Estudo do potencial convulsivante de compostos carbapenêmicos em modelo de convulsão induzido por pilocarpina in vivo e in vitro

Abstract

Infectious diseases of bacterial etiology have always been a serious problem for societies, not only because of their easy and rapid spread, but also because of the high mortality they cause. Treatment of these infections requires the therapeutic use of antibiotics. Carbapenems are antimicrobial drugs belonging to the β-lactam group and act by inhibiting bacterial cell wall synthesis. Treatment with these drugs can trigger several adverse effects such as nausea, rash, leucopenia, thrombocytopenia, nephrotoxicity and neurotoxicity. The risk of neurotoxicity is inherent in all class representatives, but seizure incidence may vary between drugs. This study aimed to study the effects of carbapenems (imipenem, meropenem and ertapenem) on pilocarpine induced seizure in mice. Male Swiss mice (28-34g) were pretreated with these antimicrobials at doses of 100mg / kg and 200mg / kg for 7 days. Two hours after the last dose of each drug, seizure was induced in all animals by the administration of pilocarpine 400 mg / kg ip. In the behavioral analysis, the times for the first seizure and death were recorded and, after the tests , Three brain areas (pre-frontal cortex, hippocampus and striatum) were dissected to determine the degree of lipid peroxidation, malondialdehyde concentration (MDA), nitrite concentration and the participation of the antioxidant defense glutathione reductase (GSH). Data were analyzed by ANOVA and Student-Newman-Keuls as post-test. All antibiotics were found to reduce seizure and death latencies at doses of 100 and 200 mg / kg with significance (p <0.001). Regarding the parameters of oxidative stress, there was an increase in MDA levels in all areas of the groups treated with antimicrobials at doses of 100 and 200 mg / kg, however, the groups receiving pilocarpine increased in all areas only At the dose of 200mg / kg. Nitrite concentration is also elevated in most areas at doses of 100 and 200 mg / kg and in groups receiving pilocarpine. A reduction in GSH concentration was observed in all areas of the antimicrobial groups at doses of 100 and 200 mg / kg relative to the healthy group. Therefore, our findings corroborate with the pro-convulsive activity of these antimicrobials already described in other studies, however, we suggest a participation of cholinergic mechanisms not previously described.