scholarly journals Comparison of In Vitro Endocrine Activity of Phthalates and Alternative Plasticizers

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Hélène Moche ◽  
Aouatif Chentouf ◽  
Sergio Neves ◽  
Jean-Marc Corpart ◽  
Fabrice Nesslany

Because of the deleterious effects of phthalates, regulations have been taken to decrease their use, and the needs for alternatives are increasing. Due to the concerns about the endocrine-disrupting properties of phthalates, it was deemed necessary to particularly investigate these effects for potential substitutes. In this study, we compared the in vitro endocrine activity of several already used potential alternative plasticizers (DEHT, DINCH, and TOTM) or new substitutes (POLYSORB® isosorbide and POLYSORB® ID 46) to one of 2 phthalates, DEHP and DINP. Effects of these chemicals on 3 common mechanisms of endocrine disruption, i.e., interaction with estrogen receptors (ER), androgen receptors (AR), or steroidogenesis, were studied using extensively used in vitro methods. In the E-Screen assay, only DEHP moderately induced MCF-7 cell proliferation; none of the other tested substances were estrogenic or antiestrogenic. No androgenic or antiandrogenic activity in MDA-kb2 cells was shown for any of the tested phthalates or alternatives. On the other hand, both DEHP and DINP, as well as DEHT, DINCH, and TOTM, disrupted steroidogenesis in the H295R assay, mainly by inducing an increase in estradiol synthesis; no such effect was observed for POLYSORB® isosorbide and POLYSORB® ID 46.

2020 ◽  
Vol 49 (2) ◽  
pp. 135-143
Author(s):  
C.H. Li ◽  
M.Y. Du ◽  
K.T. Wang

This study was conducted to assess the effects of 2,4-epibrassionolide (EBR) on mold decay caused by Rhizopus stolonifer and its capability to activate biochemical defense reactions in postharvest peaches. The treatment of EBR at 5 μM possessed the optimum effectiveness on inhibiting the Rhizopus rot in peach fruit among all treatments. The EBR treatment significantly up-regulated the expression levels of a set of defense-related enzymes and PR genes that included PpCHI, PpGns1, PpPAL, PpNPR1, PpPR1 and PpPR4 as well as led to an enhancement for biosynthesis of phenolics and lignins in peaches during the incubation at 20 °C. Interestingly, the EBR-treated peaches exhibited more striking expressions of PR genes and accumulation of antifungal compounds upon inoculation with the pathogen, indicating a priming defense could be activated by EBR. On the other hand, 5 μM EBR exhibited direct toxicity on fungal proliferation of R. stolonifer in vitro. Thus, we concluded that 5 μM EBR inhibited the Rhizopus rot in peach fruit probably by a direct inhibitory effect on pathogen growth and an indirect induction of a priming resistance. These findings provided a potential alternative for control of fungal infection in peaches during the postharvest storage.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11505-e11505
Author(s):  
A. Del Giglio ◽  
J. F. Pinto ◽  
F. A. Fonseca ◽  
S. R. Marsicano ◽  
P. O. Delgado ◽  
...  

e11505 Background: We have previously shown that alkylating agent based chemotherapy regimens (AQT) could induce MIS in the PBMNF of BC patients in parallel to a decrease in the expression of the protein hMSH2 in these cells (Fonseca et al., 2005, Breast Cancer Res, 7, R28–32). Since plasma DNA derives mainly from tumor cells, we wanted to know if chemotherapy would also produce MIS in tumor DNA and if this phenomenon could be reproduced in vitro. Methods: 33 previously untreated female BC patients with a mean age of 51 years received AQT(16 ACT;3FAC;2 TAC;1FEC;10AC). Samples from 3 additional patients who received Fulvestrant only as neoadjuvant therapy were also included. Blood (pfDNA and PBMNNF) and urine (ufDNA) were evaluated at time 0,3 and 6 months with 6 MIS markers (BAT40,BAT26, MR2,TP53 PCR15.1, APC and ALU). Levels of fpDNA and fuDNA were measured by spectrophotometry. We incubated in vitro cultures of MCF- 7 cells and PBMNF cells with M at a dose of 0.7μg/ml for 30 minutes with and without A at 20% of the M dose and evaluated serially for 48 hours for MIS and hMH2 expression by immunohistochemistry. Results: We observed at least one MIS event in the PBMNF, fpDNA or fuDNA in 87%, 80% and 80% of the patients, respectively, mainly in BAT40 and BAT 26 markers. There was only 14.74% of concordance of MIS alterations between PBMNF and fpDNA and 8. 42% between fpDNA and fuDNA. Patients receiving Hormones also exhibited MIS. Interestingly, fpDNA levels increased significantly in patients with measurable disease who responded to therapy (47.4 ± 13.34 vs 14.37± 5.32; p = 0.021). In vitro, incubating MCF-7 cells and normal PBMNF cells with M ±A, we observed that we could induce MIS in both MCF-7 cells and normal PBMNF cells but A prevented MIS only in normal PBMNF cells. In normal PBMNF cells without A that sustained MIS there was a significantly decreased percentage of cells expressing hMSH2 ( 96% vs 57% p < 0.001). Conclusions: We conclude that Chemotherapy as well as Fulvestran can induce MIS in normal and malignant cells and that in vitro these effects could be reproduced by treatment with M and prevented in normal cells by A. No significant financial relationships to disclose.


