Pharmacological hepatic preconditioning: involvement of 70-kDa heat shock proteins (HSP72 and HSP73) in ischaemic tolerance after intravenous administration of doxorubicin

Background: Pharmacological preconditioning may induce a stress response wh ich protects liver against ischaemia-reperfusion injury (IRI). The aim of t his study was to determine, in an animal model, whether intravenous adminis tration of doxorubicin induces heat shock proteins (HSPs) in liver tissue a nd facilitates liver tolerance to subsequent warm IRI. Methods: Male Wistar rats were used. Production of HSPs was determined in l iver tissue sequentially after the injection of doxorubicin 1 mg/kg body-we ight. Acquisition of tolerance for 30 min warm ischaemia and reperfusion of the liver was determined in animals pretreated (48 h beforehand) with doxo rubicin, and in controls. Biochemical liver function and liver adenine nucl eotide concentration 40 min after reperfusion and survival rate at 7 days a fter the ischaemic insult were recorded. Results: Expression of HSP72 and HSP73 in the liver was confirmed 48 h afte r doxorubicin administration. Biochemical parameters and survival rates wer e significantly better in pretreated animals than in controls. Conclusion: These results indicate that doxorubicin has the potential to pr ovide the liver with tolerance against IRI. A simultaneous increase of both HSP72 and HSP73 in liver tissue may explain the acquisition of tolerance f ollowing the administration of doxorubicin.