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Fulltext Tualang Honey Protects against BPA-Induced Morphological Abnormalities and Disruption of ERα, ERβ, and C3 mRNA and Protein Expressions in the Uterus of Rats

Mohamad Zaid SS, Kassim NM, Othman S

Evid Based Complement Alternat Med, 2015;2015:202874.
PMID: 26788107 DOI: 10.1155/2015/202874

Bisphenol A (BPA) is an endocrine disrupting chemical (EDC) that can disrupt the normal functions of the reproductive system. The objective of the study is to investigate the potential protective effects of Tualang honey against BPA-induced uterine toxicity in pubertal rats. The rats were administered with BPA by oral gavage over a period of six weeks. Uterine toxicity in BPA-exposed rats was determined by the degree of the morphological abnormalities, increased lipid peroxidation, and dysregulated expression and distribution of ERα, ERβ, and C3 as compared to the control rats. Concurrent treatment of rats with BPA and Tualang honey significantly improved the uterine morphological abnormalities, reduced lipid peroxidation, and normalized ERα, ERβ, and C3 expressions and distribution. There were no abnormal changes observed in rats treated with Tualang honey alone, comparable with the control rats. In conclusion, Tualang honey has potential roles in protecting the uterus from BPA-induced toxicity, possibly accounted for by its phytochemical properties.

Matched MeSH terms: Endocrine Disruptors
Assessment of organochlorine pesticides and plasticisers in the Selangor River basin and possible pollution sources

Santhi VA, Mustafa AM

Environ Monit Assess, 2013 Feb;185(2):1541-54.
PMID: 22552495 DOI: 10.1007/s10661-012-2649-2

A study on the quality of water abstracted for potable use was conducted in the Selangor River basin from November 2008 to July 2009. Seven sampling sites representing the intake points of water treatment plants in the basin were selected to determine the occurrence and level of 15 organochlorine pesticides (OCPs), six phthalate esters (PAEs) and bisphenol A (BPA). Results indicated OCPs were still detected regularly in 66.1 % of the samples with the Σ(15)OCPs ranging from 0.6-25.2 ng/L. The first data on PAEs contamination in the basin revealed Σ(6)PAEs concentrations were between 39.0 and 1,096.6 ng/L with a median concentration of 186.0 ng/L while BPA concentration ranged from <1.2 to 120.0 ng/L. Although di-n-butyl phthalate was detected in all the samples, concentrations of di-ethyl(hexyl)phthalate were higher. Sampling sites located downstream recorded the highest concentrations, together with samples collected during the dry season. Comparison of the detected contaminants with the Department of Environment Water Quality Index (DOE-WQI) showed some agreement between the concentration and the current classification of stream water. While the results suggest that the sites were only slightly polluted and suitable to be used as drinking water source, its presence is cause for concern especially to the fragile firefly "Pteroptyx tener" ecosystem located further downstream.

Matched MeSH terms: Endocrine Disruptors/analysis
Reactive oxygen species and glutathione antioxidants in the testis of the soil biosentinel Podarcis sicula (Rafinesque 1810)

Guerriero G, D'Errico G, Di Giaimo R, Rabbito D, Olanrewaju OS, Ciarcia G

Environ Sci Pollut Res Int, 2018 Jul;25(19):18286-18296.
PMID: 28936697 DOI: 10.1007/s11356-017-0098-8

Important toxicological achievements have been made during the last decades using reptiles. We focus our investigation on gonadal reproductive health of the soil biosentinel Podarcis sicula which is very sensitive to endocrine-disrupting chemicals. The aim of this study is to quantitatively detect, by sensitive microassays, reactive oxygen species and the glutathione antioxidants in the testis and investigate if they are differentially expressed before and after remediation of a site of the "Land of Fires" (Campania, Italy) subject to illicit dumping of unknown material. The oxidative stress level was evaluated by electron spin resonance spectroscopy applying a spin-trapping procedure able to detect products of lipid peroxidation, DNA damage and repair by relative mobility shift, and poly(ADP-ribose) polymerase enzymatic activity, respectively, the expression of glutathione peroxidase 4 transcript by real-time quantitative PCR analysis, the antioxidant glutathione S-transferase, a well-assessed pollution index, by enzymatic assay and the total soluble antioxidant capacity. Experimental evidences from the different techniques qualitatively agree, thus confirming the robustness of the combined experimental approach. Collected data, compared to those from a reference unpolluted site constitute evidence that the reproductive health of this lizard is impacted by pollution exposure. Remediation caused significant reduction of reactive oxygen species and downregulation of glutathione peroxidase 4 mRNAs in correspondence of reduced levels of glutathione S-transferase, increase of antioxidant capacity, and repair of DNA integrity. Taken together, our results indicate directions to define new screening approaches in remediation assessment.