Author(s):  
Tae Maeshima ◽  
Ryosuke Iijima ◽  
Machiko Watanabe ◽  
Satoru Yui ◽  
Fumio Itagaki

Abstract Background Since antipsychotics induce hyperprolactinemia via the dopamine D2 receptor, long-term administration may be a risk factor for developing breast tumors, including breast cancer. On the other hand, some antipsychotic drugs have been reported to suppress the growth of breast cancer cells in vitro. Thus, it is not clear whether the use of antipsychotics actually increases the risk of developing or exacerbating breast tumors. The purpose of this study was to clarify the effects of antipsychotic drugs on the onset and progression of breast tumors by analyzing an adverse event spontaneous reporting database and evaluating the proliferation ability of breast cancer cells. Methods Japanese Adverse Drug Event Report database (JADER) reports from April 2004 to April 2019 were obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) website. Reports of females only were analyzed. Adverse events included in the analysis were hyperprolactinemia and 60 breast tumor-related preferred terms. The reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC) were used to detect signals. Furthermore, MCF-7 cells were treated with haloperidol, risperidone, paliperidone, sulpiride, olanzapine and blonanserin, and cell proliferation was evaluated by WST-8 assay. Results In the JADER analysis, the IC signals of hyperprolactinemia were detected with sulpiride (IC, 3.73; 95% CI: 1.81–5.65), risperidone (IC, 3.69; 95% CI: 1.71–5.61), and paliperidone (IC, 4.54; 95% CI: 2.96–6.12). However, the IC signal of breast tumors was not observed with any antipsychotics. In cell-based experiments, MCF-7 cells were treated with six antipsychotics at concentrations of 2 and 32 μM, and none of the drugs showed any growth-promoting effects on MCF-7 cells. On the other hand, blonanserin markedly suppressed the growth of MCF-7 cells at a concentration of 32 μM, and the effect was concentration dependent. Conclusions Analysis of the JADER using the IC did not show breast tumor signals due to antipsychotic drugs. In in vitro experiments, antipsychotics did not promote MCF-7 cell proliferation whereas blonanserin suppressed MCF-7 cell growth. Further research on the effects of blonanserin on the onset and progression of breast tumor is expected.


2021 ◽  
Vol 12 (3) ◽  
pp. 3332-3347

As essential oils (EOs) represent a new source of efficient and safe agents for health nowadays, the present review brings together the in vitro methods widely used to evaluate the antioxidant and some biological activities especially, antidiabetic, anticancer, antimicrobial, and anti-inflammatory activities of EOs, in order to valorize these EOs and to highlight their potential benefits. Moreover, each method cited is along with its aim, principle, advantages and limitations, experimental protocols, and notes. Hence, this review will help researchers working on EOs, to save time while accessing this summary document on the one hand, and on the other hand, it will contribute to scientific approval of in vitro antioxidant and biological effects of EOs for future useful purposes.


2000 ◽  
pp. 419-425 ◽  
Author(s):  
F Broglio ◽  
A Benso ◽  
C Gottero ◽  
G Muccioli ◽  
R Deghenghi ◽  
...  

OBJECTIVE: Peptidyl and non-peptidyl synthetic GH secretagogues (GHS) possess significant GH-, prolactin (PRL)- and ACTH/cortisol-releasing activity after i.v. and even p.o. administration, acting via specific hypothalamo-pituitary receptors in both animals and humans. The hexapeptide hexarelin (HEX) is a paradigmatic GHS whose activities have been widely studied in humans. The heptapeptide Ala-His-d-2-methyl-Trp-Ala-Trp-d-Phe-Lys-NH(2) (alexamorelin, ALEX) is a new synthetic molecule which inhibits GHS binding in vitro, but its endocrine activity has never been studied in humans. DESIGN: In six young adults we studied the effects of 1.0 and 2.0 microgram/kg i.v. ALEX or HEX on GH, PRL, ACTH, cortisol and aldosterone levels and those of 20mg p.o. ( approximately 300 microgram/kg) on GH levels. RESULTS: Basal GH, PRL, ACTH, cortisol and aldosterone levels in all testing sessions were similar. ALEX and HEX (1.0 and 2.0 microgram/kg i.v.) induced the same dose-dependent increase of GH and PRL levels. Both ALEX and HEX induced a dose-dependent increase of ACTH and cortisol levels. The ACTH and cortisol responses to the highest ALEX dose were significantly higher than those after HEX. Aldosterone levels significantly increased after both i.v. ALEX doses, but not after HEX. The GH response to 20mg p.o. ALEX was higher, though not significantly, than that to the same HEX dose. CONCLUSION: ALEX, a new GHS, shows the same GH-releasing activity as HEX. On the other hand, ALEX seems endowed with an ACTH-releasing activity more marked than that of HEX; this evidence could explain the significant increase of aldosterone levels after its i.v. administration.


