Antioxidant activity elicited by low dose of caffeine attenuates pentylenetetrazol-induced seizures and oxidative damage in rats

Abstract

Although caffeine supplementation has a beneficial effect on people with neurological disorders, its implications for oxidative damage related to seizures are not well documented. Thus the aim of this study was to investigate the effects of two weeks caffeine supplementation (6mg/kg; p.o.) on seizures and neurochemical alterations induced by pentylenetetrazol (PTZ 60mg/kg i.p.). Statistical analyses showed that long-term rather than single dose caffeine administration decreased the duration of PTZ-induced seizures in adult male Wistar rats as recorded by cortical electroencephalographic (EEG) and behavioral analysis. The quantification of EEG recordings also revealed that caffeine supplementation protected against a wave increase induced by PTZ. Neurochemical analyses revealed that caffeine supplementation increased glutathione (GSH) content per se and protected against the increase in the levels of thiobarbituric acid reactive substances (TBARS) and oxidized diclorofluoresceine diacetate (DCFH-DA). Also, caffeine prevent the decrease in GSH content and Na(+), K(+)-ATPase activity induced by PTZ. Our data also showed that the infusion of L-buthionine sulfoximine (BSO; 3.2μmol/site i.c.v), an inhibitor of GSH synthesis, two days before injecting PTZ reversed the anticonvulsant effect caused by caffeine. BSO infusion also decreased GSH content and Na(+), K(+)-ATPase activity. However, it increased DCFH-DA oxidation and TBARS per se and reversed the protective effect of caffeine. Results presented in this paper support the neuroprotective effects of low long-term caffeine exposure to epileptic damage and suggest that the increase in the cerebral GSH content caused by caffeine supplementation may provide a new therapeutic approach to the control of seizure.

The Effects of Adenosinergic Modulation on Cytokine Levels in a Pentylenetetrazole-Induced Generalized Tonic-Clonic Seizure Model

“…It was shown that acute exposure to adenosine and caffeine decreases the number of spikeand-wave discharges (SWDs) in genetically epileptic rats [23,24] . An interesting study, which evaluated the effects of caffeine on PTZ-induced generalized tonic-clonic seizures, reported that acute caffeine administration does not affect the latency to first clonic seizure, the latency to generalized tonic-clonic seizure and the duration of generalized tonic-clonic seizure [11] .…”

“…Caffeine may reduce neuroinflammation by regulating the adenosine receptor-mediated modulation of glutamate release. It has been shown that while chronic caffeine consumption provides neuronal protection against epileptic damage in rats, acute high-dose caffeine has an adverse effect in the animal models of epilepsy [11] .…”

Caffeine prevents d-galactose-induced cognitive deficits, oxidative stress, neuroinflammation and neurodegeneration in the adult rat brain

“…Prasanthi et al, 2010 investigated that caffeine prevents the cholesterol-induced oxidative stress in the hippocampus of rabbit. Even at low dose of caffeine the anti-oxidant activity instigated which reduced the pentylenetetrazolinduced seizures and oxidative stress-induced disorders in the adult rats (Souza et al, 2013).…”

Adenosine A2A Receptors: Localization and Function

“…Another crucial function which appears to be regulated by adenosine A 2A receptors is epileptogenesis, as indicated by the experimental and clinical evidences showing that caffeine and theophylline, another non-selective adenosine receptor antagonist, may induce and/or aggravate seizures (Boison 2011). However, the precise role of adenosine A 2A receptors in epileptogenesis is still debated, as studies in experimental animals have demonstrated that these receptors can have either facilitatory or inhibitory effects on seizures, depending on the experimental model utilized (Ates et al 2004;Souza et al 2013;Tchekalarova et al 2010). In addition, adenosine A 2A receptors can modulate nociception, and either blockade or genetic deletion of these receptors has been shown to elevate the pain threshold in experimental models (Hussey et al 2007;Ledent et al 1997), likely by an action on central nociceptive pathways.…”