Ciprofloxacin-induced neurotoxicity: evaluation of possible underlying mechanisms

Abstract

Ciprofloxacin (CPX) is a fluoroquinolone antibiotic used for treating respiratory, urinary tract, gastrointestinal and abdominal infections. There are only a limited number of studies related to neurological adverse effects of this drug in therapeutic doses. Therefore, in the present study, we aimed to investigate the influence of CPX, when administered at pharmacological doses, on behavioral parameters of rats and the probable underlying mechanisms. CPX was administered in single oral daily doses of 20 and 50mg/kg for 14 days in rats. CPX-induced depression and anxiety were evaluated by modified forced swimming test and elevated plus maze test, respectively. Also, spontaneous locomotor activity and motor coordination were assessed by activity cage and Rota-rod apparatus. Effects of CPX administration on brain serotonin, dopamine, -amino-butyric acid (GABA), glutamate, adrenaline and noradrenaline levels were determined by high performance liquid chromatography (HPLC) analysis. Contribution of oxidative stress to the changes induced by CPX administration was evaluated by measuring brain catalase, superoxide dismutase, glutathione (GSH) and malondialdehyde (MDA) levels. Our results indicated that depression-like and anxiety-like behaviors were observed only in the 50mg/kg CPX-administered group with simultaneous decreases in the brain serotonin and GABA levels. In addition, in the brain homogenates of CPX-administered groups, increased MDA as well as decreased GSH and catalase activity with respect to their controls, indicated enhanced oxidative stress and weakened antioxidant defense system. In conclusion, repeated pharmacological doses of CPX were found to induce neurological toxicity. Also, altered brain neurotransmitter levels and increased oxidative stress observed in our study were thought to be the possible underlying mechanisms of ciprofloxacin-induced neurotoxicity.