Glyoxal (GO) and
methylglyoxal (MGO) cause
protein and
nucleic acid carbonylation and oxidative stress by forming reactive
oxygen and carbonyl species which have been associated with toxic effects that may contribute to
cardiovascular disease, complications associated with
diabetes mellitus, Alzheimer's and
Parkinson's disease. GO and MGO can be formed through oxidation of commonly used reducing
sugars e.g.,
fructose under chronic hyperglycemic conditions. GO and MGO form
advanced glycation end products which lead to an increased potential for developing inflammatory diseases. In the current study, we have investigated the protective effects of
ferulic acid and related
polyphenols e.g.,
caffeic acid,
p-coumaric acid,
methyl ferulate,
ethyl ferulate, and
ferulaldehyde on GO- or MGO-induced cytotoxicity and oxidative stress (ROS formation, protein carbonylation and mitochondrial membrane potential maintenance) in freshly isolated rat hepatocytes. To investigate and compare the protective effects of
ferulic acid and related
polyphenols against GO- or MGO-induced toxicity, five hepatocyte models were used: (a) control hepatocytes, (b) GSH-depleted hepatocytes, (c)
catalase-inhibited hepatocytes, (d)
aldehyde dehydrogenase (ALDH2)-inhibited hepatocytes, and (e) hepatocyte
inflammation system (a non-toxic H2O2-generating system). All of the
polyphenols tested significantly decreased GO- or MGO-induced cytotoxicity, ROS formation and improved mitochondrial membrane potential in these models. The rank order of their effectiveness was caffeic acid∼ferulaldehyde>
ferulic acid>
ethyl ferulate>
methyl ferulate>
p-coumaric acid.
Ferulic acid was found to decrease protein carbonylation in GSH-depleted hepatocytes. This study suggests that
ferulic acid and related
polyphenols can be used therapeutically to inhibit or decrease GO- or MGO-induced hepatotoxicity.