ABSTRACT
Neurosteroids and micronutrient are known to possess neuromodulator and neuroprotective activities. The present study was designed to investigate the effect of 4'-chlorodiazepam (4CD) or ascorbic acid (Vit C) on phosphamidon (PM) induced modulation of cognitive function and oxidative stress in male Wistar rats. Cognitive function was measured by using step-down latency (SDL) on a continuous avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was estimated by measuring brain malondialdehyde (MDA) level, protein carbonyl (PC) and reduced glutathione (GSH) activity. A significant reduction in both acquisition and retention in SDL was found for the PM treated group at weeks 6 and 8 as compared to the control (p<0.001). PM caused a significant prolongation in both acquisition and retention in TL at 6 and 8 weeks as compared to the control (p<0.001). Two-week treatment of 4CD or Vit C antagonized the effect of PM on SDL and TL at 8th week. PM produced a statistically significant increase in the brain MDA and PC levels (p<0.001) and a significant decrease in the brain GSH activity (p<0.001). Treatment with 4CD or Vit C attenuated the effect of PM on MDA, PC and GSH activities. Results of this study suggest that Vit C and 4CD have potential in reversing cognitive dysfunction and oxidative stress induced by toxicants like PM in the brain.
Subject(s)
Ascorbic Acid/pharmacology , Benzodiazepinones/pharmacology , Cognition/drug effects , Insecticides/pharmacology , Oxidative Stress/drug effects , Phosphamidon/pharmacology , Animals , Antioxidants/pharmacology , Avoidance Learning/drug effects , Brain/drug effects , Brain/metabolism , Carrier Proteins/metabolism , Drug Interactions , Insecticides/antagonists & inhibitors , Male , Maze Learning/drug effects , Phosphamidon/antagonists & inhibitors , Rats , Rats, Wistar , Receptors, GABA-A/metabolismABSTRACT
The acute toxicity of fonofos and phosphamidon on three age classes of Artemia salina was evaluated. An increase in toxicity of these organophosphorous (OP) insecticides was found following longer development of A. salina. The effects of pretreatment with the nonselective muscarinic antagonist atropine, the two reversible acetylcholinesterease inhibitors physostigmine and pyridostigmine, and the cholinesterase-reactivating oxime 2-pyridine aldoxime methoiodide (2-PAM), as individual and combined pretreatments, on OP-induced lethality in 24 h Artemia were also investigated. The lethal action of both OP insecticides was prevented by pretreatment of 24 h Artemia with atropine and 2-PAM, while physostigmine proved ineffective against intoxication with both OP insecticides and pyridostigmine exhibited a low synergic effect. In both cases, the inhibitory effects of combinations of atropine (10(-5)M) plus 2-PAM were greater than those elicited by either drug alone, with the maximum protection afforded being 100%. Combined pretreatment of atropine (10(-5)M) plus physostigmine practically abolished the lethal effects induced by both insecticides. Pretreatment with 2-PAM (10(-6)M) plus physostigmine afforded maximal protection of 100% and 76% on the lethality induced by fonofos and phosphamidon, respectively. The data obtained suggest that the combination of atropine plus 2-PAM or physostigmine and the combined pretreatment of 2-PAM plus physostigmine are effective in the prevention of the lethal effects induced by fonofos and phosphamidon in A. salina larvae.
Subject(s)
Artemia/drug effects , Cholinesterase Inhibitors/toxicity , Fonofos/toxicity , Insecticides/toxicity , Phosphamidon/toxicity , Age Factors , Animals , Atropine/pharmacology , Carbamates/pharmacology , Cholinesterase Inhibitors/pharmacology , Cholinesterase Reactivators/pharmacology , Fonofos/antagonists & inhibitors , Insecticides/antagonists & inhibitors , Larva/drug effects , Muscarinic Antagonists/pharmacology , Phosphamidon/antagonists & inhibitors , Pralidoxime Compounds/pharmacology , Toxicity TestsABSTRACT
Vitamin C, when administered concurrently with a pesticide (endosulfan, phosphamidon or mancozeb), could significantly decrease the frequency of pesticide-induced clastogenic and mitosis-disruptive changes in the bone marrow cells of young Swiss albino mice. Of the three doses (10, 20 or 40 mg/kg b.wt./day) of the vitamin, the one which is double the human therapeutic dose (20 mg/kg b.wt./day) was most effective as an antimutagen to be followed by 40 mg and 10 mg. None of these doses of vitamin C showed any genotoxicity of their own for the parameters studied here.
Subject(s)
Antimutagenic Agents/pharmacology , Ascorbic Acid/administration & dosage , Chromosome Aberrations , Mutagenesis/drug effects , Animals , Bone Marrow Cells , Endosulfan/antagonists & inhibitors , Maneb/antagonists & inhibitors , Mice , Mice, Inbred Strains , Mitosis/drug effects , Phosphamidon/antagonists & inhibitors , Zineb/antagonists & inhibitorsABSTRACT
Phosphamidon intoxication (2 mg/kg body wt./day for 7 days) inhibited SOD activity, but enhanced the lipid peroxidation in various CNS regions. Administration of cithiolone (8 mg/kg body wt./day, ip for 7 days), however, elevated SOD activity and depleted lipid peroxidation. Interestingly, no significant change was observed either in SOD activity or in lipid peroxidation following simultaneous administration of phosphamidon and cithiolone.
