Presented to the annual meetings of the American Gastroenterological Association and the American Association for the Study of Liver Disease (Digestive Disease Week 1997), 11–14 May 1997, Washington, DC, USA; the 32nd Congress of the European Society for Surgical Research, 18–21 May 1997, Corfu, Greece; the Fourth Congress of the Asian Society of Hepato-Biliary-Pancreatic Surgery, 19–21 June 1997, Tokyo, Japan; and the 37th World Congress of the International Society of Surgery, International Surgical Week, 24–30 August 1997, Acapulco, Mexico
Pharmacological hepatic preconditioning: involvement of 70-kDa heat shock proteins (HSP72 and HSP73) in ischaemic tolerance after intravenous administration of doxorubicin†
Article first published online: 6 DEC 2002
© 2000 British Journal of Surgery Society Ltd
British Journal of Surgery
Volume 87, Issue 9, pages 1168–1175, 1 September 2000
How to Cite
Kume, M., Yamamoto, Y., Yamagami, K., Ishikawa, Y., Uchinami, H. and Yamaoka, Y. (2000), Pharmacological hepatic preconditioning: involvement of 70-kDa heat shock proteins (HSP72 and HSP73) in ischaemic tolerance after intravenous administration of doxorubicin. Br J Surg, 87: 1168–1175. doi: 10.1046/j.1365-2168.2000.01509.x
- Issue published online: 6 DEC 2002
- Article first published online: 6 DEC 2002
- Manuscript Accepted: 8 MAR 2000
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.
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.
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.
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. © 2000 British Journal of Surgery Society Ltd