title: The role of multifunctional drug therapy against carbamate induced neuronal toxicity during acute and chronic phase in rats.
abstract: The current study has been designed to examine the effect of multifunctional drug therapy on carbofuran induced acute (2.187 mg/kg, s.c.) and sub-acute (0.2187 mg/kg, s.c.) neurotoxicity in male wistar rats. Drug treatment which includes nimodipine (Ca(2+) channel blocker), diazepam, ropinirole (dopamine agonist) and GSPE (antioxidant) was started 2h after carbofuran administration. Morris water maze was employed for aiming spatial memory. Narrow beam walk and rotarod were employed for testing motor functions. Brain acetylcholinesterase activity, thiobarbituric acid reactive species, nitrite, reduced glutathione, catalase levels, and mitochondrial complexes were also estimated. Carbofuran treatment resulted in significant development of cognitive and motor functions manifested as impairment in learning and memory along with increased thiobarbituric acid reactive species, nitrite levels and decreased acetylcholinesterase activity, reduced glutathione, catalase levels, and mitochondrial complexes. The standard antidote therapy (atropine) was not able to provide neuroprotection but was able to provide symptomatic relief. The multifunctional drug therapy attenuated carbofuran induced cognitive and motor dysfunction, acetylcholinesterase activity and other biochemical parameters. The triple combination in sub-acute study may be avoided in future as two drug combinations provide adequate neuroprotection. Thus it can be concluded that standard antidotal therapy may not provide neuroprotection while the multifunctional drug therapy offers neuroprotection against carbofuran and may dramatically increase survival and life quality.
authors.affiliation: Department of Pharmacology, I.S.F. College of Pharmacy, Moga, Punjab, India.
authors.forename: Karan Singh
authors.initials: KS
authors.lastname: Chahal
authors.affiliation: Department of Pharmacology, I.S.F. College of Pharmacy, Moga, 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. Electronic address: atishprakash@gmail.com.
authors.forename: Atish
authors.initials: A
authors.lastname: Prakash
authors.affiliation: 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.forename: Abu Bakar Abdul
authors.initials: AB
authors.lastname: Majeed
mesh_terms: D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000166:cytology / Q000187:drug effects; D002235:Carbofuran / Q000633:toxicity*; D004359:Drug Therapy, Combination; D008297:Male; D018782:Maze Learning; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D045442:Rotarod Performance Test
chemical_list: D000931:Antidotes; D002235:Carbofuran
keywords: Carbofuran; Mitochondrial dysfunction; Multifunctional drug therapy; Neurotoxicity; Oxidative stress