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.
Keywords
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Article info
Publication history
Accepted:
February 15,
2005
Received in revised form:
February 15,
2005
Received:
July 22,
2004
Identification
Copyright
© 2005 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
