title: Inhibition of acetylcholinesterase by metabolites of copper pyrithione (CuPT) and its possible involvement in vertebral deformity of a CuPT-exposed marine teleostean fish.
abstract: In a previous study, we demonstrated that exposure to an antifouling biocide, copper pyrithione (CuPT), early during life induced vertebral deformity in the larvae of a marine fish, the mummichog (Fundulus heteroclitus). Skeletal deformities may be caused by inhibition by of acetylcholiensterase (AChE) activity, and to elucidate the mechanism underlying the CuPT-associated vertebral deformity, we first examined whether CuPT, zinc pyrithione (ZnPT), and their degradation products could inhibit AChE activity in the fish. Two of the degradation products, 2,2'-dipyridyldisulfide [(PS)(2)] and 2,2'-dithiobispyridine-N-oxide [(PT)(2)], but neither CuPT nor ZnPT, exhibited prominent AChE-inhibiting activity. Secondly, thin-layer chromatography revealed that mummichog hepatic microsomes metabolized CuPT to produce (PS)(2) in a microsome-dependent manner. The AChE inhibition induced in CuPT-exposed fish is likely due to (PS)(2) that was produced through metabolism of acquired CuPT. (PS)(2) may cause therefore skeletal deformity in CuPT-exposed fish by means of its neuromuscular blocking properties, through a mechanism similar to that proposed for animals exposed to organophosphorous pesticides.
authors.affiliation: National Research Institute of Fisheries and Environment of Inland Sea, Fisheries Research Agency, Hatsukaichi, Hiroshima 739-0452, Japan. kmochida@fra.affrc.go.jp
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Mochida
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Ito
authors.forename: Hiroya
authors.initials: H
authors.lastname: Harino
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Onduka
authors.forename: Akira
authors.initials: A
authors.lastname: Kakuno
authors.forename: Kazunori
authors.initials: K
authors.lastname: Fujii
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives / Q000494:pharmacology; D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000110:Acetylcholinesterase / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004220:Disulfides / Q000494:pharmacology; D005260:Female; D023781:Fundulidae / Q000002:abnormalities*; D007814:Larva / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009942:Organometallic Compounds / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity*; D011725:Pyridines / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity*
chemical_list: C541884:2,2'-dithiobispyridine-N-oxide; D002800:Cholinesterase Inhibitors; D004220:Disulfides; D009942:Organometallic Compounds; D011725:Pyridines; C487833:copper pyrithione; C001105:2,2'-dipyridyl disulfide; D015082:2,2'-Dipyridyl; D000110:Acetylcholinesterase; C010423:pyrithione zinc