Figure 13 - uploaded by Nadia Mohamed Said Arafa
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Fourteen days gati showing congestion of blood vessels and capillaries of the cerebral cortex with perivascular oedema (V) and diffuse gliosis (arrow). (H and E x-64).
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The objective of the present work is to study the possible role of neurotransmitters in the central nervous system (CNS) side effects due to the administration of ciprofloxacin (80 mg/kg body weight) and gatifloxacin (32 mg/kg body weight) in male albino rats for 3, 7 and 14 days.The frontal cortex of ciprofloxacin and gatifloxacin treated groups r...
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... The selection of the doses of ciprofloxacin, extract, and valproate was based on previous studies (Ajiboye et al. 2017;Rawi et al. 2011;Sveberg et al. 2002). Valproate was chosen as the reference drug because of its accessibility in the hospital and low toxicity. ...
... Ciprofloxacin-mediated decrease in brain acetylcholine has been reported (Sieb 1998). Consistent with Rawi et al. (2011), the activity of acetylcholinesterase in brains of ciprofloxacin-treated rats increased significantly. These alterations suggest impaired cholinergic neurons and could limit the availability of acetylcholine, an excitatory neurotransmitter, and influence neuromodulation (Picciotto et al. 2012). ...
Phyllanthus muellarianus (Kuntze) Exell. (Euphorbiacea) leaves are widely used in the treatment of neurological disorders in Nigeria. We investigated the protective effect of aqueous leaf extract of Phyllanthus muellarianus on ciprofloxacin neurotoxicity in male rats. Control rats (Group A) received distilled water, Groups C–E According to the Animal grouping and treatment section, Group B did not receive P. muellarianus> rats were administered 100, 200, and 400 mg/kg body weight P. muellarianus, respectively, and Group F rats received 200 mg/kg body weight valproate orally for 7 days. In addition, groups B–F rats were orally administered ciprofloxacin for 7 days. Motor coordination and motor function were assessed using narrow beam and landing foot splay distance. The levels of neurotransmitter and oxidative stress biomarkers were also determined. Aqueous leaf extract of P. muellarianus significantly attenuated ciprofloxacin-mediated increases in narrow beam, landing foot splay distance, and gait scores. Ciprofloxacin-mediated depletion of acetylcholine and dopamine in the brains of rats was significantly annulled by P. muellarianus. Furthermore, the extract significantly reversed ciprofloxacin-mediated increases in acetylcholinesterase, monoamine oxidase A, and monoamine oxidase B by 73.13%, 71.52%, and 86.54%, respectively. The altered biomarkers of oxidative stress were significantly reversed by P. muellarianus. Overall, the results of this study show that P. muellarianus reversed ciprofloxacin-induced neurotoxicity by restoring ciprofloxacin-mediated alterations in acetylcholine, dopamine, acetylcholinesterase, monoaminergic enzymes, and oxidative stress biomarkers in the brains of rats.
... The characteristics of gatifloxacin transport across blood brain barrier were investigated using primary cultured rat brain microvessel endothelial cells (rBMECs) as an in vitro model and study suggested that gatifloxacin transport across rBMECs involves a Na+/Ca 2+ exchange mechanism and extracellular Ca 2+ (Li et al., 2009). The effect on Ca 2+ may declare the effect of both antibiotics on taurine levels detected favoring recovery after neuronal hyperactivity (Rawi et al., 2011). Elevated aspartate, serine and glycine might suggest to the excitatory potencies of fluoroquinolones through their activation role on N-Methyl-D-aspartate-type glutamate receptor (NMDAR) (Curras and Dingledine, 1992;Wolosker, 2006;Wolosker et al., 2008). ...
... Biochemical studies proposed role for AChE in brain mechanisms in development of status epilepticus through decrease in the AChE activity in the hippo-campus (Freitas et al., 2006). The effect of ciprofloxacin and gatifloxacin on GABA levels and acetyl-echolinesterase activities in cortex and hippocampus and their relation to anixiety and seizure generation was discussed in our previous study (Rawi et al., 2011;Abdel-Rahman et al., 2013). Seizure induction or decrease seizure threshold related effect to either ciprofloxacin or gatifloxacin single dose was previously declared (Darwish, 2008;Quigley and Lederman, 2004). ...
... So the increment in the intracellular Ca 2+ ions led to the rupture of the vesicles in the presynaptic terminals and increased the release of the neurotransmitters (Bullock et al., 1995) as a result, the content of catecholamine is decreased. The neurotransmitters alterations support the hyperexcitability which reflected on the histopathology of cortex and hippocampus mainly in the most affected Gati group in line with several previous studies discussed in Rawi et al. (2011) and Arafa et al. (2013). ...
The study aimed to evaluate the neurotoxicity of ciprofloxacin (Cip) or gatifloxacin (Gati) single oral dose in male albino rats weighing (100±20g) grouped as control-administered water, ciprofloxacin (80mg/kg) and gatifloxacin (32mg/kg) each of 12 rats.