Matched MeSH terms: Endocrine Disruptors/toxicity
Sources, mechanisms, and fate of steroid estrogens in wastewater treatment plants: a mini review

Ting YF, Praveena SM

Environ Monit Assess, 2017 Apr;189(4):178.
PMID: 28342046 DOI: 10.1007/s10661-017-5890-x

Steroid estrogens, such as estrone (E1), 17β-estradiol (E2), estriol (E3), and 17α-ethinylestradiol (EE2), are natural and synthetic hormones released into the environment through incomplete sewage discharge. This review focuses on the sources of steroid estrogens in wastewater treatment plants (WWTPs). The mechanisms and fate of steroid estrogens throughout the entire wastewater treatment system are also discussed, and relevant information on regulatory aspects is given. Municipal, pharmaceutical industry, and hospitals are the main sources of steroid estrogens that enter WWTPs. A typical WWTP comprises primary, secondary, and tertiary treatment units. Sorption and biodegradation are the main mechanisms for removal of steroid estrogens from WWTPs. The fate of steroid estrogens in WWTPs depends on the types of wastewater treatment systems. Steroid estrogens in the primary treatment unit are removed by sorption onto primary sludge, followed by sorption onto micro-flocs and biodegradation by microbes in the secondary treatment unit. Tertiary treatment employs nitrification, chlorination, or UV disinfection to improve the quality of the secondary effluent. Activated sludge treatment systems for steroid estrogens exhibit a removal efficiency of up to 100%, which is higher than that of the trickling filter treatment system (up to 75%). Moreover, the removal efficiency of advance treatment systems exceeds 90%. Regulatory aspects related to steroid estrogens are established, especially in the European Union. Japan is the only Asian country that implements a screening program and is actively involved in endocrine disruptor testing and assessment. This review improves our understanding of steroid estrogens in WWTPs, proposes main areas to be improved, and provides current knowledge on steroid estrogens in WWTPs for sustainable development.

Matched MeSH terms: Endocrine Disruptors/analysis
Fulltext Protective role of Mas Cotek (Ficus deltoidea) against the toxic effects of bisphenol A on morphology and sex steroid receptor expression in the rat uterus

Zaid SSM, Othman S, Kassim NM

Biomed Pharmacother, 2021 Aug;140:111757.
PMID: 34044283 DOI: 10.1016/j.biopha.2021.111757

BACKGROUND: Numerous scientific studies have found that young women are at a high risk of reproductive infertility due to their routine exposure to numerous bisphenol A (BPA) products. This risk is highly associated with the production of reactive oxygen species from BPA products. Ficus deltoidea, which has strong antioxidant properties, was selected as a potential protective agent to counter the detrimental effects of BPA in the rat uterus.
METHODS: Female Sprague-Dawley rats were allocated into four groups (n = 8) as follows: (i) the Normal Control group (NC), (ii) the BPA-exposed group (PC), (iii) the group concurrently treated with BPA and F. deltoidea (FC) and (iv) the group treated with F. deltoidea alone (F).
RESULTS: After 6 weeks of concurrent treatment with F. deltoidea, uterine abnormalities in the BPA-exposed rats showed a significant improvement. Specifically, the size of stromal cells increased; interstitial spaces between stromal cells expanded; the histology of the glandular epithelium and the myometrium appeared normal and mitotic figures were present. The suppressive effects of BPA on the expression levels of sex steroid receptors (ERα and ERβ) and the immunity gene C3 were significantly normalised by F. deltoidea treatment. The role of F. deltoidea as an antioxidant agent was proven by the significant reduction in malondialdehyde level in BPA-exposed rats. Moreover, in BPA-exposed rats, concurrent treatment with F. deltoidea could normalise the level of the gonadotropin hormone, which could be associated with an increase in the percentage of rats with a normal oestrous cycle.
CONCLUSION: F. deltoidea has the potential to counter the toxic effects of BPA on the female reproductive system. These protective effects might be due to the phytochemical properties of F. deltoidea. Therefore, future study is warranted to identify the bioactive components that contribute to the protective effects of F. deltoidea.