Author(s):  
Atefeh Nasri ◽  
Raimo Pohjanvirta

AbstractPhytoestrogens have been widely praised for their health-promoting effects, whereas synthetic environmental estrogens are considered a toxicological risk to human health. The aim of this study was therefore to compare in vitro the estrogenic, cytotoxic, and genotoxic profiles of three common estrogen-like endocrine-disrupting chemicals: the phytoestrogens 8-prenylnaringenine (8-PN) and genistein and the synthetic xenoestrogen tartrazine. As assessed by a yeast bioreporter assay and estrogen-dependent proliferative response in human mammary gland adenocarcinoma cell line (MCF-7), 8-PN showed the highest estrogen-like activity of the three compounds, followed by tartrazine and genistein. After 24-h incubation on MCF-7 cells, all three compounds exhibited low cytotoxicity in the lactate dehydrogenase assay and no genotoxicity in the micronucleus assay. These results demonstrate that 8-PN, genistein and tartrazine possess variable estrogenic activity but display little cellular toxicity in short-term tests in vitro. No difference between phytoestrogens and a synthetic xenoestrogen could be established.


2005 ◽  
Vol 48 (2) ◽  
pp. 81-86 ◽  
Author(s):  
Kamil Kuča ◽  
Jiří Cabal ◽  
Jiří Kassa ◽  
Daniel Jun ◽  
Martina Hrabinová

1. The efficacy of the oxime HLö-7 and currently used oximes (pralidoxime, obidoxime, HI-6) to reactivate acetylcholinesterase inhibited by various nerve agents (sarin, tabun, cyclosarin, VX) was tested by in vitro methods. 2. Both H oximes (HLö-7, HI-6) were found to be more efficacious reactivators of sarin and VX-inhibited acetylcholinesterase than pralidoxime and obidoxime. On the other hand, their potency to reactivate tabun-inhibited acetylcholinesterase is very low and does not reach the reactivating efficacy of obidoxime. In the case of cyclosarin, the oxime HI-6 was only found to be able to sufficiently reactivate cyclosarin-inhibited acetylcholinesterase in vitro. 3. Thus, the oxime HLö-7 does not seem to be more efficacious reactivator of nerve agent-inhibited acetylcholinesterase than HI-6 according to in vitro evaluation of their reactivation potency and, therefore, it is not more suitable to be introduced for antidotal treatment of nerve agent-exposed people than HI-6.


2007 ◽  
Vol 2 (12) ◽  
pp. 1934578X0700201 ◽  
Author(s):  
Brenda S. Wright ◽  
Anita Bansal ◽  
Debra M. Moriarity ◽  
Sayaka Takaku ◽  
William N. Setzer

The leaf essential oils of Beilschmiedia sp. nov. “chancho blanco”, Cinnamomum costaricanum, Ocotea meziana, Ocotea sp. nov. “los llanos” and Ocotea sp. nov. “small leaf” showed notable in-vitro cytotoxic activity on MCF-7 cells. In order to examine possible synergistic effects of essential oil components, cytotoxic activities of 1:1 binary mixtures of a number of volatile compounds were determined. Notable synergistic cytotoxic enhancement was observed for mixtures of various compounds with citral, citronellal, and artemisia ketone. The cytotoxic activity of α-humulene, on the other hand, was antagonized by pinenes, thujene, and camphene. Likewise, camphene and terpinen-4-ol reduced the activity of β-caryophyllene.


Planta Medica ◽  
2011 ◽  
Vol 77 (12) ◽  
Author(s):  
D Sevim ◽  
FS Senol ◽  
I Orhan ◽  
B Şener ◽  
E Kaya

Planta Medica ◽  
2015 ◽  
Vol 81 (16) ◽  
Author(s):  
OML Bayazeid ◽  
F Yalcin ◽  
M İlhan ◽  
H Karahan ◽  
E Kupeli-Akkol ◽  
...  
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