Figure 7.

Hypothetical model showing differences between adult rats and mice at HA. In mice (A), the transfer of electrons in mitochondrial complexes is normal (for clarity electron supply is shown only at complex I through oxidation of NADH), resulting in normal production of superoxide (O₂•-), that can be reduced first to hydrogen peroxide (H₂O₂) and then to water by SOD_Mn and GPx. In rats (B), exposure to HA alters mitochondrial functions and reduces the activity of complexes I and/or III, leading to a reduced flow of electrons that then become available to generate O₂•-. High activity of mitochondrial SOD and GPx helps to reduce O₂•- to H₂O₂ and water, but high levels of H₂O₂ leads to accumulation of hydroxyl radicals (OH•) through the Fenton reaction. OH•, being a highly reactive ROS, causes accumulation of oxidative damage in the lung tissue, altering the alveolar architecture. High activity of complex IV might contribute to accelerate electron transfer and avoid superoxide accumulation. See text for references.