SEARCH · PubMed Health

Results for “Benzhydryl Compounds”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources

PubMed2001

Mutagenic potential of bisphenol A diglycidyl ether (BADGE) and its hydrolysis-derived products in the Ames Salmonella assay.

The mutagenicity of bisphenol A diglycidyl ether (BADGE), its first and second hydrolysis products (the diol epoxide and bis-diol of BADGE, respectively) and the bis-chlorohydrin of BADGE were investigated using the Ames Salmonella assay with strains TA98, TA100, TA1535 and TA1537. The assays were performed in the absence and presence of various concentrations of rat liver S9 fraction. The results obtained confirm the mutagenic power of BADGE in strains TA100 and TA1535 and show a positive response to the diol epoxide of BADGE in these strains, although the latter compound was approximately 10 times less potent than the former. A lack of mutagenic activity of the bis-diol of BADGE and the chlorohydrin under study is also shown. These findings suggest that BADGE and, to a much lesser extent, the diol epoxide of BADGE may constitute a genotoxic hazard, but not the bis-diol or bis-chlorohydrin of BADGE.

Animals↗

PubMed2005

Synthetic LXR agonists increase LDL in CETP species.

Liver X receptor (LXR) nuclear receptors regulate the expression of genes involved in whole body cholesterol trafficking, including absorption, excretion, catabolism, and cellular efflux, and possess both anti-inflammatory and antidiabetic actions. Accordingly, LXR is considered an appealing drug target for multiple indications. Synthetic LXR agonists demonstrated inhibition of atherosclerosis progression in murine genetic models; however, these and other studies indicated that their major undesired side effect is an increase of plasma and hepatic triglycerides. A significant impediment to extrapolating results with LXR agonists from mouse to humans is the absence in mice of cholesteryl ester transfer protein, a known LXR target gene, and the upregulation in mice but not humans of cholesterol 7alpha-hydroxylase. To better predict the human response to LXR agonism, two synthetic LXR agonists were examined in hamsters and cynomolgus monkeys. In contrast to previously published results in mice, neither LXR agonist increased HDL-cholesterol in hamsters, and similar results were obtained in cynomolgus monkeys. Importantly, in both species, LXR agonists increased LDL-cholesterol, an unfavorable effect not apparent from earlier murine studies. These results reveal additional problems associated with current synthetic LXR agonists and emphasize the importance of profiling compounds in preclinical species with a more human-like LXR response and lipoprotein metabolism.

Animals↗

PubMed1977

The electrolytic conductivity detector as an element-selective gas chromatographic detector.

The response and elemental selectivity of the electrolytic conductivity detector (E1CD) to nitrogen-, chlorine-, and sulfur-containing compounds has been investigated as a function of chemical structure, furnace chemistry conditions (i.e., reaction gas, furnace temperature, catalyst, and post-furnace chemical abstractors), and solubilization-and-ionization processes (electrolytic chemistry and electrolytic conductance). The "profiling" of detector response for the gas-liquid chromatographic-E1CD analysis of selected compounds under defined furnace chemistry reaction conditions and electrolytic chemistry included the determination of detector signal to noise ratio, peak tailing, and elemental selectivity. Detector response and conductivity phenomena are discussed in terms of gas-phase furnace chemistry reactions, post-furnace reaction or abstraction processes, and solution-phase ionization and neutralization processes occurring in the conductivity cell.

Antidepressive Agents↗

PubMed1996

Effects of the calcium channel blockers Dotarizine and Flunarizine on cerebrovascular reactivity.

