Sex-dependent aromatase activity in rat offspring after pre- and postnatal exposure to triphenyltin chloride

Hobler, Carolin; Andrade, Andrey José de; Grande, Simone Wichert; Gericke, Christine; Talsness, Chris E.; Appel, Klaus E.; Chahoud, Ibrahim; Grote, Konstanze

doi:10.1016/j.tox.2010.08.003

Cited by 22 publications

(12 citation statements)

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“…Its endocrine activity has often been ascribed to inhibition of aromatase although the exact mechanism has not been fully elucidated (for details, see Grote et al, 2006;Hobler et al, 2010). Based on the skeletal examination, we confirmed the NOAEL of 3 ppm for reproductive toxicity previously reported, corresponding to a mean daily intake of about 0.28 -0.35 mg kg À 1 bw (Grote et al, 2006).…”

Section: Thoraxsupporting

confidence: 86%

Examination of Japanese Quail Chicks in One-Generation Feeding Studies for Effects of the Agrochemicals Dimethoate, Fentin Hydroxide, and Vinclozolin on Skeletal Development

Niemann

Grote

Stoll

et al. 2012

Avian Biology Research

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An established method for evaluation of skeletal anomalies was successfully adapted to Japanese quail (Coturnix coturnix japonica) and performed on 793 untreated 1-day old chicks to develop an historical control database. Incomplete ossification of the pelvic bones and irregular position of the toes were rather frequently observed. Subsequently, 702 chicks from the treatment groups in three one-generation reproduction studies with the pesticides dimethoate, triphenyltin (fentin) hydroxide, and vinclozolin were compared to their respective controls and the whole historical database. Presumed treatment-related effects were confined to a higher number of chicks with incomplete ossification of vertebrae and pelvis when the hens had been administered fentin hydroxide at a dietary level of 30 ppm for up to 6 weeks, corresponding to a mean daily substance intake of 3.1 -3.9 mg kg À 1 body weight (bw). Thus, inclusion of teratological findings as a further endpoint confirmed the previously established NOAEL of 3 ppm (equal to 0.28 -0.35 mg kg À 1 bwyday) based on reproductive effects in this study. No effects on skeletal development were seen with dimethoate and vinclozolin up to the highest dietary concentrations of 70 and 500 ppm, corresponding to estimated mean daily intakes of about 8 or 56 mg kg À 1 bw. The suitability of the method for reliable detection of skeletal anomalies was proven. The established method can be considered useful in providing additional information for ecotoxicological risk assessment.

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Section: Thoraxsupporting

confidence: 86%

Examination of Japanese Quail Chicks in One-Generation Feeding Studies for Effects of the Agrochemicals Dimethoate, Fentin Hydroxide, and Vinclozolin on Skeletal Development

Niemann

Grote

Stoll

et al. 2012

Avian Biology Research

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“…Ovarian aromatase activity was unaffected at both time points investigated. In contrast, testicular aromatase activity was increased in males on PND 21 and decreased at adulthood independent from the duration of treatment (Hobler et al, 2010). Tributyltin induced an increase in the mRNA content of P450(17a) and P450arom in rat hippocampal slices.…”

Section: Organotins Affect Aromatase Activity and Levelsmentioning

confidence: 87%

Triorganotin compounds - ligands for “rexinoid” inducible transcription factors: Biological effects

Brtko

Dvořák

2015

Toxicology Letters

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“…The formation of tritiated water is proportional to the amount of estrogen produced during aromatization. Brain tissues were homogenized and afterwards subjected to the 3H 2 O release assay as previously described (Grote et al, 2006;Hobler et al, 2010). Briefly, dissected brain samples were homogenized in TEKS buffer (Tris HCl 50 mM, Na 2 EDTA 2H20 1 mM, KCl 100 mM pH 7.4) containing 0.1% (w/v) Na 2 S 2 O 5 .…”

