L-Carnitine Protects Against Glutamate- and Kainic Acid-Induced Neurotoxicity in Cerebellar Granular Cell Culture of Rats

Abstract

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 1-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. © 2005 Elsevier B.V. All rights reserved.