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Changes 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.

ABSTRACT: BACKGROUND:Atrazine 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. METHODS:The 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. RESULTS:No 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. CONCLUSION:The 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. © 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc.

SUBMITTER: Breckenridge CB

PROVIDER: S-EPMC5884089 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Changes 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.

Breckenridge Charles B CB Foradori Chad D CD Sawhney Coder Pragati P Simpkins James W JW Sielken Robert L RL Handa Robert J RJ

Birth defects research 20171114 3

<h4>Background</h4>Atrazine 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.<h4>Methods</h4>The 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 atrazin ...[more]

PMID: 29134775

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Project description:BackgroundEpidural fibrosis is one of the aetiologies of pain following a spinal revision surgery. It is reported that the specific members of the mitogen - activated protein kinases (MAPK) family might mediate neuropathic pain. However, roles of epidural fibrosis caused by repeated spinal surgeries and pain-related proteins in causing the post spinal surgery syndrome remain unknown. Using a rat spinal surgery epidural fibrosis and adhesion model, in this study, we evaluated and investigated the relationship between pain markers and epidural fibrosis.MethodsSprague-Dawley rats that underwent the spinal surgery were divided into three groups: group A (single laminectomy), group B (two repeated surgeries) and group C (three repeated surgeries). Dural thickness was measured in each experimental group, and immunohistochemical analysis and western blotting of mitogen-activated protein kinases were performed (ERK, p38 and JNK) using the spine cord.ResultsDural thickness was 6.363 ± 1.911??m in group A, 13.238 ± 2.123??m in group B and 19.4 ± 2.115??m in group C, respectively. In the western blotting, phosphorylated ERK expression gradually increased with the number of repeated surgeries, and expression in groups B (1.77-fold) and C (2.42-fold) increased as compared to expression in group A. Phosphorylated p38 showed an increasing trend with the number of repeated surgeries, and groups B (1.17-fold) and C (1.33-fold) expression increased compared with group A. However, phosphorylated JNK expression did not gradually increase with the number of repeated surgeries, and groups B (1.62-fold) and C (1.43-fold) expression increased compared with group A. Excluding phosphorylated JNK, immunohistochemical analysis revealed that phosphorylated ERK and p38 expression gradually increased with the number of repeated surgeries in the spine dorsal horn, as evidenced by western blotting.ConclusionsRepeated spinal surgeries may increase dural thickness and expression of phosphorylated ERK and p38 in the spinal dorsal horn, and it suggests that the neuropathic pain is likely induced by epidural fibrosis and that the pain increases with the number of repeated surgeries.

Dataset Information

Changes 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.

Publications

Changes 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.

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