Antioxidants and herbal extracts protect HT-4 neuronal cells against glutamate-induced cytotoxicity

Abstract

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.

Bilobalide prevents apoptosis through activation of the PI3K/Akt pathway in SH-SY5Y cells

“…Cell viability was determined by a colourimetric 3-4,5-dimethyithiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT) assay according to Kobayashi et al [21]. Briefly, cells were plated into 96-well plates.…”

Antioxidants and polyunsaturated fatty acids in multiple sclerosis

“…Moreover, dietary compounds, for example, flavonoids, curcumin, NAC and vitamin E, can protect neuronal cells against glutamateinduced excitotoxicity (Kobayashi et al, 2000;Sen et al, 2000;Mazzio et al, 2001). In conclusion, dietary antioxidants and fatty acids may influence the disease process in MS by reducing immune-mediated inflammation, oxidative stress and excitotoxic damage.…”

Protective mechanisms of Pycnogenol® in ethanol‐insulted cerebellar granule cells

“…In combination and individually, these polyphenols decrease toxic byproducts of lipid peroxidation and prooxidants such as H 2 O 2 , HO⅐, OO⅐, and O 2 ⅐ Ϫ (Kobuchi et al, 1999;Packer et al, 1999;Nardini et al, 2000). Treatment with PYC inhibits programmed neuronal cell death, glutamate-induced neurotoxicity, and EtOH-induced apoptosis (Kobayashi et al, 2000;Peng et al, 2002;Siler-Marsiglio et al, 2004). Because PYC ameliorates EtOH-induced damage and death in developing neurons (Siler-Marsiglio et al, 2004), we have further investigated its protective mechanisms regarding antioxidant enzyme systems.…”