The neuroprotective effects of ergothioneine (EGT) against cisplatin toxicity were investigated both in vitro and in vivo. For in vitro study, two types of neuronal cells, primary cortical neuron (PCN) cells and rat pheochromocytoma (PC12) cells, were incubated with EGT (0.1-10.0 μM) for 2 h followed by incubation with 0.5 μM cisplatin for 72 h. Results show that cisplatin markedly decreased the proliferation of PC12 cells and strongly inhibited the growth of axon and dendrite of PCN cells, but these effects were significantly prevented by EGT. For in vivo study, CBA mice were orally administered with 2 or 8 mg EGT/kg body weight for 58 consecutive days and were injected i.p. with 5mg cisplatin/kg body weight on days 7, 9 and 11. We found that EGT significantly restored the learning and memory deficits in mice treated with cisplatin evaluated by active and passive avoidance tests. EGT also significantly prevented brain lipid peroxidation, restored acetylcholinesterase (AChE) activity and maintained glutathione/glutathione disulfide ratio in brain tissues of mice treated with cisplatin. These results demonstrate that EGT protects against cisplatin-induced neuronal injury and enhances cognition, possibly through the inhibition of oxidative stress and restoration of AChE activity in neuronal cells.
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