6-gingerol, a major component of ginger, has antioxidant, anti-apoptotic, and anti-inflammatory
activities. However, some dietary phytochemicals possess pro-oxidant effects as well,
and the risk of adverse effects is increased by raising the use of doses. The aim
of this study was to assess the genotoxic effects of 6-gingerol and to clarify the
mechanisms, using human hepatoma G2 (HepG2) cells. Exposure of the cells to 6-gingerol
caused significant increase of DNA migration in comet assay, increase of micronuclei
frequencies at high concentrations at 20-80 and 20-40 microM, respectively. These
results indicate that 6-gingerol caused DNA strand breaks and chromosome damage. To
further elucidate the underlying mechanisms, we tested lysosomal membrane stability,
mitochondrial membrane potential, the intracellular generation of reactive oxygen
species (ROS) and reduced glutathione (GSH). In addition, the level of oxidative DNA
damage was evaluated by immunocytochemical analysis on 8-hydroxydeoxyguanosine (8-OHdG).
Results showed that lysosomal membrane stability was reduced after treatment by 6-gingerol
(20-80 microM) for 40 min, mitochondrial membrane potential decreased after treatment
for 50 min, GSH and ROS levels were significantly increased after treatment for 60
min. These suggest 6-gingerol induces genotoxicity probably by oxidative stress; lysosomal
and mitochondrial damage were observed in 6-gingerol-induced toxicity.
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