Abstract
Cadmium (Cd) is a potent neurotoxic heavy metal, known to induce oxidative stress
and membrane disturbances in brain. Proanthocyanidins (PACs), the most abundant polyphenol
class in the human diet, have protective effects on oxidative stress and other metabolic
disorders. Based on the cellular protective effect of PACs, we aimed to investigate
whether PACs could protect the neuronal cells from Cd-induced excitotoxicity. The
experiment was carried out on mice model and also in primary culture of hippocampal
neurons isolated from neonatal mice. The Cd-induced changes in acetylcholinesterase
(AChE) activity, oxidative stress markers (lipid peroxidation/lipid hydroperoxidation),
antioxidant status and Akt phosphorylation were measured in the mice brain with or
without PACs treatment. Mice intoxicated with cadmium (5 mg/kg/day) for 4 weeks had
significantly (p<0.05) reduced the AChE levels, elevated the levels of oxidative stress
markers along with the significant (p<0.05) decrease in the levels of both enzymatic
antioxidants and non-enzymatic antioxidants in mice brain tissue. In contrast, administration
of PACs (100 mg/kg/day) for 4 weeks in cadmium-intoxicated mice had significantly
(p<0.05) protected the cadmium-mediated changes. In addition, PACs treatment in cultured
mice hippocampal neurons had protected Cd-induced excitotoxicity by activating Akt
phosphorylation, decreasing the caspase-3 level and improving the neuronal cell survival
rate up to 24 h. Altogether, our data suggest that PACs plays a crucial role on neuroprotection
in combating the cadmium induced oxidative neurotoxicity in mice brain by influencing
the activation of AChE/Akt phosphorylation, antioxidant status, controlling the membrane
damage (lipid peroxidation) and apoptotic protein caspase-3.
Key words
cadmium - proanthocyanidins - acetylcholinesterase - oxidative stress