Dotarizine and Flunarizine are piperazine derivatives considered to be effective compounds for the treatment of various cerebrovascular disorders. In the present study the influence of these two drugs on changes in cerebral vessel diameter and blood flow velocity were measured and compared utilising transcranial Doppler sonography during hyperventilation in anaesthetized cats. Drugs were administered in 15 min intravenous infusions at a dose of 0.05 mg/kg/min. This investigation revealed that the 15 min intravenous administration of both compounds abolished the cerebral vasoconstrictor effects of hyperventilation and due to vasodilator effects they increased blood flow velocity to initial values. No statistically significant differences were found between the vasodilator effects of Dotarizine and Flunarizine. Results obtained suggest that Dotarizine, a novel piperazine derivative, has similar vasodilator and Ca2+ channel blocking effects on cerebrovascular reactivity compared to the widely clinically applied Flunarizine.

Animals↗

PubMed1996

Environmental estrogens: effects on cholesterol lowering and bone in the ovariectomized rat.

Representative non-steroidal estrogens, from common environmental sources such as plants, pesticides, surfactants, plastics, and animal health products, demonstrated an ability to lower serum cholesterol and prevent bone loss. Specifically, select environmental estrogens (coumestrol, genistein, methoxychlor, bisphenol A, and zeranol) effectively lowered total serum cholesterol in an estrogen-dependent animal model, the ovariectomized rat. Of these entities, coumestrol, methoxychlor, and zeranol prevented ovariectomy-induced bone loss. In an in vitro environment, these compounds competed with 17beta-estradiol for estrogen receptor binding and stimulated cell proliferation in a human breast cancer cell line (MCF-7). In addition to their well-documented effects on reproductive tissue, various environmental estrogens can dramatically affect non-reproductive parameters such as cholesterol lowering and bone metabolism.

Adenocarcinoma↗

PubMed2006

Endocrine regulation of HOX genes.

Hox genes have a well-characterized role in embryonic development, where they determine identity along the anteroposterior body axis. Hox genes are expressed not only during embryogenesis but also in the adult, where they are necessary for functional differentiation. Despite the known function of these genes as transcription factors, few regulatory mechanisms that drive Hox expression are known. Recently, several hormones and their cognate receptors have been shown to regulate Hox gene expression and thereby mediate development in the embryo as well as functional differentiation in the adult organism. Estradiol, progesterone, testosterone, retinoic acid, and vitamin D have been shown to regulate Hox gene expression. In the embryo, the endocrine system directs axial Hox gene expression; aberrant Hox gene expression due to exposure to endocrine disruptors contributes to the teratogenicity of these compounds. In the adult, endocrine regulation of Hox genes is necessary to enable such diverse functions as hematopoiesis and reproduction; endocrinopathies can result in dysregulated HOX gene expression affecting physiology. By regulating HOX genes, hormonal signals utilize a conserved mechanism that allows generation of structural and functional diversity in both developing and adult tissues. This review discusses endocrine Hox regulation and its impact on physiology and human pathology.

Animals↗

PubMed1999

Effects of dotarizine and flunarizine on chromaffin cell viability and cytosolic Ca2+.

Dotarizine (a novel piperazine derivative with antimigraine properties) and flunarizine (a Ca2+ channel antagonist) were compared concerning: first, their ability to cause chromaffin cell damage in vitro; second, the possible correlation of their octanol/water partition coefficients and those of another 28 compounds (i.e., Ca2+ channel antagonists, blockers of histamine H1 receptors, antimycotics, beta-adrenoceptor antagonists, neuroleptics), with their ability to cause cell damage; third, their capacity to protect the cells against the damaging effects of veratridine; and fourth, their capabilities to enhance the basal cytosolic Ca2+ concentration in fura-2-loaded single chromaffin cells, or to modify the pattern of [Ca2+]i oscillations elicited by veratridine. After 24-h exposure to 1-30 microM dotarizine, the viability of bovine adrenal chromaffin cells (measured under phase contrast or as lactate dehydrogenase, released into the medium) was similar to that of control, untreated cells; at 100 microM, 80% lactate dehydrogenase release was produced. At 1-3 microM flunarizine caused no cell damage; however 10 microM caused 20% lactate dehydrogenase release and 30 and 100 microM over 90% lactate dehydrogenase release. The time course of cell damage was considerably faster for flunarizine, in comparison to dotarizine. Out of 30 molecules tested (at 10 microM), having different octanol/water partition coefficients (log P), dotarizine was among the molecules causing no cell damage; flunarizine caused 20% cell loss, lidoflazine and verapamil over 50% cell loss, and penfluridol, draflazine, astemizole or nifedipine over 80% cell loss. No correlation was found between log P and cytotoxicity. Both dotarizine (10-30 microM) and flunarizine (3-10 microM) provided protection against veratridine-induced cell death; however, at 30 microM dotarizine afforded a pronounced protection while flunarizine enhanced the cytotoxic effects of veratridine. Dotarizine (30 microM) (but not flunarizine) caused a prompt transient elevation of the basal [Ca2+]i. Both compounds abolished the K+-induced increases of [Ca2+]i as well as the oscillations of [Ca2+]i induced by veratridine. The blocking effects of dotarizine were readily reversed after washout, while those of flunarizine were long-lasting. These differences might be relevant to the clinical use of dotarizine as an antimigraine drug.

