Weak estrogenic activity of lindane in rats

Raizada, R. B.; Misra, P. K.; Saxena, Indra Gaurav; Datta, Kasturi; Dikshith, T. S. S.

doi:10.1080/15287398009529867

Cited by 30 publications

(12 citation statements)

References 13 publications

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“…Here, the former two showed similar strong antiestrogenicity with an EC 50 of 4.71 Â 10 À 7 and 4.03 Â 10 À 7 mol/L, respectively, which is consistent with the report that they had similar treatment efficacies in breast cancer (Howell et al, 2004). HCH performed as a weak ER antagonist in the recombinant yeast (EC 50 ¼4.60 Â 10 À 5 mol/L), although both its estrogenic and antiestrogenic activities have been observed in other organisms (Briz et al, 2011;Chadwick et al, 1988;Huang et al, 2006;Raizada et al, 1980). Because the binding of an antiestrogen to ER cannot initiate the expression of the reporter gene lac-Z, the inhibition effect test had to be executed by simultaneously exposing the yeast cells to E2 and the tested antagonist.…”

Section: Discussionsupporting

confidence: 79%

Combined action of estrogen receptor agonists and antagonists in two-hybrid recombinant yeast in vitro

Yang

Rao

et al. 2015

Ecotoxicology and Environmental Safety

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a b s t r a c tEstrogen receptor (ER) antagonistic chemicals in aquatic environments are believed to influence the binding of both endogenous and exogenous estrogens to ERs in aquatic organisms. Although the combined effects of estrogenic compounds have attracted much scientific concern, little work has been done on the influence of such antiestrogens on the biological effects of estrogens. This study focused on how the presence of different amounts of antagonists affects the results of ER agonist activity tests. To achieve this, three questions were stated and answered in sequence. A two-hybrid recombinant yeast assay mediated by ER was adopted, providing a single mode of action and single target of action for this study. Mixtures created by an ER agonist and three antagonists following the fixed-ratio principle were assessed. The concentration of 17β-estradiol causing maximum induction was set as the fixed dose of estrogen in the antagonist activity test (question 1). When the two classes of chemicals coexisted, antiestrogens, which as a whole behaved according to the concentration addition model (question 2), decreased the response of estrogen and compressed the concentration-response curves along the y-axis in the agonist activity test (question 3). This may cause the estradiol equivalent to be underestimated and potentially mask the action of estrogenic effects in toxicity evaluation of environmental samples.

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Section: Discussionsupporting

confidence: 79%

Combined action of estrogen receptor agonists and antagonists in two-hybrid recombinant yeast in vitro

Yang

Rao

et al. 2015

Ecotoxicology and Environmental Safety

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“…The results of administering lindane over two generations did not reveal any obvious changes in the extra endpoints for endocrine disrupting activity in any generation even at doses that manifest severe toxicity, including death, despite reports of estrogenic (Raizada et al, 1980) or antiestrogenic (Uphouse and Williams, 1989;Chadwick et al, 1988;Cooper et al, 1989) effects. In uterotrophic and Hershberger assays of lindane conducted in projects of the Ministry of the Environment, no estrogenic or antiestrogenic effects were detected; nor were any androgenic or antiandrogenic effects observed (data not shown).…”

Section: Assessment Of the Test Methodsmentioning

confidence: 99%

“…It has been reported as having estrogenic (Raizada et al, 1980) or antiestrogenic activity (U phous e and Williams , 1989;Chadwick et al, 1988;Cooper et al, 1989). Testicular damage, reduced sperm counts (Dalsenter et al, 1996), prolongation of the estrous cycle, and delayed vaginal opening (Uphouse and Williams, 1989;Chadwick et al, 1988;Cooper et al, 1989) have also been reported in rats.…”

