The immunosuppressive effect of 5-lipoxygenase inhibitor on liver allotransplantation in rats.
This study was performed to examine the immunosuppressive effect of a 5-lipoxygenase inhibitor, AA-861, on liver transplantation in rodents, and also to examine the production of eicosanoids during rejection of liver allograft in these animals. Rats were divided into three groups: group I (syngenic orthotopic liver transplantation from LEW to LEW), group II (allogenic OLT from ACI to LEW with dimethyl sulfoxide), and group III (allogenic OLT from ACI to LEW with AA-861 [20 mg/kg/day] s.c. dissolved in DMSO). Histological examinations were performed, survival time was monitored, and eicosanoid levels at 3, 5, and 7 days after transplantation were measured. Mean survival time in group III was significantly longer than that in group II (36.0 +/- 6.8 vs. 11.1 +/- 0.7 days, mean +/- SEM; P < 0.01). Histologically, the degree of rejection in group III was moderate compared with that in group II. On day 3, the LTB4 level in group II was significantly higher than that in group I (3361 +/- 985 vs. 407 +/- 70 pg/ml, P < 0.05), and the PGE2 level in group III was significantly higher than that in group 1 (50.3 +/- 4.8 vs. 23.5 +/- 4.7 pg/ml, P < 0.01) and in group II (32.9 +/- 4.2 pg/ml, P < 0.05). These findings suggest that AA-861 reduced liver allograft rejection by suppressing the elevation of 5-lipoxygenase products and increasing PGE2 production in the early stage of rejection.
Iyobe
T
T
Department of Surgery II, School of Medicine, University of Kanazawa, Japan.
Izumi
R
R
Shimizu
K
K
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D015777:Eicosanoids / Q000097:blood; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D016031:Liver Transplantation / Q000276:immunology* / Q000401:mortality; D008297:Male; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D015996:Survival Rate; D014184:Transplantation, Homologous / Q000276:immunology
D016227:Benzoquinones; D015777:Eicosanoids; D007166:Immunosuppressive Agents; D016859:Lipoxygenase Inhibitors; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D000410:Alanine Transaminase