after the restoration of the abdominal circulation and decreased gradually during the 6 h after SFC in NS group, while there was little change in DOX group. There was also a slight decrease of IkB-α at 30 min after the restoration of the abdominal circulation in NS group accompanying with the appearance of phosphorylated IkB-α. The expression of TNF-α was significantly higher in NS group than that in DOX group (average 1.40±0.17 vs 0.62±0.22, P