Section: Aromatase Activity Analysismentioning

confidence: 99%

Amitraz changes NE, DA and 5-HT biosynthesis and metabolism mediated by alterations in estradiol content in CNS of male rats

et al. 2017

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(2017). Amitraz changes NE, DA and 5-HT biosynthesis and metabolism mediated by alterations in estradiol content in CNS of male rats. Chemosphere, 181 518-529. Amitraz is a formamidine insecticide/acaricide that alters different neurotransmitters levels, among other neurotoxic effects. Oral amitraz exposure (20, 50 and 80 mg/kg bw, 5 days) has been reported to increase serotonin (5-HT), norepinephrine (NE) and dopamine (DA) content and to decrease their metabolites and turnover rates in the male rat brain, particularly in the striatum, prefrontal cortex, and hippocampus. However, the mechanisms by which these alterations are produced are not completely understood. One possibility is that amitraz monoamine oxidase (MAO) inhibition could mediate these effects. Alternatively, it alters serum concentrations of sex steroids that regulate the enzymes responsible for these neurotransmitters synthesis and metabolism. Thus, alterations in sex steroids in the brain could also mediate the observed effects. To test these hypothesis regarding possible mechanisms, we treated male rats with 20, 50 and 80 mg/kg bw for 5 days and then isolated tissue from striatum, prefrontal cortex, and hippocampus. We then measured tissue levels of expression and/or activity of MAO, catechol-O-metyltransferase (COMT), dopamine-b-hydroxylase (DBH), tyrosine hydroxylase (TH) and tryptophan hydroxylase (TRH) as well as estradiol levels in these regions. Our results show that amitraz did notAbbreviations: AD, aldehyde dehydrogenase; AMZ, amitraz; ARO, aromatase; AAADC, aromatic amino acid decarboxylase; CNS, central nervous system; COMT, catechol-O-metyltransferase; Ct, cycle threshold; DA, dopamine; DBH, dopamine-bhydroxylase; DOPA, 3,4-dihydroxyphenylalanine; DOPAC, 3,4-hydroxyphenylacetic acid; DHT, dihydrotestosterone; E2, 17b-estradiol; FC, prefrontal cortex; HC, hippocampus; HPLC, high performance liquid chromatography; HVA, homovanillic acid; 5-HT, serotonin; 5-HTP, 5-hydroxytryptophan; 5-HIAA, 5-hydroxy-3-indolacetic acid; LD 50 , Lethal Dose 50; LOQ, Quantification limit; MAO, monoamine oxidase; MHPG, 3-metoxy-4-hydroxyphenylethyleneglycol; NE, norepinephrine; NSD-1015, m-hydroxymethylhydrazine; SD, standard deviation; ST, striatum; T, testosterone; TH, tyrosine hydroxylase; TMX, tamoxifen; TRH, tryptophan hydroxylase.* Chemosphere 181 (2017) 518e529 inhibit MAO activity at these doses, but altered MAO, COMT, DBH, TH and TRH gene expression, as well as TH and TRH activity and estradiol levels. The alteration of these enzymes was partially mediated by dysregulation of estradiol levels. Our present results provide new understanding of the mechanisms contributing to the harmful effects of amitraz.

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Sex-dependent aromatase activity in rat offspring after pre- and postnatal exposure to triphenyltin chloride

Cited by 22 publications

References 87 publications

Examination of Japanese Quail Chicks in One-Generation Feeding Studies for Effects of the Agrochemicals Dimethoate, Fentin Hydroxide, and Vinclozolin on Skeletal Development

Examination of Japanese Quail Chicks in One-Generation Feeding Studies for Effects of the Agrochemicals Dimethoate, Fentin Hydroxide, and Vinclozolin on Skeletal Development

Triorganotin compounds - ligands for “rexinoid” inducible transcription factors: Biological effects

Amitraz changes NE, DA and 5-HT biosynthesis and metabolism mediated by alterations in estradiol content in CNS of male rats

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