Antioxidants and herbal extracts protect HT-4 neuronal cells against glutamate-induced cytotoxicity.
Antioxidant therapy has been shown to be beneficial in neurological disorders including Alzheimer's disease and cerebral ischemia. Glutamate-induced cytotoxicity in HT-4 neuronal cells has been previously demonstrated to be due to oxidative stress caused by depletion of cellular glutathione (GSH). The present study demonstrates that a wide variety of antioxidants inhibit glutamate-induced cytotoxicity in HT-4 neuronal cells. Low concentrations of alpha-tocopherol and its analogs were highly effective in protecting neuronal cells against cytotoxicity. Purified flavonoids and herbal extracts of Gingko biloba (EGb 761) and French maritime pine bark (Pycnogenol) were also effective. We have previously shown that pro-glutathione agents can spare GSH and protect cells from glutamate insult in a C6 glial cell model. The protective effects of nonthiol-based antioxidants tested in the HT-4 line were not mediated via GSH level modulation. In contrast, protective effects of thiol-based pro-glutathione agents alpha-lipoic acid (LA) and N-acetyl cysteine (NAC) corresponded with a sparing effect on GSH levels in glutamate-treated HT-4 cells. Glutamate-induced cytotoxicity in HT-4 cells is a useful model system for testing compounds or mixtures for antioxidant activity.
Kobayashi
M S
MS
Department of Molecular and Cell Biology, University of California, Berkeley 94720-3200, USA.
Han
D
D
Packer
L
L
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D020441:Ginkgo biloba / Q000737:chemistry; D018698:Glutamic Acid / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000628:therapy; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010936:Plant Extracts; D010946:Plants, Medicinal; D051381:Rats; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology; D000096983:Ginkgo Extract
D000975:Antioxidants; D018691:Excitatory Amino Acid Antagonists; D005419:Flavonoids; D016166:Free Radical Scavengers; D018698:Glutamic Acid; D005978:Glutathione; D018696:Neuroprotective Agents; D010936:Plant Extracts; D013438:Sulfhydryl Compounds; D014810:Vitamin E; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C024070:pycnogenols