Ultrastructural examination of renal tubular epithelial cells and hepatocytes in the course of chronic cyclosporin A treatment--a possible link to oxidative stress.

Cyclosporin A is an immunosuppressant drug used to prevent graft rejection in organ transplantation. Side effects include toxicity to the kidney and liver. Recently, many experimental and clinical data have demonstrated that CsA-induced toxicity is associated with increased production of reactive oxygen species (ROS) and lipid peroxidation in the kidney and liver. The aim of the study was ultrastructural examination of renal and liver epithelial cells in the course of chronic experimental CsA treatment. Rats were treated with CsA in a dose of 25 mg/kg/day. Animals developed failure of the kidney and the liver functions manifested by an increase in serum levels of creatinine, urea, uric acid, bilirubin, AST, and ALT and a decrease in total proteins. Ultrastructural examination of tubular epithelial cells and hepatocytes revealed dilatation of endoplasmic reticulum and injury to mitochondria, formation of autolysosomes, and presence of single apoptotic cells. On the basis of a review of the literature the authors suggest that mitochondrial and cell membrane system changes are, at least in part, a result of oxidative damage to the liver and renal tubular epithelial cells.