Need for Effective Parameters

Critical for predictivity in a recent comprehensive study was the number and choice of parameters measured [4]. Early, sublethal effects on cell proliferation, cell morphology and mitochondria occurred consistently and ubiquitously with toxicity and when used collectively were most diagnostic. It is noteworthy that the toxicity of many drugs is attributable to various mitochondrial targets, including oxidative phosphorylation, fatty acid oxidation, Krebs cycling, membrane transport, permeability transition pore, proliferation and oxidative stress (Table 14.4). [Pg.334]

Fatty acid beta-oxidation Inhibition by valproate, tetracyclines, nonsteroidal antiinflammatory drugs, antianginal cationic amphiphilic drugs, female sex hormones, CoA depleters such as valproate and salicylate [Pg.334]

Krebs cycle Inhibition of aconitase by superoxide and fluoroacetate, of succinate dehydrogenase by methamphetamine and mal-onate, of alpha-ketoglutarate dehydrogenase by salicylic add [Pg.334]

Membrane transporters Inhibition of adenine nudeotide transporter by zidovudine [Pg.334]

Permeability transition pore Opening by reactive oxygen species, reactive nitrogen species, bile adds, ihio crosslinkers, atractyloside, betu-liniate, lonidamidem various anticancer drugs, to collapse mitochondrial membrane potential and activate mitochondrial apoptotic pathway [Pg.334]