BACKGROUND: Oxidative damage is one of the major factors that lead to cell damage, organ dysfunction and death in sepsis. Thus, an attractive candidate for the pharmacologic treatment of the septic syndrome is desferoxamine (DFX), an antioxidant iron chelator used for the removal of iron and a potential free radical scavenger. OBJECTIVE: The impact of DFX administration on the survival of septic animals. The effect on cell integrity and cycle of vital organs. METHODS: Sepsis was induced in 40 rats using the cecal ligation and puncture method (CLP) and 20 rats randomly received twice subcutaneously DFX (total dose: 40 mg/kg). Rats were monitored for 36 h and all vital organs were harvested for pathology examination and immunohistochemical detection of Bax, Bcl-2, cytochrome c and caspase-8 apoptosis regulating proteins. RESULTS: Mean survival in the DFX group was 34.2 h (median 36.0, S.D. 4.4) and 30.2 h (median 36.0, S.D. 9.1) in the control group (p=0.04), while 36 h after follow up 85% of the DFX-treated rats and 55% of placebo rats were alive (p=0.04). Expression of pro-apoptotic bax protein was significantly increased in the heart, liver and kidney of animals in the DFX group compared to the control group. CONCLUSIONS: Treatment with the polymeric iron chelator DFX significantly increases survival of septic subjects and alters the expression of bax, an apoptosis regulating protein in certain organs (heart, liver and kidney).
BACKGROUND: Oxidative damage is one of the major factors that lead to cell damage, organ dysfunction and death in sepsis. Thus, an attractive candidate for the pharmacologic treatment of the septic syndrome is desferoxamine (DFX), an antioxidant iron chelator used for the removal of iron and a potential free radical scavenger. OBJECTIVE: The impact of DFX administration on the survival of septic animals. The effect on cell integrity and cycle of vital organs. METHODS:Sepsis was induced in 40 rats using the cecal ligation and puncture method (CLP) and 20 rats randomly received twice subcutaneously DFX (total dose: 40 mg/kg). Rats were monitored for 36 h and all vital organs were harvested for pathology examination and immunohistochemical detection of Bax, Bcl-2, cytochrome c and caspase-8 apoptosis regulating proteins. RESULTS: Mean survival in the DFX group was 34.2 h (median 36.0, S.D. 4.4) and 30.2 h (median 36.0, S.D. 9.1) in the control group (p=0.04), while 36 h after follow up 85% of the DFX-treated rats and 55% of placebo rats were alive (p=0.04). Expression of pro-apoptotic bax protein was significantly increased in the heart, liver and kidney of animals in the DFX group compared to the control group. CONCLUSIONS: Treatment with the polymeric iron chelator DFX significantly increases survival of septic subjects and alters the expression of bax, an apoptosis regulating protein in certain organs (heart, liver and kidney).
Authors: Lucas T van Eijk; Suzanne Heemskerk; Rob W van der Pluijm; Susanne M van Wijk; Wilbert H M Peters; Johannes G van der Hoeven; Matthijs Kox; Dorine W Swinkels; Peter Pickkers Journal: Haematologica Date: 2013-11-15 Impact factor: 9.941