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" Influence of antioxidants on some of the adverse effects and antiseizure activity of phenytoin in animal models "
/محمدرضا آقایی قزوینی
; Taghi Ghafghazi, Valiollah Haj Hashemi, Mohsen Ani
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Isfahan University of Medical Sciences
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Latin Dissertation
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| Language of Document
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English
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| Record Number
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102527
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| Doc. No
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T8483
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QV,85,A266i,2002
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Aghaye Ghazvini, Mohammad Reza
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| Title & Author
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Influence of antioxidants on some of the adverse effects and antiseizure activity of phenytoin in animal models/محمدرضا آقایی قزوینی
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| College
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Schools, Pharmacy
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| Date
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, 2002
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IX, 140 p.: tab, diag
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| Abstract
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BACRGROUND: Phenytoin induced oxidative stress has been proposed to be involved in the teratogenicity of this drug. In this study its role in antiseixure activity and somc other adverse effects of phenytoin has been investigated. METhIODS: Groups of male rats or mice were suh ccted to different schedules of longterm phenytoin treatment with or without one of the antioxidants a-tocopherol acetate, ascorbic acid or sodium sclenite supplementation. The body weight, serum tiobarhituric acid reactive material, alkaline phosphatase, arninotransferases and glucose levels, redblood cells indices, prothromhine time, response to myorelaxant effect of pancuroniurn or anesthesia of urethane and ketamine of treated animals were then investigated- Other groups of male rats were chronically treated with one of the above mentioned antioxidants for seven days and their susceptibility zo phenytoin antisei'rure activity were then assessed by maximal electroshock test. RESUL TS: Chronic treatment with the high dose o f phenvtoin, 240 mg kg'day_ but notits lower doses o160 or 120 rngfkg. resulted in: 1n increased serum thiobarbituric acid reactivity (P < 0.05)) 2 21 reduction in animal total body weight (p<O.0S) 3) reduction of serum alkaline phosphatase activity (P<0.05). 4) prulnnga~ion of loss of rig]itin.g-reflex latency following urethane administration (P <0.001) 5) h rpur spunsivness to pancuronium m arda arnt effect (P <01101) Pretreatment with antioxidant sigrncanrly reversed all these altcratiorns, except slowed weight an rate (P <0.05). Auiioxidan supp۰eIncntatian, on the other hand, did not alter phenvtnin anticanvulsant potency during maxirnat electroshock test. Paradoxically, simultaneous adrnimstration of ascorbic acid with phenytoin augmented phenytoin influence on urethane anesthetic activity (P <0.001). CONCLThese results indicate that plienytoin induced oxidative stress mayplay a crucial role in developit cnt of at least some of its adverse effects and therefore. antioxidant 5upplernentatian seems worthy to be furti~er investigated as adjuvant therapy to reduce phenwtoin toxicity..
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| Subject
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Phyenytoin
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Phenytoin.- Descriptor(s): Phenytoin- adverse effects
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Seizures
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Anticonvulsants
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Antioxodants
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Ascorbic acid
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Family, Name
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Ghafghazi, Taghi
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Haj Hashemi, Valiollah
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Ani, Mohsen
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| Translated Title Supplied by Cataloguer
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بررسی تاثیر آنتیاکسیدانها بر عوارض جانبی و فعالیت ضد تشنجی فنیتوئین در مدلهای حیوانی
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