Glutamate mediated intracellular calcium accumulation and free radical generation are thought to be major mechanisms that contribute to cell death in hypoxic-ischemic brain injury. For this reason, various glutamate receptor antagonists and antioxidants have been investigated for their therapeutic potential. To assess whether L-carnitine, a possible antioxidant, is able to prevent glutamate- and kainic acid (KA)induced neurotoxicity. Glutamate (10(-7) M) and one of its receptor agonists, KA (10(-4) M) were administered to cerebellar granular cell cultures that were prepared from I-day-old Sprague-Dawley rats. The neuroprotective effect Of L-carnitine was examined. L-carnitine at doses of 10(-6), 10(-5), 10-4, 10(-3) M was applied to culture flasks. L-carnitine at doses of 10(-4) and 10(-3) M significantly blocked glutamate-induced neurotoxicity. 10(-4) M dose Of L-carnitine proved to be more effective than 10(-3) M. L-carnitine also blocked KA-induced neurotoxicity only at the dose of 10(-4) M. 10(-4) M L-carnitine, the most effective dose in both glutamate- and KA-induced neurotoxicity, decreased glutamate-induced neuronal cell death from 36.14 +/- 2.95% to 17.59 +/- 2.25%; (P < 0.001) and KA-induced neuronal cell death from 21.4 +/- 0.41 to 13.4 +/- 1.38%; (P < 0.001). The present study demonstrates that L-carnitine protects against glutamate- and KA-induced neurotoxicity. Protective effect Of L-carnitine may result from its antioxidant activity because free radical generation is a common result in either glutamate- or KA-induced neurotoxicity. L-carnitine merits further investigation as a therapeutic option in hypoxic-ischemic brain injury of newborn. (c) 2005 Elsevier B.V. All rights reserved.