5-Fluorouracil exacerbates cefepime-induced convulsions in pentylenetetrazol-kindled mice.
Epilepsy Res
; 157: 106195, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31493671
ABSTRACT
OBJECTIVE:
The antibiotics cefepime and meropenem are recommended for the treatment of neutropenia. However, cefepime has been found to be associated with both peripheral and central adverse events such as renal impairment and seizures, respectively. Previous studies showed that cefepime exacerbated convulsions in corneal kindled mouse models of epilepsy. However, its involvement in chemotherapy-induced side effects is unknown.METHODS:
In this study, we examined the convulsive potential of cefepime (500â¯mg/kg) and meropenem (500â¯mg/kg) in pentylenetetrazol (PTZ)-kindled mice using an electroconvulsive shock test with low-intensity stimulus currents. Then, the effects of 5-fluorouracil (5-FU, 200 and 400â¯mg/kg, i.p.) treatment, a model of chemotherapy-induced side effects, were investigated in the PTZ-kindled mouse model.RESULTS:
In fully PTZ-kindled mice, intravenous administration of cefepime (500â¯mg/kg) or meropenem (500â¯mg/kg) did not elicit any convulsions in the electroconvulsive shock test with low-intensity stimulus currents. In the PTZ-kindled mice treated with 5-FU (200â¯mg/kg), intravenous administration of cefepime (500â¯mg/kg) exacerbated the convulsions that occurred within 1â¯min in the electroconvulsive shock test, and the mice subsequently developed convulsive status epilepticus. However, intravenous administration of meropenem (500â¯mg/kg) did not produce such effects.CONCLUSION:
These findings suggest that the combination of 5-FU and cefepime exacerbates early-onset convulsive seizures and elicits delayed-onset convulsive status epilepticus. Additionally, 5-FU treatment increases the risk of induction of neurotoxic side effects by cefepime.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Pentilenotetrazol
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Convulsões
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Convulsivantes
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Fluoruracila
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Cefepima
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Excitação Neurológica
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Antibacterianos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article