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 which protects liver against ischaemia-reperfusion injury (IRI). The aim of this study was to determine, in an animal model, whether intravenous administration of doxorubicin induces heat shock proteins (HSPs) in liver tissue and facilitates liver tolerance to subsequent warm IRI.


METHODS
Male Wistar rats were used. Production of HSPs was determined in liver tissue sequentially after the injection of doxorubicin 1 mg/kg body-weight. Acquisition of tolerance for 30 min warm ischaemia and reperfusion of the liver was determined in animals pretreated (48 h beforehand) with doxorubicin, and in controls. Biochemical liver function and liver adenine nucleotide concentration 40 min after reperfusion and survival rate at 7 days after the ischaemic insult were recorded.


RESULTS
Expression of HSP72 and HSP73 in the liver was confirmed 48 h after doxorubicin administration. Biochemical parameters and survival rates were significantly better in pretreated animals than in controls.


CONCLUSIONS
These results indicate that doxorubicin has the potential to provide the liver with tolerance against IRI. A simultaneous increase of both HSP72 and HSP73 in liver tissue may explain the acquisition of tolerance following the administration of doxorubicin.
Kume
M
M
Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo, Kyoto 606-8507, Japan.
Yamamoto
Y
Y
Yamagami
K
K
Ishikawa
Y
Y
Uchinami
H
H
Yamaoka
Y
Y
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D004317:Doxorubicin / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007511:Ischemia / Q000517:prevention & control; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D013312:Stress, Physiological / Q000139:chemically induced* / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin