Abstract
Problem statement: The Cyclooxygenases (COXs), the key enzymes that convert arachidonic acid to Prostaglandins (PGs), had been implicated in physiological and pathophysiological functions in the CNS. Non-Stesoidal Anti-Inflammatory Drugs (NSAIDs), COX inhibitors, were used largely to treat febrile condition, pain state and for prevention of and therapeutics of many diseases. However the role of PGs and NSAIDs in the seizure activity has been disputed. The aim of this study was to evaluation the effect of intraperitoneally injection of different doses of Phenylbutazone on PTZ-induced seizure threshold in mice. Approach: Mice were divided into 9 groups randomly: The first group received saline normal (ip) (control group); the second group received Carboxy Methyl Cellulose (CMC) 0.5% (ip) (vehicle group) and the next groups received respectively different doses of Phenylbutazone (5, 10, 20, 40, 60, 80 and 100 mg kg-1 ip) 45 min before determination of seizure threshold induced by PTZ. Results: Results showed that PTZ-induced seizure threshold in control mice was 34.75±1.54 mg kg-1. Intraperitoneal injection of Phenylbutazone showed significant (p<0.05) increase of PTZ-induced seizure threshold in a dose dependently manner compared with control group. Conclusion: Phenylbutazone has anticonvulsant effects on mice. Nevertheless, new studies must be carried out in order to determine the beneficial effects of NSAIDs in treatment of epilepsy.
Highlights
The Cyclooxygenases (COX) are the principle and involved
It has been reported that the pretreatment of COX-2 inhibitors including celecoxib aggravated kainic acidinduced seizure activity in rodents and aggravated kainic acid-induced neuronal death in the hippocampus (Baik et al, 1999)
The broad COX inhibitor such as ibuprofen caused deficits in spatial learning in a water maze (Shaw et al, 2003), whereas several reports showed the post-treatment of COX-2 inhibitors restored the memory deficit and learning behaviors and prevented seizure-induced neuronal death (Gobbo and O'Mara, 2004; Kunz and Oliw, 2001a; 2001b)
Summary
Processes have been implicated in both acute and chronic neurodegenerative conditions such as epilepsy. The key enzymes that convert arachidonic acid to prostaglandins (including PGE2, PGD2, PGF2α, PGI2 and thromboxane A2), have been implicated in physiological and pathophysiological functions in the CNS, the cellular mechanisms by which COX reaction products are involved have yet to be elucidated (Chen and Bazan, 2005) These enzymes have shown to be expressed in different areas of brain besides peripheral organs and speculated to play an important role in neurological disorders (Dhir et al, 2008). COX-1 plays a previously unrecognized part in the neuroinflammation, a key stage in the development of several neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, traumatic brain injury, HIV-associated dementia, ischemic stroke and epilepsy, whereas COX-2, mainly localized in pyramidal neurons, is expected to predominantly contribute to increase PG synthesis in response to insults that directly challenge neurons, such as ischemia and exitotoxicity Under these circumstances, COX-2 inhibition seems to afford protection without altering the inflammatory responce.
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