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Start Over Topic animal experimentation Topic descriptive statistics Topic dose-effect relationship in pharmacology Topic research funding Database Academic Search Index
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1. Rapid Responses and Mechanism of Action for Low-Dose Bisphenol S on ex Vivo Rat Hearts and Isolated Myocytes: Evidence of Female-Specific Proarrhythmic Effects.

Author

Gao, Xiaoqian, Ma, Jianyong, Chen, Yamei, and Wang, Hong-Sheng

Subjects
*BISPHENOLS, *TOXICITY testing, *CONFOCAL fluorescence microscopy, *PERFUSION, *PROARRHYTHMIA, *DISEASE risk factors, *ANIMAL experimentation, *ARRHYTHMIA, *CALCIUM, *CHI-squared test, *DENTAL resins, *DOSE-effect relationship in pharmacology, *ELECTROCARDIOGRAPHY, *ELECTROPHYSIOLOGY, *HEART, *IMMUNOBLOTTING, *RESEARCH methodology, *MOLECULAR structure, *PHENOLS, *RATS, *RESEARCH funding, *STATISTICS, *T-test (Statistics), *TISSUE culture, *DATA analysis, *DATA analysis software, *DESCRIPTIVE statistics, *ONE-way analysis of variance
Abstract

Background: Bisphenol S (BPS) has increasingly been used as a substitute for bisphenol A (BPA) in some “BPA-free” consumer goods and in thermal papers. Wide human exposure to BPS has been reported; however, the biological and potential toxic effects of BPS are poorly understood. Objective: In this study, we sought to elucidate the sex-specific rapid effect of BPS in rat hearts and its underlying mechanism. Methods: We examined the rapid effects of BPS in rat hearts using electrophysiology, confocal and conventional fluorescence imaging, and immunoblotting. Treatment was administered via acute perfusion of excised hearts or isolated cardiac myocytes. Results: In female rat hearts acutely exposed to 10-9 M BPS, the heart rate was increased; in the presence of catecholamine-induced stress, the frequency of ventricular arrhythmia events was markedly increased. BPS-exposed hearts showed increased incidence of arrhythmogenic-triggered activities in female ventricular myocytes and altered myocyte Ca2+ handling, particularly spontaneous Ca2+ release from the sarcoplasmic reticulum. The dose responses of BPS actions were inverted U‑shaped. The impact of BPS on myocyte Ca2+ handling was mediated by estrogen receptor β signaling and by rapid increases in the phosphorylation of key Ca2+ handling proteins, including ryanodine receptor and phospholamban. The proarrhythmic effects of BPS were female specific; male rat hearts were not affected by BPS at the organ, myocyte, or protein levels. Conclusion: Rapid exposure to low-dose BPS showed proarrhythmic impact on female rat hearts; these effects at the organ, cellular, and molecular levels are remarkably similar to those reported for BPA. Evaluation of the bioactivity and safety of BPS and other BPA analogs is necessary before they are used as BPA alternatives in consumer products. Citation: Gao X, Ma J, Chen Y, Wang HS. 2015. Rapid responses and mechanism of action for low-dose bisphenol S on ex vivo rat hearts and isolated myocytes: evidence of female-specific proarrhythmic effects. Environ Health Perspect 123:571-578; [ABSTRACT FROM AUTHOR]

Published
2015
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2. Antimicrobial, Antioxidative, and Insect Repellent Effects of Artemisia absinthium Essential Oil.

Author

Mihajilov-Krstev, Tatjana, Jovanović, Boris, Jović, Jovana, Ilić, Budimir, Miladinović, Dragoljub, Matejić, Jelena, Rajković, Jelena, Đorđević, Ljubiša, Cvetković, Vladimir, and Zlatković, Bojan

Subjects
*THERAPEUTIC use of essential oils, *ANIMAL experimentation, *ANTI-infective agents, *ANTIOXIDANTS, *CHI-squared test, *DOSE-effect relationship in pharmacology, *ESSENTIAL oils, *GAS chromatography, *INSECT baits & repellents, *LONGITUDINAL method, *MASS spectrometry, *MEDICINAL plants, *MICROBIOLOGICAL techniques, *PROBABILITY theory, *RESEARCH funding, *TOXICITY testing, *DESCRIPTIVE statistics
Abstract

In this paper, the chemical composition and biological activity of the essential oil of Artemisia absinthium was studied. The aim of this study was to investigate the potential of ethnopharmacological uses of this plant species in the treatment of gastrointestinal diseases and wounds, and as an insect repellent. The aerial part of the plant was hydrodistilled, and the chemical composition of the essential oil was analyzed by gas chromatography and gas chromatography/mass spectrometry. Forty-seven compounds, corresponding to 94.65% of the total oil, were identified, with the main constituents being sabinene (24.49%), sabinyl acetate (13.64%), and α-phellandrene (10.29%). The oil yield was 0.23% (v/w). The antimicrobial activity of the oil was investigated against ten bacterial isolates (from patients wounds and stools) and seven American Type Culture Collection strains using a microwell dilution assay. The minimal inhibitory/bactericidal concentration of the oil ranged from <0.08 to 2.43 mg/mL and from 0.08 to 38.80 mg/mL, respectively. The antioxidant activity of the essential oil was evaluated using 2,2-diphenyl-1-picrylhydrazil and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical-scavenging methods and assessed as significant. Skin irritation potential and acute toxicity of the oil were also investigated. Results of the skin irritant reaction showed that none of the 30 volunteers developed a positive skin irritant reaction to undiluted A. absinthium essential oil. Acute oral exposure to the essential oil did not cause mortality in the treated mice, but it did cause neurological, muscle, and gastrointestinal problems. A subchronic toxicity test on Drosophila melanogaster showed that the essential oil of A. absinthium is toxic for developing insect larvae. Starting with the concentration of 0.38% of essential oil in medium, significant mortality of larvae exposed to the oil was noted when compared to the control. Probit analysis revealed that the LC50 value of A. absinthium essential oil for D. melanogaster larvae after 15 days of exposure was 6.31 % (49 mg/mL). The essential oil also affected the development of D. melanogaster larvae and significantly delayed achievement of the pupa stadium. [ABSTRACT FROM AUTHOR]

