The effect of combination therapy with EPC-K1 and low-dose cyclosporine to pulmonary allograft after rat lung transplantation
| Autor: | T, Udaka, T, Misao, M, Aoe, H, Date, A, Andou, N, Shimizu |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Graft Rejection
Male Dose-Response Relationship Drug Ascorbic Acid Free Radical Scavengers Antioxidants Phospholipases A Rats Phospholipases A2 Rats Inbred Lew Rats Inbred BN Cyclosporine Animals Vitamin E Drug Therapy Combination Lymphocyte Culture Test Mixed Lung Immunosuppressive Agents Lung Transplantation |
| Zdroj: | The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 16(8) |
| ISSN: | 1053-2498 |
| Popis: | EPC-K1, a diester of alpha-tocopherol and ascorbic acid, has a hydroxyl radical scavenging effect and also has antiinflammatory properties through its phospholipase A2 inhibitory effect. With a view to decreasing the total dose of cyclosporine, the effect of a combination of EPC-K1 and cyclosporine on rejection was investigated by use of a rat orthotopic left lung transplantation model.Orthotopic left lung transplantation was performed with brown Norway rats as donors and Lewis rats as recipients. Recipients were assigned to one of four experimental groups. Control group animals were given no immunosuppression. The EPC-K1 group received continuous intraperitoneal infusion of EPC-K1 (5 mg/kg/day) by osmotic pump on postoperative days (POD) 0 through 6. The cyclosporine group received cyclosporine (1.25 mg/kg/day) intramuscularly on POD 1 through 6. The EPC-K1 + cyclosporine group received both EPC-K1 and cyclosporine in the same manner as the EPC-K1 and cyclosporine groups. Recipients were killed on POD 7, and the transplanted lungs were examined histologically and graded in a blinded fashion (grade 0 to 4). The effect of EPC-K1 and cyclosporine treatment on the primary immune response was examined by mixed lymphocyte reaction (MLR) between brown Norway rat stimulator cells (treated with mitomycin) added to Lewis rat responder lymphocytes.Control group animals exhibited the severe destructive changes of grade 4 lung rejection. The EPC-K1 + cyclosporine group showed significantly less graft rejection compared with the EPC-K1 group and the cyclosporine group (p0.01). In MLR assay, the EPC-K1 + cyclosporine group (793 +/- 210 cpm) showed significantly suppressed lymphocyte proliferation compared with the control group (2188 +/- 360 cpm), EPC-K1 group (1869 +/- 541 cpm), and cyclosporine group (1873 +/- 326 cpm) (p0.01).EPC-K1 significantly improves effects of cyclosporine at lower doses both in preventing pulmonary allograft rejection and in suppressing lymphocyte proliferation in MLR. |
| Databáze: | OpenAIRE |
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