Adaptational increase of liver glutathione content during long-term application of cyclosporine A may attenuate toxic side effects.

The concentrations of reduced and oxidized glutathione and of adenine nucleotides were deterrmined in liver, kidney and heart of rats during long-term (four weeks), high-dose therapy with cyclosporine A. In liver and kidney the concentration of oxidized glutathione increased following 4 weeks-therapy suggesting increased formation of free radicals and accelerated lipid peroxidation processes. These processes may be due to an increased activity of the cytochrome P-450 system. Compensatory levels of reduced glutathione were also increased. The adaptational increase of the tissue level of reduced glutathione, presumably the response to a chronic oxidative stres, was more distinct in the liver