Mechanisms involved in the protective effect of carotenoids, polyphenols and sex hormones on human primary skin cells under oxidative stress

Skin ageing is influenced by several factors including environmental exposure and hormonal changes. Reactive oxygen species (ROS), which mediate many of these effects, can be formed by extrinsic factors, such as sun exposure, or can result from mitochondrial dysfunction as occurs during ageing. Several studies have shown the protective role of estrogens and various phytonutrients on skin health. The aim of the current study was to examine the damage to dermal fibroblasts due to mitochondrial dysfunction, and to study the protective effects of carotenoids, polyphenols, and estradiol. Rotenone, a complex I inhibitor, was used to cause mitochondrial dysfunction in human dermal fibroblasts and its effects on ROS levels, cell death, apoptosis, MMP1 and pro-collagen secretion were determined as markers of skin damage. Rotenone increased mitochondrial and cytosolic ROS which led to increased NFƙB and AP-1 transcriptional activity, apoptotic cell death, upregulation of MMP1 secretion and decreased collagen secretion. Pretreatment with carotenoid rich tomato extract, rosemary extract and estradiol reduced mitochondrial and cytosolic ROS level and MMP1 secretion and increased cell number and SIRT1 expression. These effects can be partially explained by inhibiting caspase 3 activity and by synergistically increasing ARE/Nrf2 activity and by upregulation of antioxidant proteins such as NQO-1 and Trxr1, and the decreased expression of MAPK2/3 and decreased activity of NFƙB and AP-1 transcriptional activities by decreasing c-jun and c-fos expression. This study indicates that phytonutrients and estradiol protect skin cells from damage caused by mitochondria generated ROS and thus, may delay skin aging and improve skin health.