title: Effect of phosphamidon on convulsive behavior and biochemical parameters: modulation by progesterone and 4'-chlorodiazepam in rats.
abstract: Phosphamidon (PHOS) has been shown to affect nervous system adversely. The present study was designed to explore the modulation of the effects of PHOS on convulsions by neurosteroids, progesterone (PROG), and 4'-chlorodiazepam (4'-CD), in both acute and chronic seizure models. In acute study, seizures were induced by either pentylenetetrazole (PTZ) injection or maximal electroshock seizures, while in the chronic study, kindling was induced by injecting PTZ (30 mg/kg, s.c.) on alternate days three times in a week. Oxidative stress was assessed in the brain by measuring the levels of malondialdehyde (MDA), acetylcholinesterase (AChE), and non-protein thiol (NP-SH). PROG and 4'-CD were able to modulate the PHOS-induced convulsions in acute PTZ convulsions as well as in chronic kindling model. However, they failed to reverse the derangements in oxidative stress parameters of MDA and NP-SH produced by PHOS in kindled animals. PROG significantly increased the AChE activity in untreated rats, while PROG and 4'-CD reversed the AChE activity inhibition induced by PHOS. The study indicates a possible anticonvulsive mechanism of neurosteroids, since both PROG and 4'-CD reversed PHOS-induced inhibition of AChE activity. The neurosteroids seem to play a protective role in PHOS-induced convulsions besides their antioxidant property.
authors.affiliation: Department of Pharmacology, University College of Medical Sciences, University of Delhi, Delhi, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Joshi
authors.forename: Tarun
authors.initials: T
authors.lastname: Arora
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Mehta
authors.forename: Amit K
authors.initials: AK
authors.lastname: Sharma
authors.forename: Naveen
authors.initials: N
authors.lastname: Rathor
authors.forename: Kapil D
authors.initials: KD
authors.lastname: Mehta
authors.forename: Prabha
authors.initials: P
authors.lastname: Mahajan
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Mediratta
authors.forename: Basu D
authors.initials: BD
authors.lastname: Banerjee
authors.forename: Krishna K
authors.initials: KK
authors.lastname: Sharma
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002908:Chronic Disease; D003975:Diazepam / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004597:Electroshock; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010433:Pentylenetetrazole; D010707:Phosphamidon / Q000633:toxicity*; D011374:Progesterone / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000378:metabolism* / Q000517:prevention & control / Q000523:psychology; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: C488690:4'-chlordiazepam; D000975:Antioxidants; D007306:Insecticides; D013438:Sulfhydryl Compounds; D010707:Phosphamidon; D011374:Progesterone; D008315:Malondialdehyde; D000110:Acetylcholinesterase; D003975:Diazepam; D010433:Pentylenetetrazole