Biochemical mechanisms of oxidative liver cell injury.

The toxicological implications of the formation of active oxygen species have attracted growing interest in recent years. Under aerobic conditions, oxygen radicals are normal cellular metabolites. However, the production of oxygen radicals may be greatly stimulated in the presence of various redox active compounds. Eventually, the stimulation of oxygen radical production may be so great as to overwhelm the cellular defence systems, create an oxidative stress and bring about toxicity. Recent studies in this laboratory indicate that glutathione and protein thiol depletion play a critical role in the development of oxidative cell injury. This depletion of cellular thiols can result in a disturbance of intracellular calcium ion homeostasis, which seems to be directly related to cell killing.