title: The role of multifunctional drug therapy as an antidote to combat experimental subacute neurotoxicity induced by organophosphate pesticides.
abstract: Organophosphate pesticides are used in agriculture where they are associated with numerous cases of intentional and accidental misuse. These toxicants are potent inhibitors of cholinesterases leading to a massive build-up of acetylcholine which induces an array of deleterious effects, including convulsions, oxidative damage and neurobehavioral deficits. Antidotal therapies with atropine and oxime yield a remarkable survival rate, but fail to prevent neuronal damage and behavioral problems. It has been indicated that multifunction drug therapy with potassium channel openers, calcium channel antagonists and antioxidants (either single-agent therapy or combination therapy) may have the potential to prevent cell death and/or slow down the processes of secondary neuronal damage. The aim of the present study, therefore, was to make a relative assessment of the potential effects of nicorandil (2 mg/kg), clinidipine (10 mg/kg), and grape seed proanthocyanidin (GSPE) extract (200 mg/kg) individually against subacute chlorpyrifos induced toxicity. The test drugs were administered to Wistar rats 2 h after exposure to Chlorpyrifos (CPF). Different behavioral studies and biochemical estimation has been carried in the study. The results showed that chronic administration of CPF significantly impaired learning and memory, along with motor coordination, and produced a marked increase in oxidative stress along with significantly reduced acetylcholine esterase (AChE) activity. Treatment with nicorandil, clinidipine and GSPE was shown to significantly improve memory performance, attenuate oxidative damage and enhance AChE activity in rats. The present study also suggests that a combination of nicorandil, clinidipine, and GSPE has a better neuroprotective effect against subacute CPF induced neurotoxicity than if applied individually. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1017-1026, 2016.
authors: Department of Pharmacology, Indo Soviet Friendship (ISF) College of Pharmacy, Moga, 142001, Punjab, India.
authors: Satinderpal
authors: S
authors: Singh
authors: Department of Pharmacology, Indo Soviet Friendship (ISF) College of Pharmacy, Moga, 142001, Punjab, India.|Faculty of Pharmacy, Campus Puncak Alam, Universiti Teknologi MARA (UiTM), 42300, Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.|Brain Degeneration and Therapeutics Group, Brain and Neuroscience Communities of Research, Universiti Teknologi MARA (UiTM), 40450, Shah Alam, Selangor Darul Ehsan, Malaysia.
authors: Atish
authors: A
authors: Prakash
authors: Department of Pharmacology, Indo Soviet Friendship (ISF) College of Pharmacy, Moga, 142001, Punjab, India.
authors: Shamsherjit
authors: S
authors: Kaur
authors: Faculty of Pharmacy, Campus Puncak Alam, Universiti Teknologi MARA (UiTM), 42300, Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.|Brain Degeneration and Therapeutics Group, Brain and Neuroscience Communities of Research, Universiti Teknologi MARA (UiTM), 40450, Shah Alam, Selangor Darul Ehsan, Malaysia.
authors: Long Chiau
authors: LC
authors: Ming
authors: Faculty of Pharmacy, Campus Puncak Alam, Universiti Teknologi MARA (UiTM), 42300, Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.|Brain Degeneration and Therapeutics Group, Brain and Neuroscience Communities of Research, Universiti Teknologi MARA (UiTM), 40450, Shah Alam, Selangor Darul Ehsan, Malaysia.
authors: Vasudevan
authors: V
authors: Mani
authors: Faculty of Pharmacy, Campus Puncak Alam, Universiti Teknologi MARA (UiTM), 42300, Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.|Brain Degeneration and Therapeutics Group, Brain and Neuroscience Communities of Research, Universiti Teknologi MARA (UiTM), 40450, Shah Alam, Selangor Darul Ehsan, Malaysia.
authors: Abu Bakar Abdul
authors: AB
authors: Majeed
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D004390:Chlorpyrifos / Q000633:toxicity*; D004095:Dihydropyridines / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D056604:Grape Seed Extract / Q000494:pharmacology*; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D018782:Maze Learning; D008568:Memory / Q000187:drug effects; D053580:Muscle Strength / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020108:Nicorandil / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D044945:Proanthocyanidins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000931:Antidotes; D004095:Dihydropyridines; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D007306:Insecticides; D018696:Neuroprotective Agents; D044945:Proanthocyanidins; D020108:Nicorandil; C065927:cilnidipine; D000110:Acetylcholinesterase; D004390:Chlorpyrifos
keywords: GSPE; acetylcholinesterase; chlorpyrifos; clinidipine; nicorandil; oxidative stress