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Hippocampus and amygdala neurotoxicity produced by systemic lidocaine in adult rats.

Blas-Valdivia V, Cano-Europa E, Hernández-García A, Ortiz-Butrón R

Departamento de Fisiología "Mauricio Russek Berman", Escuela Nacional de Ciencias Biológicas, I.P.N., Carpio y Plan de Ayala, D.F., C.P.11340, México.

There is evidence that using lidocaine-treated cellular culture produces cell damage. However, there are no studies in vivo demonstrating the potential injurious effect of lidocaine on the central nervous system. Therefore, the aim of our study was to investigate if lidocaine is involved in neuronal damage in the CA3 hippocampus and amygdala regions when using a single subconvulsive or a convulsive lidocaine dose. Two-month-old male Wistar rats (57) were used. The animals were randomly assigned to one of three groups. Group I received 0.9% saline ip (n=9), group II received a single lidocaine dose of 60 mg/kg (n=18), and group III received 90 mg/kg ip (n=12). At day 2, 7, and 10 after the dosing, three to six rats per group were sacrificed. The brains of the rats were removed and were embedded in paraffin. Coronal cuts of 7 mum were made. Each brain section was stained with cresyl-eosin. We evaluated the number of normal and abnormal neurons in the hippocampal CA3 (pyramidal) and basolateral amygdala (large and medium neurons) regions in a 10,000 mum(2) section. To explore an association between lidocaine-induced seizure and neuronal damage, diazepam was used (10 mg/kg ig) as an anticonvulsant two hours before a 90 mg/kg dose of lidocaine. Lidocaine causes a morphological neuronal alteration in the CA3 hippocampal region and the basolateral amygdala and possibly an inhibition-excitation imbalance. Diazepam prevents lidocaine-induced seizures, but not neuronal damage in brain structures. Interaction of lidocaine with the membrane components produces disrupted Ca(+2) homeostasis and causes neuronal damage. Moreover, it is possible that lidocaine or its metabolites could actively participate in the neuronal damage observed.

Published 24 August 2007 in Life Sci, 81(8): 691-4.
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