title: Nitrate (NO3(-)) and nitrite (NO2(-)) are endocrine disruptors to downregulate expression of tyrosine hydroxylase and motor behavior through conversion to nitric oxide in early development of zebrafish.
abstract: With a view to consider the increasing concern over nitrogen pollution in the aquatic environment, we investigated effects of nitrate (NO3(-)) and nitrite (NO2(-)) on the activity of dopaminergic neuron in zebrafish embryos and larvae. Both nitrate and nitrite exposure decreased the expression of tyrosine hydroxylase (TH) in dopaminergic neurons at 48hpf. Only nitrite decreased the response to tactile stimulation at 72hpf, whereas both nitrate and nitrite decreased the swimming activity at 6dpf. When the embryos were exposed to nitrate or nitrite together with an estrogen receptor blocker (ICI 182,780), the decreases in TH expression and motor behavior caused by nitrate or nitrite alone were reversed suggesting the effects of nitrate and nitrite were mediated through estrogen receptor (ER). The result of co-incubation with an oxidoreductase inhibitor, diphenyleneiodonium, indicated the conversion to nitric oxide (NO) is likely to be responsible for the effects of nitrate and nitrite, which was further supported by the increased staining for NO after exposure. The present study demonstrates that nitrate and nitrite are neurotoxicants acting as an endocrine disruptor possibly through conversion to NO to downregulate the activity of dopaminergic neuron in early development of zebrafish.
authors.affiliation: Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto 860-8555, Japan.
authors.forename: Meshkatul
authors.initials: M
authors.lastname: Jannat
authors.affiliation: Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto 860-8555, Japan.
authors.forename: Ratu
authors.initials: R
authors.lastname: Fatimah
authors.affiliation: Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto 860-8555, Japan. Electronic address: mkishida@gpo.kumamoto-u.ac.jp.
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Kishida
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000201:enzymology; D004625:Embryo, Nonmammalian; D052244:Endocrine Disruptors / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D065171:Estrogen Receptor Antagonists / Q000494:pharmacology; D000077267:Fulvestrant; D015870:Gene Expression / Q000187:drug effects; D007814:Larva / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009566:Nitrates / Q000633:toxicity*; D009569:Nitric Oxide / Q000633:toxicity*; D009573:Nitrites / Q000633:toxicity*; D009861:Onium Compounds / Q000494:pharmacology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000378:metabolism
chemical_list: D052244:Endocrine Disruptors; D004791:Enzyme Inhibitors; D065171:Estrogen Receptor Antagonists; D009566:Nitrates; D009573:Nitrites; D009861:Onium Compounds; D011960:Receptors, Estrogen; D014874:Water Pollutants, Chemical; D000077267:Fulvestrant; D009569:Nitric Oxide; D004958:Estradiol; C007517:diphenyleneiodonium; D010088:Oxidoreductases; D014446:Tyrosine 3-Monooxygenase
keywords: Dopaminergic neuron; Early development; Nitrate; Nitric oxide; Nitrite; Zebrafish