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Abstract
Theophylline, a methylxanthine used in the treatment of bronchial
asthma and chronic obstructive pulmonary diseases, has a narrow therapeutic index and a high propensity to induce toxicity.
The therapeutic use of theophylline is associated with a significant incidence of intractable seizures and mortality. However, the seizurogenic effect of the drug could not be satisfactorily explained by mechanisms like adenosine antagonism and phosphodiestrase inhibition.
Free radicals play a crucial role in health and disease. Also they have been implicated in many drug and chemical induced toxicities and thus the involvement of free radicals during theophylline seizures was explored.
The xanthine-xanthine oxidase system is an important pathway of generation of reactive oxygen species (ROS) in biological systems, and one of the major metabolites of theophylline is a substrate for xanthine oxidase. It is,thus, possible that the increased production of ROS during metabolism of high doses of theophylline could result in oxidant/antioxidant imbalance and thus precipitate neurotoxicity.
The aim of this study was to investigate the effect of some antioxidants like nimodipine, melatonin, propolis and selenium on theophylline-induced seizures in mice.
The studied animals were assigned to control and test groups as follows:Group 1: Normal control group, mice were injected with saline i.p.
Group 2: Mice were injected with theophylline in a single dose of 300 mg/kg i.p.
Group 3: Mice were injected with nimodipine in a single dose of 14mg/kg i.p 30 minutes before theophylline injection.
Group 4: Mice were injected with melatonin in a single dose of 80 mg /kg i.p 15 minutes before theophylline injection.
Group 5: Mice were given propolis in a single dose of 210 mg/kg orally before theophylline injection.
Group 6: Mice were given selenium in a single dose of 10 mg/kg orally before theophylline injection.
The mice were put into individual cages, and then had been observed for 60 minutes, and the following parameters had been studied:A- Percent animals having clonic/tonic convulsions.
B- Latency of onset of convulsions (min).
C- Percent mortality at one hour observation.
Biochemical studies:
After observing the percent incidence of convulsions and mortality for one hour, the animals were be decapitated under ether anesthesia. The brains were quickly removed for determination of malondialdehyde (MDA) and nitric oxide metabolites levels in the brain homogenates.