Animals↗

PubMed2003

[Estrogenic activity of some environmental chemicals].

The study was designed to explore the estrogenic activity of environmental disrupters [n-4-noniphenol (NP), bisphenol A (bisA) and dibutylphthalate (DBP)]. Estrogen-respective breast cancer cell line T47D was grown in DMEM medium containing 10% bovine serum. Five days before the addition of the test compounds, the cell were washed in phosphate-buffered saline, and the medium was substituted with a phenol red-free DMEM medium containing 5% dextran charcoal-stripped FBS. The respective test compound was added in fresh medium and the control cell received only the vehicle (ethanol). The proliferation of T47D cells was analyzed by MTT assay, 3H-TdR incorporation assay and flow sytometer. The results indicated that, compared with the EtOH control cell, the test compounds (n-4-noniphenol, Bisphenol A and dibutylphthalate), like estradiol, markedly enhanced the proliferation of T47D cell and the metaphase of cell division, and the results showed time-dependent and dose-dependent model. These data showed that the tested chemicals could enhance the proliferation of human cervix cancer cell in vitro. This might hinted that these chemicals possessed estrogenic activity and they might play their estrogen through estrogenic receptor.

Benzhydryl Compounds↗

PubMed2004

Steroid activities comparison of natural and food wrap compounds in human breast cancer cell lines.

In this study, we tested and compared the endocrine disruption activities of compounds in materials used to package foods (bisphenol A, bisphenol F, and bisphenol A diglycidylether BADGE) with natural molecules (genistein, apigenin, kaempferol, and tangeretin) in the human breast cancer cell lines MCF-7 (ER(+)) and MDA-MB453 (AR(+); GR(+)). Octylphenol was also chosen as a xenoestrogen reference. Two compounds had no estrogenic activity: BADGE and tangeretin. Genistein was the most active compound in the E-Screen assay with MCF-7, followed by octylphenol, bisphenol F, bisphenol A and apigenin, with kaempferol the least potent. All estrogenic compounds competed with 17beta-estradiol for binding to the MCF-7 ER and their estrogenic effects were abolished in the presence of tamoxifen, an ER antagonist. In MDA-MB453 cells transfected with pMMTVneo-Luc, all compounds had anti-androgenic activities, with octylphenol the most potent. Kaempferol, genistein, and apigenin were more potent anti-androgens than bisphenols A or F. The natural compounds had a biphasic effect on luciferase activity. At high concentrations, genistein (10(-5)M) and apigenin (10(-6)M) acted as GR agonists in transfected MDA-MB453 cells. Furthermore, apigenin, at a concentration of 10(-5)M, may act as a partial androgen receptor (AR) agonist, as nilutamide, an AR antagonist, inhibited its activity by 26%.

Anticarcinogenic Agents↗

PubMed2005

Impact of induced fit on ligand binding to the androgen receptor: a multidimensional QSAR study to predict endocrine-disrupting effects of environmental chemicals.

