Indexed on: 11 Jul '06Published on: 11 Jul '06Published in: European Journal of Pharmacology
We sought to determine the changes in brain interleukin-1beta (IL-1beta) following the coadministration of norfloxacin (25 mg/kg, i.p.) with biphenylacetic acid (100 mg/kg, p.o.) in rats. Norfloxacin provoked clonic convulsions in rats treated concomitantly with biphenylacetic acid, a major metabolite of the nonsteroidal anti-inflammatory drug fenbufen. Seizure activity was analyzed by EEG monitoring. Behavioral changes were also monitored. IL-1beta expressions in the prefrontal cortex and hippocampus at different time intervals were studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The epileptiform discharges appeared in all the rats, accompanied with limb twitching and clonic-tonic seizures after administration of norfloxacin coadministered with biphenylacetic acid. Norfloxacin plus biphenylacetic acid-induced convulsions rapidly and transiently enhanced IL-1beta mRNA in the prefrontal cortex and hippocampus. IL-1beta mRNA expression in the prefrontal cortex and hippocampus was detected as soon as 30 min after norfloxacin injection, and decayed to control levels by 6 h. ELISA analysis revealed significant increase of the IL-1beta protein in the prefrontal cortex and hippocampus at 2 h and 6 h. Administration of either norfloxacin or biphenylacetic acid alone did not elicit convulsions and increase in IL-1beta mRNA and protein expressions. The results suggest that the increased IL-1beta expressions in the prefrontal cortex and hippocampus induced by norfloxacin with biphenylacetic acid relate to seizure activities, and that these brain regions play pivotal roles in norfloxacin-induced convulsions.