Published
2014
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3. Myocardial lipidomics profiling delineate the toxicity of traditional Chinese medicine Aconiti Lateralis radix praeparata.

Author

Cai, Yamei, Gao, Yue, Tan, Guangguo, Wu, Si, Dong, Xin, Lou, Ziyang, Zhu, Zhenyu, and Chai, Yifeng

Subjects
*LIPID metabolism, *HEART analysis, *MEDICINAL plants, *ALTERNATIVE medicine, *ANIMAL experimentation, *ARRHYTHMIA, *BIOMARKERS, *BIOCHEMISTRY, *BIOPHYSICS, *COMPARATIVE studies, *DOSE-effect relationship in pharmacology, *DRUG toxicity, *ELECTROCARDIOGRAPHY, *HISTOLOGICAL techniques, *LIQUID chromatography, *MASS spectrometry, *PHENOMENOLOGY, *RESEARCH methodology, *LIPID peroxidation (Biology), *MICE, *MYOCARDIUM, *PHOSPHOLIPIDS, *RESEARCH funding, *PLANT roots, *T-test (Statistics), *PLANT extracts, *PILOT projects, *STATISTICAL significance, *DATA analysis software, *DESCRIPTIVE statistics
Abstract

Abstract: Ethnopharmacological relevance: The lateral root of Aconitum has been popularly used in traditional Chinese medicine (TMC) known as Fuzi which is beneficial for the treatment of various diseases, such as rheumatism, painful joints, syncope and bronchial asthma. However, it has a potential carditoxicity with a relatively narrow margin of safety. Aim of the study: This paper was designed to explore the mechanisms of Fuzi's toxicity and find out potential tissue-specific biomarkers of toxic effects. Material and methods: A myocardial lipidomics based on ultraperformance lipid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC/Q-TOF MS) was developed to compare three cardiac lipid extraction methods and investigate the changes of lipids in mice heart of three different dosage groups. In addition, we concurrently inspected the biochemical parameters in plasma, observed the histology of the heart and recorded the electrocardiogram (ECG). Results: The cardiotoxicity of Fuzi was dose-dependent, and the high-dose group obviously manifested the heart damage in histology and a certain degree of arrhythmia. Significant changes of 14 lipid metabolites which primarily involved in phospholipid metabolism, sphingolipid metabolism, saturated fatty acid oxidation and unsaturated fatty acid peroxidation were identified and considered as the potential biomarkers of Fuzi toxicity. Conclusion: The lipidomics approach is helpful to search potential tissue-specific biomarkers and understand the underlying mechanisms of Fuzi toxicity on the heart. [Copyright &y& Elsevier]

Published
2013
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4. Aurantio-Obtusin Stimulates Chemotactic Migration and Differentiation of MC3T3-E1 Osteoblast Cells.

Author

Vishnuprasad, Chethala N., Tomoko Tsuchiya, Shiro Kanegasaki, Joon Ho Kim, and Sung Soo Han

Subjects
*ALKALINE phosphatase, *ALTERNATIVE medicine, *ANIMAL experimentation, *BIOLOGICAL models, *CONNECTIVE tissue cells, *DOSE-effect relationship in pharmacology, *MEDICINAL plants, *MICE, *RESEARCH funding, *STATISTICAL hypothesis testing, *T-test (Statistics), *PLANT extracts, *DESCRIPTIVE statistics, *IN vitro studies, *PHYSIOLOGY
Abstract

Osteoporosis is one of the major metabolic bone diseases and is among the most challenging non-communicable diseases to treat. Although there is an increasing interest in identifying bioactive molecules for the prevention and management of osteoporosis, such studies principally focus only on differentiation and mineralization of osteoblasts or inhibition of osteoclast activity. Stimulation of osteoblast migration must be a promising osteoanabolic strategy for improved metabolic bone disease therapy. In this study, we show that an anthraquinone derivative, aurantio-obtusin, stimulated chemotactic migration of MC3T3-E1 osteoblast cells in a concentration-dependent manner. The use of a real-time chemotaxis analyzing system, TAXIScan, facilitated the evaluation of both velocity and directionality of osteoblast migration in response to the compound. Besides migration, the compound stimulated osteoblast differentiation andmineralization. Taken together, the data presented in this paper demonstrate that aurantio-obtusin is a promising osteoanabolic compound of natural origin with potential therapeutic applications in the prevention of osteoporosis and other metabolic bone diseases. [ABSTRACT FROM AUTHOR]

Published
2014
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