Deferoxamine administration in septic animals: improved survival and altered apoptotic gene expression.
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).
Messaris
Evangelos
E
First Department of Propaedeutic Surgery, Hippocrateion Hospital, Athens Medical School, University of Athens, Vas Sofias 114, Ano Patisia, Athens 11141, Greece. messaris@compulink.gr
Antonakis
Pantelis T
PT
Memos
Nicholaos
N
Chatzigianni
Emmy
E
Leandros
Emanuel
E
Konstadoulakis
Manousos M
MM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053181:Caspase 8; D020169:Caspases / Q000096:biosynthesis; D045304:Cytochromes c / Q000096:biosynthesis; D003676:Deferoxamine / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D019254:Genes, bcl-2; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D016019:Survival Analysis; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C505528:Casp8 protein, rat; D053181:Caspase 8; D020169:Caspases; D003676:Deferoxamine