title: Protective effects of caffeic acid against hypothalamic neuropeptides alterations induced by malathion in rat.
abstract: Exposure to pesticides is suspected to cause human health problems. Our study aimed to evaluate preventive effects of caffeic acid (3,4-dihydroxycinnamic acid) in the hypothalamus against malathion-induced neuropeptides gene expression alterations. Malathion at 100 mg/kg was administered intragastrically to rats alone or in combination with caffeic acid at 100 mg/kg during 4 weeks. A molecular expression of hypothalamic neuropeptides and plasmatic cholinesterase activity was investigated. Furthermore, we used in silico analysis, known as computational docking, to highlight the nature of acetylcholinesterase-malathion/caffeic acid interactions. Our findings showed differences in the responses and indicate that caffeic acid reversed malathion-induced decrease in corticotropin-releasing hormone mRNA but not brain-derived neurotrophic factor which presented an increased tendency. We suggest that caffeic acid can interact with acetylcholinesterase as the primary target of organophosphorus compounds. Results predict that caffeic acid can block partly the acetylcholinesterase gorge entrance via π-π stacking interaction with Tyr 124 and Trp 286 residues of the peripheral site leading to its stricture. Under this condition, we suggested that acetylcholine trafficking toward the catalytic site is ameliorated compared to malaoxon according to their sizes.
authors.affiliation: Laboratoire de Physiologie des Agressions, Département de Biologie, Faculté des Sciences de Tunis, Université El Manar, Tunis, Tunisie.
authors.forename: Raja
authors.initials: R
authors.lastname: Rezg
authors.forename: Bessem
authors.initials: B
authors.lastname: Mornagui
authors.forename: Jana Sopkova-de Oliveira
authors.initials: JS
authors.lastname: Santos
authors.forename: Fabienne
authors.initials: F
authors.lastname: Dulin
authors.forename: Saloua
authors.initials: S
authors.lastname: El-Fazaa
authors.forename: Noomen
authors.initials: N
authors.lastname: Ben El-Haj
authors.forename: Ronan
authors.initials: R
authors.lastname: Bureau
authors.forename: Najoua
authors.initials: N
authors.lastname: Gharbi
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology*; D007306:Insecticides / Q000378:metabolism / Q000633:toxicity*; D008294:Malathion / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D009479:Neuropeptides / Q000378:metabolism*; D051381:Rats
chemical_list: D000975:Antioxidants; D002109:Caffeic Acids; D007306:Insecticides; D009479:Neuropeptides; C100082:malaoxon; D000110:Acetylcholinesterase; C040048:caffeic acid; D008294:Malathion