Figure 1515

Covalent and noncovalent binding versus oxidative stress mechanisms of cell injury. Nephrotoxicants are generally thought to produce cell injury and death through one of two mechanisms, either alone or in combination. In some cases the toxicant may have a high affinity for a specific macromolecule or class of macromole-cules that results in altered activity (increase or decrease) of these molecules, resulting in cell injury. Alternatively, the parent nephro-toxicant may not be toxic until it is biotransformed into a reactive intermediate that binds covalently to macromolecules and in turn alters their activity, resulting in cell injury. Finally, the toxicant may increase reactive oxygen species in the cells directly, after being bio-transformed into a reactive intermediate or through redox cycling. The resulting increase in reactive oxygen species results in oxida-tive damage and cell injury.

Plasma RSG

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