Immunosuppression by combined use of cyclosporine and resveratrol in a rat liver transplantation model.
Transplant Proc. 2005 Jun;37(5):2354-9. PMID: 15964415
INTRODUCTION: Despite continued progress in the development of immunosuppressive agents, allograft rejection remains an important cause of morbidity and mortality after liver transplantation. We examined the effect of intraperitoneal injection of cyclosporine (CsA) and resveratrol (Res) on allograft rejection after liver transplantation in rats. METHODS: Male Sprague-Dawley rats were selected as donors and male Wistar rats as recipients for a rejection model. The recipients were divided into three groups after orthotopic liver transplantation (OLTx): in the combination group both Res (100 mg/kg) and CsA (20 mg/kg) were given by intraperitoneal route once a day, whereas in the CsA group or control group CsA (20 mg/kg) or vehicle buffer was given. The survival period, serum chemistry, production of some cytokines, activation of transcription factor NF- kappaB, and histopathological findings were then compared among them. RESULTS: The mean survival period after OLTx in the combination group was significantly longer than that in the CsA group or control group (P < .05 and P < .01). On posttransplant day 7, the serum albumin level significantly improved, the serum total bile acid and alanine aminotransferase levels were significantly lower, the serum interleukin-2 and interferon-gamma levels were significantly lower, and the activation of transcription factor NF-kappaB in peripheral blood T lymphocytes was significantly suppressed in the combination group in comparison with those in the CsA group (all P < .05) or control group (all P < .01), and a histological examination revealed apparent difference in the severity of rejection between the combination group and CsA group (P < .05) or control group (P < .01). CONCLUSION: The combined use of CsA and Res has a stronger immunosuppressive effect on hepatocytes under allograft rejection in comparison with the sole use of CsA. Res might serve as a novel supplementary immunosuppressive agent for reducing the severity of hepatic allograft rejection in rats.