Efficiency of pentoxifylline in donor pretreatment in rat liver transplantation.
Donor pretreatment is a new concept in organ preservation. Pentoxifylline (PTX) has been reported to suppress the activation of Kupffer cells and to decrease injury to the hepatic graft after rat liver transplantation. We evaluated the efficiency of PTX pretreatment on the donor against hepatic injury following cold ischemia (CI) or warm ischemia (WI) using the rat liver transplantation model. Dose dependency: every rat was injected intraperitoneally with PTX (30, 50, or 80 mg/kg) or saline. One hour later, the portal vein (PV) and the hepatic artery (HA) were clamped for 30 min. Transplantation: the donor rat was injected intraperitoneally with 50 mg/kg PTX or saline, 1 hr before laparotomy. Animals were divided into two groups. In the CI group, grafts were preserved for 12 hr in University of Wisconsin solution at 4 degrees C and transplanted. In the WI group, the PV and the HA in the donor were clamped for 30 min before donor surgery, and the grafts were transplanted. Serum levels of tumor necrosis factor-alpha (TNF-alpha), glutathione S-transferase-alpha (GST-alpha), and aspartate transaminase (AST) were measured at 30 min, 3 hr, and 24 hr after reperfusion of the PV. Compared with those of a control group, the serum levels of TNF-alpha, GST-alpha, and AST in the PTX-pretreated groups were significantly lower after both CI and WI at 30 min and further suppressed in the WI group at 24 hr. These results indicate that PTX pretreatment on the donor is effective for suppression of hepatic injury after both CI and WI.
Nishizawa
H
H
Department of Transplantation Immunology, Kyoto University Graduate School of Medicine, Kyoto, 606-01, Japan.
Egawa
H
H
Inomata
Y
Y
Uemoto
S
S
Asonuma
K
K
Kiuchi
T
T
Yamaoka
Y
Y
Tanaka
K
K
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005982:Glutathione Transferase / Q000097:blood; D007274:Injections, Intraperitoneal; D007770:L-Lactate Dehydrogenase / Q000097:blood; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D010431:Pentoxifylline / Q000008:administration & dosage / Q000494:pharmacology*; D011300:Preoperative Care; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013696:Temperature; D013997:Time Factors; D014019:Tissue Donors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D007770:L-Lactate Dehydrogenase; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D010431:Pentoxifylline