Figure 3. Hierarchical oxidative stress model explains cellular events occurring sequentially as the level of oxidative stress increases.

A mild oxidative stress activates the protective antioxidant machinery in an attempt to restore the redox equilibrium (Tier 1). Higher levels of oxidative stress activate MAPK and Nf-kB cascade of molecular events leading to pro-inflammatory responses (Tier 2). Oxidative stress beyond the tolerable limit of cells, triggers cell death pathways often manifested as increased cytosolic Ca²⁺ level, lowering of mitochondrial membrane potential, opening of mitochondrial permeability transition and cell membrane damage (Tier 3).