Description:
<jats:title>Abstract</jats:title><jats:p>
Caenorhabditis elegans is an established model organism in
neurodegeneration and aging research. Oxidative stress and formation of advanced
glycation endproducts (AGEs), as they occur under hyperglycemic conditions in
diabetes mellitus, contribute to neuronal damage and lifespan reduction.
Sulforaphane (SFN) is an indirect antioxidant, alpha-tocopherol (vitamin E) is a
direct antioxidant that acts as a free radical scavenger. Aim of this study is
to investigate the protective effects of SFN and vitamin E against glucotoxic
damages to the neuronal system and lifespan in C. elegans. Culture
conditions that mimic clinical hyperglycemia increased the formation of reactive
oxygen species (ROS) (p<0.001) and the accumulation of
methylglyoxal-derived advanced glycation endproducts (MG-derived AGEs)
(p<0.01) with subsequent neuronal damage and neuronal
dysfunction, ultimately leading to a significant shortening of lifespan
(p<0.01). Treatment with both, 20 µmol/l SFN
and 200 µg/ml vitamin E, completely prevented the increase in
ROS and MG-derived AGEs, abolished the glucotoxic effects on neuronal structure
and function, and preserved lifespan, resulting in a life expectancy similar to
untreated controls. These data emphasize the relevance of indirect and direct
antioxidants as potential therapeutic options for the prevention of glucotoxic
pathologies.</jats:p>