EFFECT OF CYCLOSPORINE WITHDRAWAL AFTER SHORT- AND LONG·TERM CYCLOSPORINE A EXPOSURE ON THE KIDNEY OF MALE ALBINO RATS

The cyclic fungal peptide, Cyclosporine A (CsA) is one of the most potent immunosuppressants used for the management of multiple-orqan transplantation. CsA has improved early (1year) graft survival rates after kidney, heart, liver, pancreas and bone marrow transplantation and has contributed to ameliorate the treatment of autoimmune diseases refractory
to conventional therapy (Goral et aI., 1997; Kagawa et aI., 2003; Ziolkowski et aI., 2003; Hesselink et aI., 2004) . The immunosuppressive effect of GsA is achieved through its impairment to interleukin-2 (IL-2) production
resulting in inhibition of calcineurin that is involved in activation of T lymphocytes. Consequently, calcineurin inhibition blocks immune cell mediated reaction against the transplanted tissue (Faulds et al.,1993). However,
the introduction of this drug did not translate into improved long-term graft survival. There is considerable concern that one reason for this is that on the long-term, CsA nephrotoxic effects counteract the protective role of
the drug as immunosuppressant (Cattaneo et al., 2004).