Oral administration of geranylgeranylacetone plus local somatothermal stimulation: a simple, effective, safe and operable preconditioning combination for conferring tolerance against ischemia-reperfusion injury in rat livers.
OBJECTIVE
To explore a simple, effective, safe and operable pretreatment for conferring tolerance against ischemia-reperfusion (I-R) injury in rat livers.


METHODS
Forty-five rats were divided into five groups (each group n = 9). Group C: control group; group G: geranylgeranylacetone (GGA) was administered without heat stress; group S: local heat stress alone; group WG: GGA plus whole-body heat stress; group SG: GGA administration plus local heat stress. After completion of the I-R procedure, the ischemic-reperfused liver lobes in five groups were resected and tested for heat shock protein (HSP70) by RT-PCR, Western blotting analysis and immunohistochemical staining. The blood samples were collected for ALT and AST measurement at the end of occlusion of blood supply, 30 min after reperfusion, 24, 48, 72 h after surgery from the inferior vena cava. Survival was monitored for 1 wk.


RESULTS
The production of HSP70 after I-R injury increased, the liver enzyme levels after reperfusion decreased rapidly, and the survival rates increased in groups C-SG.


CONCLUSIONS
The combination of GGA plus local somatothermal stimulation is a simple, effective, safe and operable pretreatment to induce HSP70 in patients with liver tumor and cirrhosis before hepatectomy and in donors before harvesting graft for liver transplantation.
Fan
Ning
N
Department of Laparoscopy, Affiliated Eastern Hospital of Hepatobiliary Surgery, Second Military Medical University, Shanghai 200438, China.
Yang
Guang-Shun
GS
Lu
Jun-Hua
JH
Yang
Ning
N
Zhang
Hai-Bin
HB
D000284:Administration, Oral; D000818:Animals; D004224:Diterpenes / Q000008:administration & dosage* / Q000494:pharmacology*; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response; D006979:Hyperthermia, Induced; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; C031049:geranylgeranylacetone