The frontal cortex of both groups revealed decrease in glutamate, GABA, taurine, histidine and serotonin levels and elevation of aspartate, glycin and serine and AChE activities. While, noradrenaline and dopamine levels reduced significantly in Gati group, noradrenaline increased significantly in Cip group. Hippocampus of either Cip or Gati group's results revealed elevation of all detected amino acids and monoamines except the reduction of glutamate, aspartate and dopamine in Cip group. In the meantime, AChE activities significantly reduced in both treatments. Serum results showed elevation of glucose in both treated groups. The histological examination of Gati brain tissue showed neuronal degeneration in the cerebral cortex and congestion in the blood vessels and capillaries in hippocampus tissue without histopathological alteration observed in Cip group tissue.
Overall, the data showed the effect of the quinolones single dose towards hyperglycemia and shift in balance of neurotransmitters and acetylcholinesterase as well as the histopathological alterations in the tested brain areas.
Key words: Ciprofloxacin; Gatifloxacin; Cortex; Hippocampus; Neurotransmitters; Glucose.
... Therefore, all ACh released in the synaptic cleft would only bind to ChE such that its activity would increase. Moreover, fluoroquinolones could act as cholinergic agonists or modify the gene coding for choline acetyl-transferase, leading to an increase of ACh production (Rawi et al., 2011), which would be further hydrolysed by ChE resulting in a significant increase of the enzymatic activity. ...
... Ciprofloxacin administration in a less vigorous extent as regard with PTZ results also decreased the acetylcholinesterase activities and monoamines levels in the investigated brain areas which support the proconvulsant effect of the quinolones previously discussed in Smolders et al. (2002) and Rawi et al. (2011). Ciprofloxacin may decrease the threshold of epileptogenic activity (Agbaht et al., 2009) where, ciprofloxacin induced seizures in healthy patients (Darwish, 2008). ...
... Ciprofloxacin may decrease the threshold of epileptogenic activity (Agbaht et al., 2009) where, ciprofloxacin induced seizures in healthy patients (Darwish, 2008). Extensive toxicological and biochemical experiments have been performed to explain the CNS side effects observed under therapeutic conditions (Stahlmann and Lode, 1999;Rawi et al., 2011). Bidziński et al. (1998) concluded that there is a functional interaction between brain serotonin and GABA systems, due to the effect of serotonin depletion in GABAA receptor down-regulation. ...
... Also data recorded about monoamines in the tested antibiotic may be a supplement data to the previously mentioned seizure inducing activity of quinolones (Moorthy et al., 2008;Agbaht et al., 2009). The results of Rawi et al. (2011 and2011a) suggested a shift in the balance of antioxidant markers towards the oxidative stress in cortex, hippocampus and striatum through elevation in malondialdehyde, nitric oxide contents and superoxide dismutase enzyme activity and reduction of glutathione, glutathione peroxidase and Na+, K+, adenosine triphosphatase enzymes activity. The effect tested through histopathological examinations showed focal gliosis, hemorrhagic areas in cerebral cortex and neuronal degeneration, oedema and astrosytosis in hippocampus. ...
This study aimed to investigate the Nigella sativa seed (NS) neuroprotective effect on ciprofloxacin
(CFX) antibiotic with suggesting neurotoxic effect in rats through the determination of monoamines
levels and acetylcholinesterase (AChE) activity in different brain areas. We used valporic acid as a
reference antiepileptic drug and pentylenetetrazole (PTZ), a drug used for induction of epileptic model
in rats. The present data revealed that the daily oral administration of NS (350 mg/kg b.wt.) for 14 days
caused significant increase in the monoamines contents with no statistical difference in AChE as
compare to control values. While the administration of CFX (500 mg/kg b.wt.) and/or PTZ (60 mg/kg
b.wt.) was found to produce significant decrease in the concentration of monoamines and the activity of
AChE in cerebral cortex, cerebellum, striatum and hippocampus after 7 and 14 days. Moreover, the preand
post-treatment with NS in CFX and/or PTZ treated rats was found to ameliorate most of the side
effects induced by these drugs. It could be concluded that the treatment with the therapeutic dose of
CFX 14 days could lead to the development of seizures through the reduction of monoamines level and
decreasing the activity of AChE in the tested brain areas. The administration of N. sativa pre- and the
post treatment to CFX and/or PTZ treated rats were found to ameliorate their side effects. Suggesting
that N. sativa seeds with antiepileptic activity and its administration could alleviate ciprofloxacin
neurotoxicity.
... In addition, it has been investigated that ciprofloxacin has proconvulsant and epileptogenic effects [56,64]. Moreover, the treatment with ciprofloxacin caused an increase in the level of glycine in cerebral cortex and hippocampus [65], this result is in agreement with the finding of the present study, where the administration with ciprofloxacin was found to increase the content of glycine in most of investigated brain regions. ...