Section: Introductionmentioning

confidence: 94%

Evaluation of a Two-Generation Reproduction Toxicity Study Adding Endopoints to Detect Endocrine Disrupting Activity Using Lindane

et al. 2005

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-A two-generation reproduction toxicity study in rats adding extra endpoints to detect endocrine disrupting activity was conducted using lindane by dietary administration at 0, 10, 60, and 300 ppm, for investigation of its utility. The extra endpoints included anogenital distance (AGD), nipple development, sexual maturation (vaginal opening and preputial separation), estrous cycle, spermatogenesis, sex organ weights, and blood hormone concentrations (thyroid and sex hormones). F1 offspring were examined for emotionality (open field test), motor coordination (rotarod test), as well as learning and memory (pole-climbing test). Hepatic drug-metabolizing enzyme activities were also measured. The results revealed general toxicological effects on parental animals, influence on reproductive function, and altered development of offspring; however, they did not demonstrate any distinct changes in the extra endpoints for detection of endocrine disrupting activity. Adult toxicity was observed in both F0 and F1 animals, including suppressed body weight gain and reduced food consumption in both sexes, and deaths of females at 300 ppm. Convulsions and irritability were observed during the perinatal period in pregnant F1 females given 300 ppm. Pathological examination revealed increased liver weights and centrilobular hepatocellular hypertrophy in both sexes and generations at 10 or 60 ppm and above; in addition, increased kidney weights and increased hyaline droplets in the proximal tubule epithelium, and basophilic renal tubules in males were noted at 10 ppm and above. Pituitary weights were decreased in F0 females and in F1 males and females and adrenal weights were increased in F1 males and females at 300 ppm; however, no histological changes were observed, and manifestations suggesting endocrine disrupting activity related to these changes were lacking. Hypertrophy of the thyroid follicular epithelium in F0 females at 300 ppm and in F1 males at 60 and 300 ppm, and decreases in T3 and/or T4 in both sexes and generations at 300 ppm were presumed to be secondary changes associated with the induction of hepatic drug-metabolizing enzymes. Blood hormone analysis revealed no changes in sex hormones attributable to lindane in males or females. Hepatic drug-metabolizing enzyme activities were increased dose-dependently from 10 ppm in both sexes and generations, with the rise in BROD activity being the most prominent. There were also increases in MROD, EROD, T-6β-OH, and T4-UDP-GT activities (BROD >> EROD > MROD, T-6β-OH, T4-UDP-GT). This suggests that while lindane most strongly induces CYP2B, it also upregulates a number of other drug metabolizing enzymes, such as CYP1A, CYP3A, and UDP-GT. As for effects on reproductive function, lack of maternal behavior, including lactation and retrieval behavior, and consequent total litter loss were observed in F1 dams at 300 ppm. There were no effects of lindane on the estrous cycle, spermatogenesis, mating, fertility, pregnancy, or parturition. Neonatal toxicity was observed in bot...

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“…0 1988 mers and metabolites have received most attention (2). Another organochlorine insecticide, y-hexachlorocyclohexane, also has adverse reproductive effects in both birds (7) and mammals (&9) and has been reported to have estrogenic activity (10). One well-recognized physiological effect of estrogenic activity in the rat is a reduction of food intake and body weight gain (11-13).…”

Section: Introductionmentioning

confidence: 98%

Possible antiestrogenic activity of lindane in female rats

Chang

et al. 1988

J. Biochem. Toxicol.

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During chronic peroral (PO) treatment of weanling, female Fischer 344 rats with daily injections (0.069 mmol/kg) of either 1,1'-(2,2,2-trichloroethylidene) bis [4-chlorobenzene] (p,p'-DDT), 2,4-dichlorophenoxy acetic acid (2,4-D), or gamma-hexachlorocyclohexane (lindane), the lindane treatment induced a significant 20% increase in body weight after 110 days. Further investigation with 0, 5, 10, 20, and 40 mg/kg lindane confirmed a significant increase in average body weight gain at the two highest doses after ten weeks of treatment. Significantly greater food consumption was observed, and the Lee index indicated that lindane treatment induced obesity. In addition to obesity, lindane caused a delay in vaginal opening, disrupted estrous cycling, reduced pituitary and uterine weight, and elevated food consumption during proestrus (when appetite is normally suppressed by estradiol). These responses suggest that, by inducing alterations in the reproductive function of the female rat and by interfering with hormonal regulation of energy balance, lindane may be antiestrogenic rather than estrogenic as previously proposed.

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Weak estrogenic activity of lindane in rats

Cited by 30 publications

References 13 publications

Combined action of estrogen receptor agonists and antagonists in two-hybrid recombinant yeast in vitro

Combined action of estrogen receptor agonists and antagonists in two-hybrid recombinant yeast in vitro

Evaluation of a Two-Generation Reproduction Toxicity Study Adding Endopoints to Detect Endocrine Disrupting Activity Using Lindane

Possible antiestrogenic activity of lindane in female rats

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