title: Urinary amino acid alterations in 3-year-old children with neurodevelopmental effects due to perinatal dioxin exposure in Vietnam: a nested case-control study for neurobiomarker discovery.
abstract: In our previous study of 3-year-old children in a dioxin contamination hot spot in Vietnam, the high total dioxin toxic equivalent (TEQ-PCDDs/Fs)-exposed group during the perinatal period displayed lower Bayley III neurodevelopmental scores, whereas the high 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-exposed group displayed increased autistic traits. In autistic children, urinary amino acid profiles have revealed metabolic alterations in the amino acids that serve as neurotransmitters in the developing brain. Therefore, our present study aimed to investigate the use of alterations in urinary amino acid excretion as biomarkers of dioxin exposure-induced neurodevelopmental deficits in highly exposed 3-year-old children in Vietnam. A nested case-control study of urinary analyses was performed for 26 children who were selected from 111 3-year-old children whose perinatal dioxin exposure levels and neurodevelopmental status were examined in follow-up surveys conducted in a dioxin contaminated hot spot. We compared urinary amino acid levels between the following 4 groups: (1) a high TEQ-PCDDs/Fs and high TCDD-exposed group; (2) a high TEQ-PCDDs/Fs but low TCDD-exposed group; (3) a low TEQ-PCDDs/Fs exposed and poorly developed group; and (4) a low TEQ-PCDDs/Fs exposed and well-developed group. Urinary levels of histidine and tryptophan were significantly decreased in the high TEQ-PCDDs/Fs and high TCDD group, as well as in the high TEQ-PCDDs/Fs but low TCDD group, compared with the low TEQ-PCDDs/Fs and well-developed group. However, the ratio of histidine to glycine was significantly lower only in the high TEQ-PCDDs/Fs and high TCDD group. Furthermore, urinary histidine levels and the ratio of histidine to glycine were significantly correlated with neurodevelopmental scores, particularly for language and fine motor skills. These results indicate that urinary histidine is specifically associated with dioxin exposure-induced neurodevelopmental deficits, suggesting that urinary histidine may be a useful marker of dioxin-induced neurodevelopmental deficits and that histaminergic neurotransmission may be an important pathological contributor to dioxin-mediated neurotoxicity.
authors.affiliation: Department of Public Health, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Muneko
authors.initials: M
authors.lastname: Nishijo
authors.affiliation: Biomedical and Pharmaceutical Research Center, Vietnam Military Medical University, Ha Noi, Vietnam.
authors.forename: Pham The
authors.initials: PT
authors.lastname: Tai
authors.affiliation: Department of Public Health, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Nguyen Thi Nguyet
authors.initials: NT
authors.lastname: Anh
authors.affiliation: Department of Public Health, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Tran Ngoc
authors.initials: TN
authors.lastname: Nghi
authors.affiliation: Department of Public Health, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakagawa
authors.affiliation: Biomedical and Pharmaceutical Research Center, Vietnam Military Medical University, Ha Noi, Vietnam.
authors.forename: Hoang
authors.initials: H
authors.lastname: Van Luong
authors.affiliation: Biomedical and Pharmaceutical Research Center, Vietnam Military Medical University, Ha Noi, Vietnam.
authors.forename: Tran Hai
authors.initials: TH
authors.lastname: Anh
authors.affiliation: School of Nursing, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Morikawa
authors.affiliation: Department of Obstetrics and Gynecology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Waseda
authors.affiliation: Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, 920-0942, Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Kido
authors.affiliation: System Emotional Science, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Nishijo
mesh_terms: D000596:Amino Acids / Q000652:urine*; D015415:Biomarkers / Q000652:urine*; D016022:Case-Control Studies; D002675:Child, Preschool; D004147:Dioxins / Q000633:toxicity*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D065886:Neurodevelopmental Disorders / Q000139:chemically induced* / Q000378:metabolism / Q000652:urine*; D011247:Pregnancy; D014744:Vietnam
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D004147:Dioxins