Characterization of quinolone antibacterial-induced convulsions and increases in nuclear AP-1 DNA- and CRE-binding activities in mouse brain.
The quinolone antibacterials enoxacin and norfloxacin (2.5 mg/kg, i.v.) provoked clonic convulsions in mice treated concomitantly with biphenylacetic acid (BPAA, 100 mg/kg, i.p.), a major metabolite of the nonsteroidal anti-inflammatory drug fenbufen. Gel-shift assays showed that enoxacin-induced convulsions resulted in increases in nuclear activator protein 1 (AP-1) DNA- and cyclic AMP responsive element (CRE)-binding activities in the cerebral cortex and hippocampus, but not in other regions, such as the cerebellum and thalamus. In contrast, ofloxacin and levofloxacin, at the same doses, in the presence of BPAA did not evoke convulsions or increase these DNA-binding activities. Administration of these quinolones and BPAA alone elicited neither convulsions nor increases in these DNA-binding activities. These results suggest that the increased nuclear AP-1 DNA- and CRE-binding activities in the cerebral cortex and hippocampus induced by quinolones with BPAA correlated with seizure activities and that these brain regions play pivotal roles in quinolone-induced convulsions.
Ito
Y
Y
Department of Pharmacology, College of Pharmacy, Nihon University, Chiba, Japan. yoshii@pha.nihon-u.ac.jp
Ishige
K
K
Aizawa
M
M
Fukuda
H
H
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D002373:Cyclic AMP Receptor Protein / Q000096:biosynthesis / Q000187:drug effects*; D004569:Electroencephalography / Q000187:drug effects; D015365:Enoxacin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009643:Norfloxacin / Q000494:pharmacology*; D010648:Phenylacetates / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000096:biosynthesis / Q000187:drug effects*
D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002373:Cyclic AMP Receptor Protein; D010648:Phenylacetates; D018808:Transcription Factor AP-1; D015365:Enoxacin; C012776:biphenylylacetic acid; D009643:Norfloxacin