Role of Nitric Oxide in the Convulsions Following the Coadministration of Enoxacin With Fenbufen in Mice

Abstract

Effects of nitric oxide (NO) synthase inhibitors on the enoxacin-induced convulsions were examined in mice pretreated with fenbufen. 7-nitroindazole markedly suppressed the incidence of convulsions, whereas L-arginine did not modify the convulsions at all. The suppression of the convulsions by 7-nitroindazole was not reversed by the pretreatment of L-arginine. Brain NO synthase activity was significantly raised at 30 min after enoxacin when combined with fenbufen. The increased NO synthase activity was found to be suppressed by the pretreatment of 7-nitroindazole. These findings suggest that endogenous NO may be involved as a proconvulsant substance in the development of enoxacin-induced convulsions in mice pretreated with fenbufen.

Opposite caudal versus rostral brain nitric oxide synthase response to generalized seizures in a novel rodent model of reflex epilepsy

“…For example, an increase in nNOS immunoreactivity was observed by immunohistochemistry in the hippocampus in a rat model of penicillin-induced epilepsy (Ren et al, 1998). Similarly, an elevation in NOS activity in several brain regions after pentylenetetrazol (PTZ)-generated seizures has been described in both mice and rats (Kaneko et al, 2002) and in mouse whole brain minus cerebellum after coadministration of enoxacin with fenbufen (Masukawa et al, 1998). NOS activity has also been reported to rise in different rat brain areas after kainate administration or lowering of extracellular Mg 2 + concentration (Yasuda et al, 2001;Kovács et al, 2009;Swamy et al, 2011).…”

“…However, although abundant experimental research has demonstrated a functional involvement of NO in the control of epileptic phenomena, the available data are conflicting and it cannot be concluded whether this atypical messenger acts as a pro-convulsant or an anticonvulsant agent (Barbiro-Michaely et al, 2011;Hrnčić et al, 2010Hrnčić et al, , 2011Przegaliñski et al, 1996;Tutka et al, 1997;Masukawa et al, 1998;Borowicz et al, 2000;Lesani et al, 2010;Łuszczki et al, 2006, 2011Sardo et al, 2008;Itoh and Watanabe, 2009;Nieoczym et al, 2010). Besides, there is still little information available describing changes in either NOS activity or expression after repeated epileptic seizures comparing different brain regions (e.g.…”

Study of anti-inflammatory and analgesic properties of 3-benzoyl-propionic acid

“…The NO produced by the NOS enzyme plays a role in inflammation and in the neuromodulation studied extensively 33 , being part of various biological functions ranging from the formation of a protective mechanism against microorganisms, until the regulation of blood pressure and a process of neurotransmission 34 . Masukawa et al 35 consider NO as a neuronal messenger of the central nervous system and modulator of various brain functions, so that various researches relate NOS enzyme to the use of Fenbufen in potential convulsive activities in rats. Sautebin 36 demonstrated that this free radical owns regulatory anti-inflammatory activity by the constitutive forms, it means, in basal concentrations; however, when NO is generated by the inducible form of NOS enzyme (iNOS), promotes inflammation and tissue dysfunction and therefore possesses pro-inflammatory properties and deleterious which to Costa et al 37 , pro-inflammatory effects of this moiety include increased vascular permeability of inflamed tissues.…”

Quinolones

“…The mechanism underlying this interaction is not established but does not appear to be mediated via benzodiazepine receptor effects [361]. Studies have suggested that the mechanism may involve enhanced cerebral glutamate (an excitatory amino acid neurotransmitter) or nitric acid concentrations [369][370][371]. Using a pharmacodynamic model created using in vitro receptor occupancy data and in vivo human pharmacokinetic data, the combination of fenbufen with prulifloxacin or enoxacin were considered the most hazardous in terms of seizure risk [362].…”