Effects of Diclofenac Sodium on Seizure Activity in Rats with Pentylenetetrazole-Induced Convulsions.

Abstract

Epilepsy is a disease which affects between 1 and 2% of the population, and a large proportion of these people do not react to currently available anticonvulsant medications, indicating the need for further research into novel pharmacological therapies. Numerous studies have demonstrated that oxidative stress and inflammation occur during epilepsy and may contribute to its development and progression, indicating higher levels of oxidative and inflammatory parameters in experimental models and clinical patients. This research aimed to assess the impact of diclofenac sodium, a nonsteroidal anti-inflammatory medicine, on seizure and levels of oxidative stress and inflammatory biomarkers in a rat model of epilepsy triggered by pentylenetetrazole (PTZ). 60 rats were randomly allocated to one of two groups: electroencephalography (EEG) recordings or behavioral evaluation. Rats received diclofenac sodium at three various doses (25, 50, and 75mg/kg) intraperitoneally (IP) or a placebo, followed by intraperitoneal (IP) pentylenetetrazole, a powerful seizure-inducing medication. To investigate if diclofenac sodium had antiseizure properties, seizure activity in rats was evaluated using EEG recordings, the Racine convulsion scale (RCS) behaviour score, the duration of the first myoclonic jerk (FMJ), and the levels of MDA, TNF-α, and SOD. The average percentage of EEG spike waves decreased from 76.8% (placebo) to 64.1% (25mg/kg diclofenac), 55.9% (50mg/kg diclofenac), and 37.8% (75mg/kg diclofenac). FMJ had increased from a mean of 58.8s (placebo), to 93.6s (25mg/kg diclofenac), 185.8s (50mg/kg diclofenac) and 231.7s (75mg/kg diclofenac). RCS scores decreased from a mean score of 5.6 (placebo), to 3.75 (25mg/kg diclofenac), 2.8 (50mg/kg diclofenac) and 1.75 (75mg/kg diclofenac). MDA levels reduced from 14.2ng/gr (placebo) to 9.6ng/gr (25mg/kg diclofenac), 8.4ng/gr (50mg/kg diclofenac) and 5.1ng/gr (75mg/kg diclofenac). Likely, TNF-α levels decreased from 67.9ng/gr (placebo) to 48.1ng/gr (25mg/kg diclofenac), 33.5ng/gr (50mg/kg diclofenac) and 21.3ng/gr (75mg/kg diclofenac). SOD levels, however, enhanced from 0.048U/mg (placebo) to 0.055U/mg (25mg/kg diclofenac), 0.14U/mg (50mg/kg diclofenac), and 0.18U/mg (75mg/kg diclofenac). Diclofenac sodium (25, 50, and 75mg/kg i.p.) effectively lowered the spike percentages and RCS scores linked with PTZ-induced epilepsy in rats, as well as significantly decreased MDA, TNF-α, IL-1β, PGE2 and increased SOD levels. Probably as a result of its anti-oxidative and anti-inflammatory effects, diclofenac sodium dramatically lowered seizure activity at both doses compared to placebo control. Each of these results were significant, with p-values of < 0.01, < 0.05. Therefore, the therapeutic application diclofenac sodium as a potential anticonvulsant should be investigated further.