We investigated the influence of induced fit of the androgen receptor binding pocket on free energies of ligand binding. On the basis of a novel alignment procedure using flexible docking, molecular dynamics simulations, and linear-interaction energy analysis, we simulated the binding of 119 molecules representing six compound classes. The superposition of the ligand molecules emerging from the combined protocol served as input for Raptor, a receptor-modeling tool based on multidimensional QSAR allowing for ligand-dependent induced fit. Throughout our study, protein flexibility was explicitly accounted for. The model converged at a cross-validated r(2) = 0.858 (88 training compounds) and yielded a predictive r(2) = 0.792 (26 test compounds), thereby predicting the binding affinity of all compounds close to their experimental value. We then challenged the model by testing five molecules not belonging to compound classes used to train the model: the IC(50) values were predicted within a factor of 4.5 compared to the experimental data. The demonstrated predictivity of the model suggests that our approach may well be beneficial for both drug discovery and the screening of environmental chemicals for endocrine-disrupting effects, a problem that has recently become a cause for concern among scientists, environmental advocates, and politicians alike.

Benzhydryl Compounds↗

PubMed2000

Benzylidene lactam compound, KNK437, a novel inhibitor of acquisition of thermotolerance and heat shock protein induction in human colon carcinoma cells.

Cells exposed to heat or other types of stressors transiently synthesize a group of proteins known as heat shock proteins (HSPs). A nonlethal heat treatment can elicit in the cells an ability to resist subsequent lethal heat treatments. We report here that a novel benzylidene lactam compound, KNK437, dose-dependently inhibited the acquisition of thermotolerance and the induction of various HSPs including HSP105, HSP70, and HSP40 in COLO 320DM (human colon carcinoma) cells. The induction of heat-inducible HSP70, which is reported to be involved in the development of thermotolerance, was inhibited at mRNA levels by treatment with KNK437. This compound also inhibited the acquisition of thermotolerance as developed by sodium arsenite. However, it did not increase thermosensitivity in nontolerant cells. The effect of KNK437 was much greater than that of quercetin, a bioflavonoid that was previously reported to inhibit the acquisition of thermotolerance as well as the induction of HSPs. We conclude that this drug is a novel inhibitor of the acquisition of thermotolerance caused by the induction of HSPs.

Arsenites↗

PubMed1989

Covalent binding of 4,4'-methylenebis-(2-chloroaniline) to rat liver DNA in vivo and of its N-hydroxylated derivative to DNA in vitro.

The binding of [ring-3H]4,4'-methylenebis(2-chloroaniline) (MOCA) to rat liver DNA following i.p. injection is demonstrated. Three discrete adducts were eluted on HPLC following enzymic hydrolysis to the nucleoside level. Three adducts, with the same retention times on HPLC, were present after i.p. injection of the N-acetyl derivative of MOCA tritiated in the benzene rings. Only two of these adducts were found when the N-acetyl derivative, tritiated on the acetyl group, was used. Thus, at least one of the adducts formed by MOCA is not acetylated. The N-hydroxy derivative of MOCA was synthesised and reacted with DNA in vitro. Following enzymic hydrolysis of this DNA, the major product was shown to co-elute with the radiolabelled non-acetylated adduct produced in the liver DNA of animals injected with [ring-3H]MOCA. This same compound was also isolated following the reaction of N-hydroxy-4-amino-3-chlorobenzyl alcohol with DNA, and subsequent enzymic hydrolysis. The NMR and mass spectra of the synthetic adduct were consistent with N-(deoxyadenosin-8-yl)-4-amino-3-chlorobenzyl alcohol. Thus, the major adduct formed in vivo has involved cleavage of the bond between the methylene bridge and one of the aromatic nuclei of MOCA.

Acetylation↗

PubMed2001

Estrogenic potency of benzophenone and its metabolites in juvenile female rats.

