Exploring cyclosporine A-side effects and the protective role-played by antioxidants: the morphological and immunohistochemical studies
R. Rezzani
Division of Human Anatomy, Department of Biomedical Sciences and Biotechnologies, University of Brescia, Brescia, Italy.
Offprint requests to: Dr. Rita Rezzani, Division of Human Anatomy, Department of Biomedical Sciences and Biotechnologies, University of Brescia, Viale Europa 11, 25123 Brescia, Italy. e-mail: rezzani@med.unibs.it
Summary. Cyclosporine A (CsA) is the immunosuppressor most frequently used in transplant surgery and in the treatment of autoimmune diseases, because of its specific inhibiting effect on the signal transduction pathways of cell T receptor. It has been shown that CsA is able to generate reactive oxygen species and lipid peroxidation, which are directly involved in the CsA nephrotoxicity, hepatotoxicity and cardiotoxicity. So, the use of antioxidants seems to be a useful tool in attempting to reduce CsA adverse effects. The aim of this review is to summarise the general aspect of CsA, the classification of antioxidants, their mechanism of action and their administration for improving CsA side effects.
The protective role of different antioxidants has been evaluated on CsA-induced nephrotoxicity. It has been shown that the antioxidants, improved the morphological renal cytoarchitecture, increased the antioxidant enzyme content, decreased lipid peroxidation and reactive species oxygen (ROS).
The protective role of antioxidants was also found in CsA hepatotoxicity and was related to the increase in antioxidant capacity of hepatic tissue, which was responsible for ameliorating hepatic morphology.
Recently, it has been demonstrated that CsA induces side effects on the heart but the data to this purpose are very few and also the number of results on the protective role played by antioxidants it is very limited.
In conclusion, not only do these observations provide insight into the intricate mechanism of CsA adverse effects, but they also present novel opportunities for the design and development of more effective therapeutic strategies against negative effects. Histol Histopathol 21, 301-316 (2006)
Key words: Cyclosporine A, Antioxidants, Kidney, Liver, Heart
DOI: 10.14670/HH-21.301