Changes in brain interleukin-1β following the coadministration of norfloxacin with biphenylacetic acid in rats

We sought to determine the changes in brain interleukin-1β (IL-1β) 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-1β 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-1β mRNA in the prefrontal cortex and hippocampus. IL-1β 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-1β 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-1β mRNA and protein expressions. The results suggest that the increased IL-1β 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.