Involvement of glutamate, oxidative stress and inducible nitric oxide synthase in the convulsant activity of ciprofloxacin in mice

Abdel-Zaher, Ahmed O.; Afify, Abdel-Halim M.; Kamel, Sohair M.; Farghaly, Hanan S.M.; El-Osely, Gehan M.; El-Awaad, Ehab

doi:10.1016/j.ejphar.2012.04.007

Cited by 11 publications

(6 citation statements)

References 47 publications

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“…Glutamate release due to NOS activation might be the underlying mechanism 52. In one study, median convulsive dose of ciprofloxacin was increased by AG and decreased with L-arginine, suggesting that elevation of brain glutamate is the consequence of iNOS activation 53. In consistent with the above evidence, our data also revealed that iNOS inhibition could potentiate the anticonvulsive effects of the COX/5LOX inhibitor licofelone on SE induced by lithium-pilocarpine.…”

Section: Discussionsupporting

confidence: 85%

Anticonvulsive Effects of Licofelone on Status Epilepticus Induced by Lithium-pilocarpine in Wistar Rats: a Role for Inducible Nitric Oxide Synthase

et al. 2016

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Background and PurposeStatus epilepticus (SE) is a neurological disorder with high prevalence and mortality rates, requiring immediate intervention. Licofelone is a cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibitor, which its effectiveness to treat osteoarthritis has been approved. Increasing evidence suggests an involvement of COX and LOX enzymes in epileptic disorders. Thus, in the present study we investigate possible effects of licofelone on prevention and termination of SE. We also evaluated whether the nitrergic system could participate in this effect of licofelone.MethodsWe have utilized lithium-pilocarpine model of SE in adult Wistar rats to assess the potential effect of licofelone on seizure susceptibility. Licofelone was administered 1 h before pilocarpine. To evaluate probable role of nitric oxide (NO) system, L-arginine (60 mg/kg, i.p.), as a NO precursor; L-NAME (15 mg/kg, i.p.), as a non-selective nitric oxide synthase (NOS) inhibitor; aminoguanidine (100 mg/kg, i.p.), as an inducible NOS (iNOS) inhibitor and 7-nitroindazole (60 mg/kg, i.p.), as a neuronal NOS inhibitor were injected 15 min before licofelone. Also, licofelone and diazepam 10 mg/kg were administered 30 minutes after onset of SE.ResultsPre-treatment with licofelone at the dosage of 10 mg/kg, significantly prevented the onset of SE in all subjects (p < 0.001). L-arginine significantly inverted this anticonvulsant effect (p < 0.05). However, L-NAME and aminoguanidine, potentiated the anticonvulsant effect of licofelone (p < 0.05, p < 0.01). Licofelone could not terminate seizures after onset which was terminated by diazepam.ConclusionsOur findings showed that anticonvulsive effects of licofelone on SE could be mediated by iNOS. Also, we suggest that COX/5-LOX activation is possibly required in the initial stage of onset but SE recruits extra excitatory pathways with prolongation.

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Section: Discussionsupporting

confidence: 85%

Anticonvulsive Effects of Licofelone on Status Epilepticus Induced by Lithium-pilocarpine in Wistar Rats: a Role for Inducible Nitric Oxide Synthase

et al. 2016

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“…Also focal gliosis with congested blood vessels in striatum in ciprofloxacin treated rats under dose equivalent to the human therapeutic onewas noted. Recently, Abdel-Zaher et al (2012) suggested that elevation of brain glutamate levels with consequent oxidative stress and increase in the expression and activity of brain inducible NO synthase may play a pivotal role in ciprofloxacin-induced convulsive seizures. Delgado-Escueta (1984) demonstrated that the increased activity in noradrenergic, dopaminergic, and serotonergic systems are believed to reduce cortical excitability and decrease seizure activity.…”

Section: Discussionmentioning

confidence: 99%

The neuroprotective role of Nigella sativa extract on ciprofloxacin and pentylenetetrazole treated rats

Abdel-Rahman¹

2013

Afr. J. Pharm. Pharmacol.

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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.

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“…In our study, we focused on CPF primarily because clinical observations have demonstrated that quinolone antibiotics can induce seizures (Slavich et al, 1989;Springuel, 1998;Kisa et al, 2005;Striano et al, 2007;Sutter et al, 2015). This phenomenon has also been corroborated in animal experiments, such as mice and zebrafish (Abdel-Zaher et al, 2012;Arafa et al, 2013;Sivarajan and Ramachandran, 2023). In fact, the research on the mechanism of antibiotic-induced epilepsy has been investigated for decades, which can be traced back to the 1990s.…”

Section: Discussionmentioning

confidence: 90%

Gut microbiota and serum metabolomic alterations in modulating the impact of fecal microbiota transplantation on ciprofloxacin-induced seizure susceptibility

Zou,

Li,

Zou

et al. 2024

Front. Microbiol.

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IntroductionThe gut microbiota and the microbiota-gut-brain axis have gained considerable attention in recent years, emerging as key players in the mechanisms that mediate the occurrence and progression of many central nervous system-related diseases, including epilepsy. In clinical practice, one of the side effects of quinolone antibiotics is a lower seizure threshold or aggravation. However, the underlying mechanism remains unclear.MethodsWe aimed to unravel the intrinsic mechanisms through 16S rRNA sequencing and serum untargeted metabolomic analysis to shed light on the effects of gut microbiota in ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models.ResultsWe observed that ciprofloxacin treatment increased seizure susceptibility and caused gut dysbiosis. We also found similar changes in the gut microbiota of rats with lithium pilocarpine-induced epilepsy. Notably, the levels of Akkermansia and Bacteroides significantly increased in both the ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. However, Marvinbryantia, Oscillibacter, and Ruminococcaceae_NK4A214_group showed a coincidental reduction. Additionally, the serum untargeted metabolomic analysis revealed decreased levels of indole-3-propionic acid, a product of tryptophan-indole metabolism, after ciprofloxacin treatment, similar to those in the plasma of lithium pilocarpine-induced epilepsy in rats. Importantly, alterations in the gut microbiota, seizure susceptibility, and indole-3-propionic acid levels can be restored by fecal microbiota transplantation.ConclusionIn summary, our findings provide evidence that ciprofloxacin-induced seizure susceptibility is partially mediated by the gut microbiota and tryptophan-indole metabolism. These associations may play a role in epileptogenesis, and impacting the development progression and treatment outcomes of epilepsy.

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Involvement of glutamate, oxidative stress and inducible nitric oxide synthase in the convulsant activity of ciprofloxacin in mice

Cited by 11 publications

References 47 publications

Anticonvulsive Effects of Licofelone on Status Epilepticus Induced by Lithium-pilocarpine in Wistar Rats: a Role for Inducible Nitric Oxide Synthase

Anticonvulsive Effects of Licofelone on Status Epilepticus Induced by Lithium-pilocarpine in Wistar Rats: a Role for Inducible Nitric Oxide Synthase

The neuroprotective role of Nigella sativa extract on ciprofloxacin and pentylenetetrazole treated rats

Gut microbiota and serum metabolomic alterations in modulating the impact of fecal microbiota transplantation on ciprofloxacin-induced seizure susceptibility

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