Background Daily exposure of human skin to environmental insults such as solar
radiation, pollution and smoke can lead to an elevation of oxidative stress, causing
premature acceleration of skin ageing. Oxidative stress is known to disrupt
cellular metabolism, which negatively impacts the skin’s functionality at the
cellular and tissue level.
Objectives To examine the changes in cellular metabolism due to oxidative stress.
Methods Glycolysis and oxidative phosphorylation rates in human dermal fibroblasts
were monitored in real time under controlled nonlethal oxidative stress
conditions. Hydrogen peroxide was utilized as a surrogate stressor because
numerous environmental stressors as well as intrinsic ageing trigger its production.
Results Hydrogen peroxide ranging between 05 and 3 mmol L1 caused a signifi-
cant decrease in glycolytic and oxidative phosphorylation rates along with cellular
ATP levels. Nicotinamide (NAM) was found to protect dose dependently as well
as restore glycolytic rates concurrent with restoring ATP to control levels. NAM
had an effective dose–response range between 01 and 10 mmol L1
, with maximal
effects attained at 05 mmol L1
. Relative to oxidative phosphorylation,
NAM was able to provide a diminished level of protection. FK866, a known
NAM phosphoribosyltransferase inhibitor, was found to inhibit the protective
effects of NAM significantly, suggesting part of the NAM mechanism of action
involves nicotinamide adenine dinucleotide (NAD+) synthesis.
Conclusions These results support previous findings that NAM protects cellular
metabolism from oxidative stress by preferentially affecting glycolysis. Additionally,
part of its mechanism of action appears to include NAD+ synthesis.
O