Changes in brain interleukin-1beta following the coadministration of norfloxacin with biphenylacetic acid in rats.
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.
Zhang
Li-rong
LR
Department of Clinical Pharmacology, School of medicine, Zhengzhou University, Zhengzhou 450052, China.
Li
Xiao-tian
XT
Tang
Wen-lu
WL
Wang
Yong-ming
YM
Cheng
Neng-neng
NN
Chen
Bin-yan
BY
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D004569:Electroencephalography / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009643:Norfloxacin / Q000633:toxicity*; D010648:Phenylacetates / Q000633:toxicity*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors
D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D010648:Phenylacetates; D012333:RNA, Messenger; C012776:biphenylylacetic acid; D009643:Norfloxacin