There is growing evidence that glutamate receptor-mediated injury plays a crucial role in bilirubin neurotoxicity. L-carnitine (LC) has been shown to prevent glutamate-induced toxicity in neuronal cell culture. The purpose of this study is to assess whether LC is able to prevent bilirubin neurotoxicity. Unconjugated bilirubin at different concentrations was administered to cerebellar granular cell cultures prepared from 1-day-old Sprague-Dawley rats. The neuroprotective effect of LC was examined. LC at doses of 10(-6), 10(-5), 10(-4) and 10(-3) M was applied to culture flasks. LC at a dose of 10-4 M Significantly blocked bilirubin neurotoxicity. On the other hand, LC significantly increased bilirubin toxicity at a higher dose (10(-3) M). LC at the doses of 10(-5) and 10(-6) M was found to be ineffective. 10(-4) M LC decreased bilirubin-induced neuronal cell death from 47.72 +/- 3.68 to 27.23 +/- 5.14%, (P = 0.003). The present study demonstrates, for the first time, that LC protects against bilirubin neurotoxicity in a dose-dependent manner in cerebellar granular cell culture of rats. Further research is needed to confirm our findings and to clarify the mechanisms responsible for the protective effect of LC. (c) 2006 Elsevier B.V. All rights reserved.