title: Differential cholinesterase inhibition in the rat brain regions by dichlorvos and protective effect of Decalepis hamiltonii roots.
abstract: Dichlorvos (DDVP) causes neurotoxicity primarily by inhibiting cholinesterase (ChE) which is the characteristic feature of organophosphate pesticides. In this study, we found for the first time that DDVP shows differential inhibition of ChE (acetylcholinesterase+butyrylcholinesterase) in various rat brain regions. A single dose of DDVP (1/3 LD(50)) after 16 h of treatment elicited ChE inhibition in the brain regions which was highest in striatum and lowest in cerebellum. The inhibition of ChE by DDVP has been shown to be accompanied with induction of oxidative stress. Further, we investigated the protective potential of the aqueous extract of the roots of Decalepis hamiltonii (DHA), having potent antioxidant constituents, against DDVP-induced ChE inhibition in various rat brain regions. Pretreatment of rats with multiple doses of DHA, 50 and 100mg/kg b.w., for 7 consecutive days did not produce any significant change in ChE activity. Pretreatment of rats with DHA, at high dose, significantly protected against DDVP-induced ChE inhibition in all the brain regions except cerebellum. Pretreatment of rats with DHA, at low dose, showed significant protection in striatum, cortex, and pons against DDVP-induced ChE inhibition. The protective activity of DHA can be attributed to the characterized potent antioxidant constituents which could have an important role in preventing ChE inhibition by inducing the DDVP detoxifying enzymes. We strongly believe that these antioxidant constituents are prospective novel nutriceuticals.
authors.affiliation: Department of Microbiology, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. anup@uab.edu
authors.forename: Anup
authors.initials: A
authors.lastname: Srivastava
authors.forename: T
authors.initials: T
authors.lastname: Shivanandappa
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D029062:Apocynaceae / Q000737:chemistry; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004006:Dichlorvos / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D058851:GPI-Linked Proteins; D018696:Neuroprotective Agents; D010936:Plant Extracts; D004006:Dichlorvos; D000110:Acetylcholinesterase; C548246:Ache protein, rat; D002091:Butyrylcholinesterase