Combination of N-(3׳,4׳-dimethoxycinnamoyl) anthranilic acid with cyclosporin A treatment preserves immunosuppressive effect and reduces the side effect of cyclosporin A in rat

Abstract

Cyclosporin A (CsA), one of the most fundamental immunosuppressive drugs, is routinely used in clinics for the treatment of liver and other organ rejections. However, one of the major challenges of the application of CsA is the occurrence of the serious adverse effects, namely, acute and chronic nephrotoxicity, severe hypertension and neurotoxicity. Although N-(3׳,4׳-dimethoxycinnamoyl) anthranilic acid (3,4-DAA) plays an important role in apoptosis of activated T cells, and is therapeutically used as an orally active anti-allergic drug for the treatment of allergy, it has not been tested for use in the treatment of organ rejection. In this study, we used the dark agouti (DA)-Lewis rat orthotopic liver transplantation (OLT) model to investigate whether the combination of 3,4-DAA with CsA is a promising and useful strategy to lower CsA dosage for reducing CsA side effect and preserve therapeutic effect of CsA. Here, we document that the combination treatment effectively inhibits acute liver rejection in OLT model with only half the normally suggested dosage of CsA that has much less side effect in rats than that of the full dosage. These results indicate that 3,4-DAA may serve as an effective adjunct for a CsA-based immunosuppressive regimen to treat transplant recipients for reducing CsA side effect.