Evaluation of the Role of Mitochondria in Drug-Induced Toxicity
Project no. 257 · Status: Kapanmış · 2016
Summary
Mitochondria are organelles where the cellular energy is produced and oxidative respiration as well as many other vital physiological processes take place. Therefore, any structural or functional disorders in mitochondria may cause drastic reasults in the organism. In this project, it has been aimed to investigate the effects of various drugs on mitochondria whose toxic mechanisms are unclear. The effects of clozapine, nifedipine, diclofenac and valproic acid on mitochondrial ATP production and mitochondrial membranes in the presence or absence of calcium, were investigated. ATP measurement was performed by two different methods and it was shown that HPLC is superior method than bioluminescence. It was found that clozapine and diclofenac inhibits ATP production and diclofenac and valproic acid have been found to increase the formation of calcium-induced MPTP, but none of the drugs was found to induce MPTP formation alone. Developed experimental approaches may be used for reveal the toxicity mechanisms of these drugs and screening the mitochondrial toxicity of other drugs, drug candidates or chemicals. Key words: mitochondria; ATP production; MPTP; clozapine; nifedipine; diclofenac; valproik acid