Evaluation of Chemical-Induced Oxidative Stress as a Mechanism of Hepatocyte Death
Any model of cell death should include a role for calcium ions; whether calcium ions are important initiators of cell death is uncertain. Assuming that chemical-induced injury must occur initially, then the potential for alteration of calcium ion homeostasis to contribute to cell death is very great. Almost every aspect of cell function is associated in some manner with the status and functions of calcium ions. Again, what is much less certain is the role of the various major compartments for calcium ion sequestration in the events associated with cell injury. For example, with normal physiologic conditions, liver mitochondria do not appear to have a major role in the control of intracellular calcium ion concentrations. However, under pathologic conditions, the loss of calcium storage ability by other sites in the cell will cause the mitochondria to become highly involved in the uptake of calcium ions and may even initiate calcium recycling. Whether calcium ion recycling occurs or not, the ability of mitochondria to take up calcium ions is enormous and has the potential of major alterations in not only the inner membrane potential but also the availability of a protonmotive force for ATP synthesis, ion homeostasis, and other functions. Of course, loss of cellular integrity has the potential of allowing even greater amounts of calcium to be available from exogenous sources and can eliminate the ability of the cell to cope with the total amount of calcium ion that must be regulated by sequestration. Overall, the effects of oxidative stress include the potential loss of homeostasis of cellular thiols and free calcium ion regulation.