The estrogenic activity of benzophenone and its metabolites, benzhydrol and p-hydroxybenzophenone, were investigated in vitro by estrogen receptor (ER) competitive ligand binding assay and in vivo by uterotrophic assay in juvenile female Sprague-Dawley (SD) rats. p-Hydroxybenzophenone as well as diethylstilbestrol and bisphenol A, known xeno-estrogenic compounds, competed with fluorescein-labeled 17 beta-estradiol to bind human recombinant ER alpha in a concentration-dependent manner. Fifty percent inhibitory values (IC50) of diethylstilbestrol, bisphenol A, and p-hydroxybenzophenone were approximately 10(-8), 10(-5), and 5 x 10(-5) M, respectively. However, neither the parent compound nor benzhydrol at concentrations from 10(-9) to 5 x 10(-4) M impaired the binding of 17 beta-estradiol to ER alpha. Juvenile female rats (21-days-old) were given s.c. injections of benzophenone, its metabolites, and 17 beta-estradiol for 3 days. Administration of p-hydroxybenzophenone (100-400 mg/kg) elicited an increase in absolute and relative uterine weights in a dose-dependent manner and 17 beta-estradiol (10 micrograms/kg) increased uterine weight approximately fourfold relative to control. The uterine response caused by both compounds was accompanied by an increase in luminal epithelial height and stromal cells in the uterus and an increase in thickness of vaginal epithelial cell layers with cornification. In contrast, benzophenone and benzhydrol at a dose of 400 mg/kg affected neither uterine weight nor histological changes of the uterus and vagina. These results indicate that p-hydroxybenzophenone, a metabolite of benzophenone, exhibits intrinsic xeno-estrogenic activity in the female reproductive tract.

Animals↗

PubMed1978

Effects of 3-trifluoromethyl-alpha-ethylbenzhydrol (RGH-3332), a new enzyme inducer on the central nervous system of rats. Part II.

3-Trifluoromethyl-alpha-ethylbenzhydrol (RGH-3332, Zixoryn) had been reported to induce the hepatic mixed function oxydase system similarly to phenobarbital [5]. CNS effects of both compounds were tested on immature rats, age 14 days, in the developmental phase of quick morphological and functional growth. A marked difference in total locomotor activity, exploratory behaviour and reaction to both compounds between immature and adult rats is reported. Toxicity of RGH-3332 is favourable in itself and in comparison to that of phenobarbital in both age groups. CNS effects are neglibile compared to the main effect, they can be observed only in 6--8fold doses eliciting maximum inductive response in case of RGH-3332, while CNS effects are caused by phenobarbital at lower doses than that required for maximum inductive response.

Animals↗

PubMed2002

Phenylphenols, biphenols, bisphenol-A and 4-tert-octylphenol exhibit alpha and beta estrogen activities and antiandrogen activity in reporter cell lines.

We previously demonstrated the interactions of different chemical compounds with estrogen receptors ERalpha and ERbeta and the androgen receptor (AR) using different reporter cell lines. In this study, we characterize the ERalpha, ERbeta and AR activity of different biphenyls using the same tools. We provide evidence that several phenyl derivatives present both estrogenic and antiandrogenic activity. The extent of hydroxylation and the position of the hydroxyl function were important in determining their estrogenicity and antiandrogenicity. Of the tested compounds, bisphenol-A and 4,4' biphenol had very high estrogenic activity, although it was lower than that of the strong estrogenic alkylphenol, 4-tert-octylphenol. Bisphenol-A and 4,4' biphenol were able to activate ERs at concentrations lower than 1 microM, whereas the other compounds only activated at concentrations above 1 microM. Interestingly, 4,4' biphenol was a better agonist for ERbeta than for ERalpha. No androgenic activity was detected for any of these compounds. Bisphenol-A, 3-OH phenylphenol, 4-OH phenylphenol and 4,4' biphenol exhibited antiandrogenic activity close to that of 4-tert-octylphenol (IC(50) approximately 5 microM). In whole cell binding assays, these compounds displaced [3H] R1881 with Ki = 10 microM. Although these Ki values seem high in comparison with that of hydroxyflutamide (0.4 microM), one must keep in mind that environmental chemicals can accumulate in adipose tissues for several years. In conclusion, these environmental chemicals may have a negative impact on androgen action during fetal and post-natal life.

