[The influence of tacrolimus on oxidative stress and free-radical processes]

Oxidative stress causes disturbances in homeostasis leading to an excessive production of reactive oxygen species (ROS). Free-radical reactions undergo intensification during transplantation and are responsible for both damage to the graft and cardiovascular complications, one of the major causes of patient death. The function of immunosuppressive drugs in this process is currently the object of research. Investigations of medications which would decrease the level of oxidative stress are in progress. Tacrolimus (FK-506) is a medication commonly used in immunosuppressive therapy. It has a better cardiac-lipid profile than cyclosporine A. Some reports about the beneficial effect of tacrolimus on the level of oxidative stress in the organism have appeared. Especially in vitro studies and animal tests indicate antioxidative properties for tacrolimus. Decreases in parameters of oxidative stress, such as the concentration of malone dialdehyde (MDA), the activity of myeloperoxidase (MPO), and neutrophilic infiltration, were observed after treatment. In in vitro studies on endotheliocytes, tacrolimus induced oxidative stress more weakly than other medications and was the only one that did not increase the production of nitric oxide (NO). The protective effect of tacrolimus on inflammatory response in rat liver during ischemia-reperfusion injury, on atrocytes exposed to stimulated ischemia in vitro, and in experimental traumatic injury of spinal cord tissues in rats were also described. Findings in patients after transplantation are not so clear and even indicate that the influence of tacrolimus on the activity of antioxidative enzymes in kidneys may be involved in side-effect of tacrolimus.