Suppressive effect of orally administered copper(II)‐aspirinate (Cu₂(asp)₄) complex on the generation of reactive oxygen species in the skin of animals subjected to UVA exposure

<jats:p><jats:bold>Abstract: </jats:bold> As reactive oxygen species (ROS) are involved in the pathogenesis of various diseases, superoxide dismutase (SOD) and its mimetic complexes have been intensively studied. Recently, we found that Cu<jats:sub>2</jats:sub>(aspirinate)<jats:sub>4</jats:sub> (Cu<jats:sub>2</jats:sub>(asp)<jats:sub>4</jats:sub>) has both <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic> antioxidative activities. We investigated the suppressive effect of Cu<jats:sub>2</jats:sub>(asp)<jats:sub>4</jats:sub> on ROS generation in the skin of hairless mice that were orally administered Cu<jats:sub>2</jats:sub>(asp)<jats:sub>4</jats:sub> and followed by UVA exposure. The results were compared with those obtained from mice that were orally administered Cu(salicylate)<jats:sub>2</jats:sub> (Cu(sal)<jats:sub>2</jats:sub>) or Cu(acetate)<jats:sub>2</jats:sub>, (Cu(ace)<jats:sub>2</jats:sub>) and followed by UVA exposure. After confirming that Cu<jats:sub>2</jats:sub>(asp)<jats:sub>4</jats:sub> suppressed ROS generation in the skin, we measured both SOD activity and metallothionein (MT) and SOD protein levels in the whole proteins extracted from the skin of ICR mice that were orally administered Cu(II) compounds. The Cu<jats:sub>2</jats:sub>Zn<jats:sub>2</jats:sub>‐SOD activity was enhanced by the administration of Cu(II) compounds; however, no alterations in the protein levels of MT and SOD were observed. Metallokinetics of the paramagnetic Cu(II) species in the circulating blood of rats, as estimated by electron spin resonance (ESR), revealed that among the Cu(II) compounds, the residence time of the Cu(II) species from Cu<jats:sub>2</jats:sub>(asp)<jats:sub>4</jats:sub> was the longest. On the basis of these results, we conclude that Cu<jats:sub>2</jats:sub>(asp)<jats:sub>4</jats:sub> is an orally potent antioxidative compound that suppresses ROS generation in the skin. The residence time of Cu(II) in the blood and the enhanced SOD activity in the skin following the oral administration of Cu<jats:sub>2</jats:sub>(asp)<jats:sub>4</jats:sub> support this conclusion. Here, we propose that Cu<jats:sub>2</jats:sub>(asp)<jats:sub>4</jats:sub> may be used to protect the skin against ROS generation.</jats:p>