title: 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.
authors.affiliation: Division of Neonatology, School of Medicine, Atatürk University Erzurum, Turkey.
authors.forename: Ayhan
authors.initials: A
authors.lastname: Tastekin
authors.forename: Akcahan
authors.initials: A
authors.lastname: Gepdiremen
authors.forename: Rahmi
authors.initials: R
authors.lastname: Ors
authors.forename: Mehmet
authors.initials: M
authors.lastname: Emin Buyukokuroglu
authors.forename: Zekai
authors.initials: Z
authors.lastname: Halici
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002331:Carnitine / Q000494:pharmacology* / Q000627:therapeutic use; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy; D007608:Kainic Acid / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009498:Neurotoxins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D009498:Neurotoxins; D018698:Glutamic Acid; D002331:Carnitine; D007608:Kainic Acid