The neuroprotective effect of Nigella sativa (NS) on amino acid neurotransmitters alteration in pentylenetetrazole (PTZ) and ciprofloxacin (CFX) treated rats in different brain regions was examined. The oral administration of NS induced an elevation in aspartate and glutamate contents, whereas the levels of GABA and glycine were decreased. Furthermore, the treated groups with PTZ and CFX caused a decrease in aspartate, glutamate and total antioxidant capacity levels, while the concentrations of GABA and glycine were increased after 14 days. Moreover, the pre- and post-treatment with NS in PTZ and CFX treated rats return the levels of these parameters near control values. So, it could be concluded that the treatment with CFX induced imbalance between the excitatory and the inhibitory amino acids which may lead to the initiation of epileptic seizures and the treatment with NS was found to ameliorate these neurological defects which reflect its potent antiepileptic activity.
The increased presence of emergent compounds, such as pharmaceuticals drugs, in the aquatic compartment has been acknowledged as an evolving environmental issue whose consequences are not yet fully characterized. Specific classes of pharmaceutical drugs, such as fluoroquinolone antibiotics, can exert toxic effects to non-target species with ecological significance, since these compounds are environmentally stable and persistent, and may interact with some of the key physiologic processes of organisms. Despite such characteristics, knowledge about the effects of these drugs is still scarce, especially to non-target organisms. The present study aimed to evaluate the effects of chronic and acute exposures of the cladoceran Daphnia magna to the fluoroquinolone antibiotic ciprofloxacin. Putative toxic effects were assessed, following acute and chronic exposures to ecologically relevant concentrations of ciprofloxacin, through enzymatic (cholinesterase - ChEs, catalase - CAT, glutathione S-transferases - GSTs) and non-enzymatic (thiobarbituric acid reactive substances - TBARS, glycogen - Gly) biomarkers. In addition, we also determined behavioural (swimming distance - SD) and morphological (body length of the first brood - BL1B) endpoints in animals exposed to this drug. Ciprofloxacin acute exposure resulted in increased CAT and ChEs activities, and inhibited GSTs activity. After chronic exposure, ChEs activity was significantly inhibited, while GSTs activity was significantly enhanced. TBARS levels were only increased at higher concentrations of ciprofloxacin. CAT activity and Gly content did not evidence a clear and significant pattern of variation. SD was slightly inhibited during dark cycles. BL1B presented a significant decrease for animals subjected to an intermediate concentration. Results showed that even ecologically relevant concentrations of ciprofloxacin may cause oxidative stress in individuals of D. magna. The present study showed important data that corroborate the occurrence of significant biochemical alterations in key features of an aquatic organism when exposed to relevant levels of a widely used antibiotic, establishing essential links between environmental exposure to this specific drug and putative toxic challenges that may result in irreversible changes and damages, especially at the individual level. However, changes in the size of neonates suggest that population alterations are likely to occur under real scenarios of chronic contamination by this drug.
Fluoroquinolones are broad-spectrum antibiotics with efficacy against a wide range of pathogenic microbes associated with respiratory and meningeal infections. The potential toxicity of this class of chemical agents is a source of major concern and is becoming a global issue. The aim of this study was to develop a method for the brain distribution and the pharmacokinetic profile of gatifloxacin in healthy Sprague-Dawley rats, via Multicenter matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) and quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS). We developed a sensitive LC-MS/MS method to quantify gatifloxacin in plasma, lung, and brain homogenates. A pharmacokinetic profile was observed where there is a double peak pattern; a sharp initial increase in the concentration soon after dosing followed by a steady decline until another increase in concentration after a longer period post dosing in all three biological samples was observed. The imaging results showed the drug gradually entering the brain via the blood brain barrier and into the cortical regions from 15 to 240 min post dose. As time elapses, the drug leaves the brain following the same path as it followed on its entry and finally concentrates at the cortex. Copyright © 2015 John Wiley & Sons, Ltd.
A liquid chromatography method was developed and validated for the simultaneous determination of gatifloxacin and dexamethasone sodium phosphate in bulk and pharmaceutical formulations. Optimum separation was achieved in less than 5 min using a C 18 column (250 × 4.6 mm i.d, 5 µ particle size) by isocratic elution. UV detection was carried out at 254 nm. Developed method was economical in terms of the time taken and amount of solvent consumed for each analysis. It was also validated with respect to linearity, limit of detection, limit of quantification, precision, accuracy, specificity, robustness and system suitability. The limits of detection for gatifloxacin and dexamethasone sodium phosphate were 0.397 and 0.11 µg/ml, respectively. Limits of quantification were found to be 1.203 and 0.342 µg/ml for gatifloxacin and dexamethasone sodium phosphate, respectively. The developed method was successfully applied to the simultaneous determination of gatifloxacin and dexamethasone sodium phosphate in bulk and pharmaceutical formulations.
