Cyclosporine A: Chemistry and Toxicity – A Review

Abstract

: Cyclosporine A (CsA) is a cyclic undecapeptide with strong immunosuppressive potency. Firstly marketed in the mid-1980s, CsA was widely used in transplantation and greatly improved the survival rates of patients and grafts after solidorgan transplantation. Unfortunately, CsA administration can be associated with a number of side effects due to its high toxicity. These side effects seriously limited the clinical use of CsA. Therefore, it is important to understand the serious side effects of CsA in patients, especially in transplantation. In this review article, we are summarizing the chemistry and most known toxic effects of CsA including the nephrotoxic, hepatotoxic, neurotoxic and cardiotoxic effects. Its available toxicity data (different species, different administration routes) published formerly are also summarized. In addition, the molecular pathways of toxic damage induced by CsA are also detailly discussed. We hope that this review will help to further understand the source, chemistry and clinical application of CsA in patients as well as the potential mechanisms of CsA-induced toxicity.