Protective Effect of Combination of Sulforaphane and Riluzole on Glutamate-Mediated Excitotoxicity

Abstract

Threohydroxyaspartate (THA) causes glutamate excitotoxicity in motor neurons in organotypic culture of rat spinal cord. Some drugs, including sulforaphane (SF) and riluzole, can protect motor neuron against excitotoxicity. It has been demonstrated that SF is a potent inducer of Phase II enzymes, while riluzole is a classic anti-glutamate agent. The objective of the current study is to investigate whether the combination of SF and riluzole is superior to either one used alone. In our study, the combination of SF with riluzole not only stimulates the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), reduced nicotinamide adenine dinucleotide phosphate (NADPH): quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1), but also reduces the extracellular accumulation of glutamate. When used at optimal doses, SF (10 microM) and riluzole (5 microM), either alone or in combination, all exert significant and similar neuroprotection, as measured by the number of motor neuron, medium malondialdehyde (MDA) level and lactate dehydrogenase (LDH) level. When used at low doses, the combination is better than each agent used alone. In conclusion, these results suggest the potential utility of combination use of SF and riluzole for protection of motor neuron against excitotoxicity.