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Toxicologic Pathology Dec 2020It is well established that hexachlorophene, which is used as an antibacterial agent, causes intramyelinic edema in humans and animal models. The hexachlorophene...
Qualitative and Quantitative Neuropathology Approaches Using Magnetic Resonance Microscopy (Diffusion Tensor Imaging) and Stereology in a Hexachlorophene Model of Myelinopathy in Sprague-Dawley Rats.
It is well established that hexachlorophene, which is used as an antibacterial agent, causes intramyelinic edema in humans and animal models. The hexachlorophene myelinopathy model, in which male Sprague-Dawley rats received 25 to 30 mg/kg hexachlorophene by gavage for up to 5 days, provided an opportunity to compare traditional neuropathology evaluations with magnetic resonance microscopy (MRM) findings. In addition, stereology assessments of 3 neuroanatomical sites were compared to quantitative measurements of similar structures by MRM. There were positive correlations between hematoxylin and eosin and luxol fast blue stains and MRM for identifying intramyelinic edema in the cingulum of corpus callosum, optic chiasm, anterior commissure (aca), lateral olfactory tracts, pyramidal tracts (py), and white matter tracts in the cerebellum. Stereology assessments were focused on the aca, longitudinal fasciculus of the pons, and py and demonstrated differences between control and treated rats, as was observed using MRM. The added value of MRM assessments was the ability to acquire qualitative 3-dimensional (3-D) images and obtain quantitative measurements of intramyelinic edema in 26 neuroanatomical sites in the intact brain. Also, diffusion tensor imaging (fractional anisotropy [FA]) indicated that there were changes in the cytoarchitecture of the white matter as detected by decreases in the FA in the treated compared to the control rats. This study demonstrates creative strategies that are possible using qualitative and quantitative assessments of potential white matter neurotoxicants in nonclinical toxicity studies. Our results lead us to the conclusion that volumetric analysis by MRM and stereology adds significant value to the standard 2-D microscopic evaluations.
Topics: Animals; Brain; Diffusion Tensor Imaging; Hexachlorophene; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Microscopy; Rats; Rats, Sprague-Dawley
PubMed: 33334257
DOI: 10.1177/0192623320968210 -
Canadian Medical Association Journal Jun 1973
Topics: Birth Weight; Brain; Burns; Central Nervous System; Hexachlorophene; Humans; Infant, Newborn; Infant, Premature; Skin Diseases; Staphylococcal Infections
PubMed: 4714869
DOI: No ID Found -
Scandinavian Journal of Work,... Oct 1995The evidence for reproductive disorders due to chemical exposure among hairdressers was evaluated. To this end, a literature study was conducted on Medline for the years... (Review)
Review
The evidence for reproductive disorders due to chemical exposure among hairdressers was evaluated. To this end, a literature study was conducted on Medline for the years 1985-1993. Reproductive disorders in humans were described for solvents such as ethanol and dichloromethane found mainly in hair sprays. Reproductive effects of several dye formulations, ethylene glycol ethers, nitrosamines, formaldehyde, hexachlorophene, and phthalic esters cannot be excluded, but few human data on low concentrations of these agents were available. Associations with menstrual disorders and spontaneous abortions were found in epidemiologic studies focused on hairdressers. Other studies showed inconsistent results, probably due to methodological shortcomings (misclassification of exposure, small sample sizes). It is concluded that there is little evidence for reproductive disorders among hairdressers to date. Limited availability of human data and unknown effects of chemical mixtures call for future research focused on human reproductive risks among hairdressers with emphasis on exposure assessment in the hairdressing salon.
Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Animals; Female; Hair Preparations; Humans; Infant, Newborn; Infertility, Female; Menstruation Disturbances; Netherlands; Occupational Diseases; Occupational Exposure; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors
PubMed: 8571088
DOI: 10.5271/sjweh.46 -
Environmental Health Perspectives Apr 1996Behavioral end points are being used with greater frequency in neurotoxicology to detect and characterize the adverse effects of chemicals on the nervous system.... (Review)
Review
Behavioral end points are being used with greater frequency in neurotoxicology to detect and characterize the adverse effects of chemicals on the nervous system. Behavioral measures are particularly important for neurotoxicity risk assessment since many known neurotoxicants do not result in neuropathology. The chlorinated hydrocarbon class consists of a wide variety of chemicals including polychlorinated biphenyls, clioquinol, trichloroethylene, hexachlorophene, organochlorine insecticides (DDT, dicofol, chlordecone,dieldrin, and lindane), and phenoxyherbicides. Each of these chemicals has effects on motor, sensory, or cognitive function that are detectable using functional measures such as behavior. Furthermore, there is evidence that if exposure occurs during critical periods of development, many of the chlorinated hydrocarbons are developmental neurotoxicants. Developmental neurotoxicity is frequently expressed as alterations in motor function or cognitive abilities or changes in the ontogeny of sensorimotor reflexes. Neurotoxicity risk assessment should include assessments of the full range of possible neurotoxicological effects, including both structural and functional indicators of neurotoxicity.
Topics: Behavior; Environmental Health; Humans; Hydrocarbons, Chlorinated; Insecticides; Nervous System Diseases; Neurotoxins; Risk Assessment; Toxicity Tests
PubMed: 9182042
DOI: 10.1289/ehp.96104s2353 -
British Medical Journal Nov 1977
Topics: Hexachlorophene; Humans; Infant Care; Infant, Newborn; Staphylococcal Infections
PubMed: 589189
DOI: 10.1136/bmj.2.6098.1353-b -
Antimicrobial Agents and Chemotherapy Jan 1985Bithionol, dichlorophene, and hexachlorophene, which are used in treating some helminthic infections, killed trophozoites of Giardia lamblia and Trichomonas vaginalis in...
Bithionol, dichlorophene, and hexachlorophene, which are used in treating some helminthic infections, killed trophozoites of Giardia lamblia and Trichomonas vaginalis in modified BI-S-33 and Asami media, respectively. Virtually all G. lamblia and T. vaginalis cells were killed within 24 h with a 0.42 mM concentration of these compounds, except that 0.93 mM dichlorophene was required for sterilizing T. vaginalis in the same period. In modified BI-S-33 and Asami media from which bovine and human sera were omitted, respectively, the inhibitory actions of the compounds against in vitro growth of these protozoa were significantly enhanced. Trophozoites of G. lamblia and T. vaginalis could be killed in shorter than 10 min with 0.074 mM dichlorophene and 0.0025 mM hexachlorophene, respectively, in serum-free media. G. lamblia, which was incubated in the complete medium containing dichlorophene, showed a characteristic swelling of the ventral side which led to disruption of the parasite, whereas bithionol caused a thin crack in the cytoplasm of T. vaginalis incubated in Asami medium. The crack appeared to enlarge and result in vacuolization of T. vaginalis. These observations suggest that bithionol, dichlorophene, and hexachlorophene merit further evaluation to ascertain whether they are useful for treatment of giardiasis and trichomoniasis.
Topics: Animals; Bithionol; Dichlorophen; Giardia; Hexachlorophene; Phenols; Trichomonas vaginalis
PubMed: 3872626
DOI: 10.1128/AAC.27.1.65 -
Viruses Apr 2019Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe disease in humans with case-fatality rates of up to...
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe disease in humans with case-fatality rates of up to 30%. There are currently very limited treatment options for SFTSV infection. We conducted a drug repurposing program by establishing a two-tier test system to rapidly screen a Food and Drug Administration- (FDA)-approved drug library for drug compounds with anti-SFTSV activity in vitro. We identified five drug compounds that inhibited SFTSV replication at low micromolar concentrations, including hexachlorophene, triclosan, regorafenib, eltrombopag, and broxyquinoline. Among them, hexachlorophene was the most potent with an IC of 1.3 ± 0.3 µM and a selectivity index of 18.7. Mechanistic studies suggested that hexachlorophene was a virus entry inhibitor, which impaired SFTSV entry into host cells by interfering with cell membrane fusion. Molecular docking analysis predicted that the binding of hexachlorophene with the hydrophobic pocket between domain I and domain III of the SFTSV Gc glycoprotein was highly stable. The novel antiviral activity and mechanism of hexachlorophene in this study would facilitate the use of hexachlorophene as a lead compound to develop more entry inhibitors with higher anti-SFTSV potency and lower toxicity.