Androgen Receptor Antagonists↗

PubMed1999

Capillary solid-phase extraction-tandem mass spectrometry for fast quantification of free concentrations of tolterodine and two metabolites in ultrafiltered plasma samples.

A capillary solid-phase extraction (SPE) system has been coupled directly to electrospray tandem mass spectrometry for quantification of free tolterodine and metabolite concentrations in plasma. The unbound fraction of these compounds was obtained by ultrafiltration of plasma. The ultrafiltrate was directly injected onto the SPE capillary (4 mm x 200 microm, 5 microm C18). After desalting and clean-up of the sample, the analytes were eluted in backflush mode with methanol-1 mM triethylamine (70:30, v/v), providing considerable solute focusing. Elution from the SPE capillary was improved by inserting a short trapping capillary between the SPE capillary and the MS interface, by which analyte focusing was increased. The unresolved compounds eluted simultaneously with the remaining matrix compounds and were detected in a multiple-reaction monitoring (MRM) mode. No interference of the sample matrix on detection was observed, allowing aqueous standards to be used for calibration. Linear calibration curves were obtained between 0.05 and 1000 ng/ml (corresponding to 150 pM-3 microM) and the limit of detection was 50 pg/ml injecting 10 microl. Equilibration of the SPE capillary, sample loading, elution and detection took less then 6 min per sample.

Benzhydryl Compounds↗

PubMed2004

Beware of canine Gorilla Glue ingestions.

Household adhesive ingestions are considered relatively non-toxic. Gorilla Glue is a household glue containing a urethane polymer and a polymeric isocyanate liquid compound available in container sizes of 2 to 36 oz, and when applied will expand to 3-4 times its original volume. We report the ingestion of Gorilla Glue by 2 dogs that caused obstructive masses requiring surgical intervention. Dogs with a history of Gorilla Glue ingestion should be monitored closely by their owners and a veterinary referral made if signs of gastrointestinal distress develop.

Adhesives↗

PubMed2005

Quantification of urinary conjugates of bisphenol A, 2,5-dichlorophenol, and 2-hydroxy-4-methoxybenzophenone in humans by online solid phase extraction-high performance liquid chromatography-tandem mass spectrometry.

Urinary concentrations of phenols or their metabolites have been used as biomarkers to assess the prevalence of exposure to these compounds in the general population. Total urinary concentrations, which include both free and conjugated (glucuronide and sulfated) forms of the compounds, are usually reported. From a toxicologic standpoint, the relative concentrations of the free species compared with their conjugated analogs can be important because conjugation may reduce the potential biologic activity of the phenols. In this study, we determined the percentage of glucuronide and sulfate conjugates of three phenolic compounds, bisphenol A (BPA), 2,5-dichlorophenol (2,5-DCP), and 2-hydroxy-4-methoxybenzophenone (benzophenone-3, BP-3) in 30 urine samples collected between 2000 and 2004 from a demographically diverse group of anonymous adult volunteers. We used a sensitive on-line solid phase extraction-isotope dilution-high performance liquid chromatography-tandem mass spectrometry method. These three phenols were detected frequently in the urine samples tested. Only small percentages of the compounds (9.5% for BPA, and 3% for 2,5-DCP and BP-3) were excreted in their free form. The percentage of the sulfate conjugate was about twice that of the free compound. The glucuronide conjugate was the major metabolite, representing 69.5% (BPA), 89% (2,5-DCP), and 84.6% (BP-3) of the total amount excreted in urine. These results are in agreement with those reported before which suggested that BPA-glucuronide was an important BPA urinary metabolite in humans. To our knowledge, this is the first study describing the distribution of urinary conjugates of BP-3 and 2,5-DCP in humans.

Benzhydryl Compounds↗