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dc.contributor.authorBreckenridge, Charles B.*
dc.contributor.authorForadori, Chad D.*
dc.contributor.authorSawhney Coder, Pragati*
dc.contributor.authorSimpkins, James W.*
dc.contributor.authorSielken, Robert L.*
dc.contributor.authorHanda, Robert J.*
dc.date.accessioned2018-04-02T18:41:41Z
dc.date.available2018-04-02T18:41:41Z
dc.date.issued2018-02-15
dc.identifier.citationChanges in Sensitivity to the Effects of Atrazine on the Luteinizing Hormone Surge in Female Sprague-Dawley Rats after Repeated Daily Doses: Correlation with Liver Enzyme Expression 2018, 110 (3):246 Birth Defects Researchen
dc.identifier.issn24721727
dc.identifier.pmid29134775
dc.identifier.doi10.1002/bdr2.1130
dc.identifier.urihttp://hdl.handle.net/10150/627193
dc.description.abstractBackgroundAtrazine suppression of the LH surge slowly develops over time and peaks after 4 days; sensitivity to atrazine decreases after 8 or 14 days of dosing. Adaptation of the LH response was correlated with increased phase I and phase II liver enzyme activity/expression. MethodsThe effect of atrazine on the LH surge was evaluated in female Sprague-Dawley rats administered 100 mg/kg/day atrazine by gavage for 1, 2, 3, or 4 consecutive days or 6.5, 50, or 100 mg/kg/day atrazine for 4, 8, or 14 days. ResultsNo statistically significant effects of atrazine were seen on peak plasma LH or LH area under the curve (AUC) after one, two, or three doses of 100 mg/kg/day. Four daily doses of 50 or 100 mg/kg atrazine significantly reduced peak LH and LH AUCs, whereas 6.5 mg/kg/day had no effect. After 8 or 14 days of treatment, statistically significantly reduced peak LH and LH AUC were observed in the 100 mg/kg/day dose group, but not in the 6.5 or 50 mg/kg/day dose groups, although significantly reduced LH was observed in one sample 9 hr after lights-on in the 50 mg/kg/day dose group on day 14. The number of days of treatment required to achieve a significant suppression of the LH surge is consistent with the repeat-dose pharmacokinetics of the chlorotriazines. ConclusionThe apparent adaptation to the effect of atrazine on the LH surge after 8 or 14 days may be related to the induction of phase I or, more likely, phase II metabolism observed in this study after 8 days, or to a decreased sensitivity of the hypothalamic-pituitary-adrenal axis or an homeostatic adaption of the effect of atrazine on the LH surge mechanism. Birth Defects Research 110:246-258, 2018. (c) 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc.
dc.description.sponsorshipSyngenta Crop Protection, LLC; Syngentaen
dc.language.isoenen
dc.publisherWILEYen
dc.relation.urlhttp://doi.wiley.com/10.1002/bdr2.1130en
dc.rights© 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License.en
dc.subjectLH surgeen
dc.subjectgavageen
dc.subjectatrazineen
dc.subjectsensitivityen
dc.subjectadaptationen
dc.subjectphase I metabolismen
dc.subjectphase II metabolismen
dc.titleChanges in Sensitivity to the Effects of Atrazine on the Luteinizing Hormone Surge in Female Sprague-Dawley Rats after Repeated Daily Doses: Correlation with Liver Enzyme Expressionen
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Dept Basic Med Sci, Coll Meden
dc.identifier.journalBirth Defects Researchen
dc.description.noteOpen access article.en
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
dc.contributor.institutionSyngenta Crop Protection LLC; Greensboro North Carolina
dc.contributor.institutionDepartment of Basic Medical Sciences; University of Arizona College of Medicine; Phoenix Arizona
dc.contributor.institutionWIL Research; Ashland Ohio
dc.contributor.institutionPhysiology and Pharmacology; West Virginia University; Morgantown West Virginia
dc.contributor.institutionSielken & Associates Consulting, Inc.; College Station Texas
dc.contributor.institutionDepartment of Basic Medical Sciences; University of Arizona College of Medicine; Phoenix Arizona
refterms.dateFOA2018-09-12T07:11:13Z
html.description.abstractBackgroundAtrazine suppression of the LH surge slowly develops over time and peaks after 4 days; sensitivity to atrazine decreases after 8 or 14 days of dosing. Adaptation of the LH response was correlated with increased phase I and phase II liver enzyme activity/expression. MethodsThe effect of atrazine on the LH surge was evaluated in female Sprague-Dawley rats administered 100 mg/kg/day atrazine by gavage for 1, 2, 3, or 4 consecutive days or 6.5, 50, or 100 mg/kg/day atrazine for 4, 8, or 14 days. ResultsNo statistically significant effects of atrazine were seen on peak plasma LH or LH area under the curve (AUC) after one, two, or three doses of 100 mg/kg/day. Four daily doses of 50 or 100 mg/kg atrazine significantly reduced peak LH and LH AUCs, whereas 6.5 mg/kg/day had no effect. After 8 or 14 days of treatment, statistically significantly reduced peak LH and LH AUC were observed in the 100 mg/kg/day dose group, but not in the 6.5 or 50 mg/kg/day dose groups, although significantly reduced LH was observed in one sample 9 hr after lights-on in the 50 mg/kg/day dose group on day 14. The number of days of treatment required to achieve a significant suppression of the LH surge is consistent with the repeat-dose pharmacokinetics of the chlorotriazines. ConclusionThe apparent adaptation to the effect of atrazine on the LH surge after 8 or 14 days may be related to the induction of phase I or, more likely, phase II metabolism observed in this study after 8 days, or to a decreased sensitivity of the hypothalamic-pituitary-adrenal axis or an homeostatic adaption of the effect of atrazine on the LH surge mechanism. Birth Defects Research 110:246-258, 2018. (c) 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc.


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