Topics: Antiviral Agents; Benzoates; Bunyaviridae Infections; Drug Approval; Drug Discovery; Drug Repositioning; Hydrazines; Inhibitory Concentration 50; Molecular Docking Simulation; Phlebovirus; Pyrazoles; Small Molecule Libraries; Triclosan; United States; United States Food and Drug Administration; Virus Internalization
PubMed: 31027241
DOI: 10.3390/v11040385 -
Tissue Engineering and Regenerative... Apr 2018The hexachlorophene (HCP) is a highly lipophilic chlorinated bisphenol present in hygienic and dermatological products. The HCP accumulates preferentially in adipose...
The hexachlorophene (HCP) is a highly lipophilic chlorinated bisphenol present in hygienic and dermatological products. The HCP accumulates preferentially in adipose tissue that is a privileged source of mesenchymal stem cells (MSCs). The evaluation of the potential effects of HCP on MSCs is important for their medical application. Here we examined the effects of HCP on murine adipose tissue-derived stem cells (ADSCs) and human umbilical cord-derived stem cells (UCSCs) in cell culture. We found that 10 and 10 M HCP inhibits proliferation, osteogenesis and increases apoptosis of ADSCs and UCSCs. While the effect of HCP on proliferation and differentiation potential of these two cell lines was similar, the UCSCs appeared much more resistant to HCP-induced apoptosis than ADSCs. These results suggest that the adipose tissue-derived ADSCs have higher sensitive for HCP than umbilical cord-derived UCSCs and indicate that the umbilical cord can be a preferable source of MSCs for prospective medical applications in the future.
PubMed: 30603548
DOI: 10.1007/s13770-017-0103-9 -
Neurobiology of Disease Feb 2015Aβ accumulation plays a central role in the pathogenesis of Alzheimer's disease (AD). Recent studies suggest that the process of Aβ nucleated polymerization is...
Aβ accumulation plays a central role in the pathogenesis of Alzheimer's disease (AD). Recent studies suggest that the process of Aβ nucleated polymerization is essential for Aβ fibril formation, pathology spreading and toxicity. Therefore, targeting this process represents an effective therapeutic strategy to slow or block disease progression. To discover compounds that might interfere with the Aβ seeding capacity, toxicity and pathology spreading, we screened a focused library of FDA-approved drugs in vitro using a seeding polymerization assay and identified small molecule inhibitors that specifically interfered with Aβ seeding-mediated fibril growth and toxicity. Mitoxantrone, bithionol and hexachlorophene were found to be the strongest inhibitors of fibril growth and protected primary cortical neuronal cultures against Aβ-induced toxicity. Next, we assessed the effects of these three inhibitors in vivo in the mThy1-APPtg mouse model of AD (8-month-old mice). We found that mitoxantrone and bithionol, but not hexachlorophene, stabilized diffuse amyloid plaques, reduced the levels of Aβ42 oligomers and ameliorated synapse loss, neuronal damage and astrogliosis. Together, our findings suggest that targeting fibril growth and Aβ seeding capacity constitutes a viable and effective strategy for protecting against neurodegeneration and disease progression in AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Bithionol; Cells, Cultured; Cerebral Cortex; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Gliosis; Hexachlorophene; Humans; Mice, Inbred C57BL; Mice, Transgenic; Mitoxantrone; Nerve Degeneration; Neurons; Neuroprotective Agents; Peptide Fragments; Plaque, Amyloid; Rats
PubMed: 25173807
DOI: 10.1016/j.nbd.2014.08.017 -
British Medical Journal Apr 1977
Topics: Hexachlorophene; Humans; Infant; Infant, Newborn; Skin Diseases
PubMed: 851778
DOI: 10.1136/bmj.1.6065.904-c