Prevention of postischaemic lipid peroxidation and liver cell injury by iron chelation.

Abstract

Liver ischaemia was induced by cross clamping the hilar pedicle for 30 minutes in groups of rats with or without treatment with the iron chelating agent desferrioxamine (deferoxamine, DFR). The groups included eight animals each and were divided into the following treatment categories: control; ischaemia alone; ischaemia with subsequent reperfusion; ischaemia preceded by DFR, 60 mg/kg body weight; and reperfusion preceded by 20, 40, or 60 mg/kg DFR. The drug was given intravenously five minutes before either ischaemia or reperfusion. Malondialdehyde (MDA), a product of lipid peroxidation, and histopathological changes of liver tissue samples were used as indicators of hepatocellular injury. Lipid peroxidation (MDA concentration in mumol/kg liver tissue) was highest (4.76 (1.19] after ischaemia without reperfusion and less pronounced (2.87 (0.34] after reperfusion. Both concentrations, however, were significantly (p less than 0.05) higher than basal (control) values (1.78 (0.27]. At 60 mg/kg body weight, DFR treatment reduced MDA to basal or even lower concentrations in both situations (1.98 (0.08) and 1.26 (0.06), respectively) with a corresponding improvement in liver histopathology. Lower DFR doses were less protective. The data suggest that liver ischaemia is associated with free radical initiated, and apparently iron catalysed lipid peroxidation, which can be significantly decreased by iron chelation.