Protection against acetaminophen-induced liver injury in vivo by an iron chelator, deferoxamine.
BACKGROUND
Recent data indicate that iron ions play a major role in lipid peroxidation, a hepatotoxic effect of acetaminophen (APAP).


METHODS
We investigated whether an iron chelator, deferoxamine (DFO), can protect against APAP-induced liver injury in vivo in rats.


RESULTS
DFO diminished the increase in serum alanine aminotransferase (ALAT) in a dose-dependent manner after APAP administration and also reduced mortality. Administration of 750 mg/kg APAP resulted in an increased ALAT (11,666 +/- 4633) after 8 h, and the mortality at 24 h was 88%. Pretreatment with 200 mg/kg DFO for 1 h significantly reduced ALAT (to 3406 +/- 894) and mortality (38%). DFO also attenuated histopathologic changes. Treatment with DFO depressed malondialdehyde formation by APAP without inhibiting glutathione depletion in the liver or reducing covalent binding of [3H]APAP to liver proteins.


CONCLUSIONS
These results indicate that the protective effect of DFO against APAP-induced liver injury may be attributable not to changes in APAP metabolism but to the chelation of iron, which can catalyze the generation of active oxygen species, in hepatocytes.
Sakaida
I
I
First Dept. of Internal Medicine, Yamaguchi University, School of Medicine, Ube, Japan.
Kayano
K
K
Wasaki
S
S
Nagatomi
A
A
Matsumura
Y
Y
Okita
K
K
D000082:Acetaminophen / Q000009:adverse effects*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D003676:Deferoxamine / Q000627:therapeutic use*; D005978:Glutathione / Q000032:analysis; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D008099:Liver / Q000737:chemistry; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D007502:Iron Chelating Agents; D000082:Acetaminophen; D000410:Alanine Transaminase; D005978:Glutathione; D003676:Deferoxamine