Matched MeSH terms: Endocrine Disruptors/toxicity*
Occurrence and level of emerging organic contaminant in fish and mollusk from Klang River estuary, Malaysia and assessment on human health risk

Omar TFT, Aris AZ, Yusoff FM, Mustafa S

Environ Pollut, 2019 May;248:763-773.
PMID: 30851586 DOI: 10.1016/j.envpol.2019.02.060

The occurrence, level, and distribution of multiclass emerging organic contaminants (EOCs) in fish and mollusks from the Klang River estuary were examined. The targeted EOCs for this assessment were phenolic endocrine disrupting compounds (bisphenol A, 4-OP, and 4-NP), organophosphorous pesticides (quinalphos, chlorpyrifos, and diazinon), estrogenic hormones (E2, E1, and EE2), and pharmaceutically active chemicals (primidone, sulfamethoxazole, dexamethasone, diclofenac, amoxicillin, progesterone, and testosterone). Results from this study showed that the prevalent contamination of the Klang River estuary by EOCs with diclofenac, bisphenol A, progesterone, and amoxicillin were predominantly detected in fish and mollusks. Among the EOCs, diclofenac and progesterone had the highest concentrations in fish and mollusk samples, respectively. The concentrations of diclofenac and progesterone in fish and mollusk samples range from 1.42 ng/g to 10.76 ng/g and from 0.73 ng/g to 9.57 ng/g, respectively. Bisphenol A should also be highlighted because of its significant presence in both fish and mollusks. The concentration of bisphenol A in both matrices range from 0.92 ng/g to 5.79 ng/g. The calculated hazard quotient (HQ) for diclofenac, bisphenol A, and progesterone without consideration to their degradation byproduct were less than one, thus suggesting that the consumption of fish and mollusks from the Klang River estuary will unlikely pose any health risk to consumers on the basis of the current assessment. Nonetheless, this preliminary result is an important finding for pollution studies in Malaysian tropical coastal ecosystems, particularly for organic micropollutant EOCs, and can serve as a baseline database for future reference.

Matched MeSH terms: Endocrine Disruptors
Therapeutic effect of pectin on octylphenol induced kidney dysfunction, oxidative stress and apoptosis in rats

Koriem KM, Arbid MS, Emam KR

Environ Toxicol Pharmacol, 2014 Jul;38(1):14-23.
PMID: 24860957 DOI: 10.1016/j.etap.2014.04.029

Octylphenol (OP) is one of ubiquitous pollutants in the environment. It belongs to endocrine-disrupting chemicals (EDC). It is used in many industrial and agricultural products. Pectin is a family of complex polysaccharides that function as a hydrating agent and cementing material for the cellulose network. The aim of this study was to evaluate the therapeutic effect of pectin in kidney dysfunction, oxidative stress and apoptosis induced by OP exposure. Thirty-two male albino rats were divided into four equal groups; group 1 control was injected intraperitoneally (i.p) with saline [1 ml/kg body weight (bwt)], groups 2, 3 & 4 were injected i.p with OP (50 mg/kg bwt) three days/week over two weeks period where groups 3 & 4 were injected i.p with pectin (25 or 50 mg/kg bwt) three days/week over three weeks period. The results of the present study revealed that OP significantly decreased glutathione-S-transferase (GST), glutathione peroxidase (GPx), catalase (CAT), reduced glutathione (GSH), glutathione reductase (GR) and superoxide dismutase (SOD) levels while increased significantly lipid peroxidation (MDA), nitric oxide (NO) and protein carbonyls (PC) levels in the kidney tissues. On the other hand, OP increased serum urea and creatinine. Furthermore, OP increased significantly serum uric acid but decreased significantly the kidney weight. Moreover, OP decreased p53 expression while increased bcl-2 expression in the kidney tissue. The treatment with either dose of pectin to OP-exposed rats restores all the above parameters to approach the normal values where pectin at higher dose was more effective than lower one. These results were supported by histopathological investigations. In conclusion, pectin has antioxidant and anti-apoptotic activities in kidney toxicity induced by OP and the effect was dose-dependent.

Matched MeSH terms: Endocrine Disruptors/toxicity*
Bisphenol A exposure disturbs the bone metabolism: An evolving interest towards an old culprit

Thent ZC, Froemming GRA, Muid S

Life Sci, 2018 Apr 01;198:1-7.
PMID: 29432759 DOI: 10.1016/j.lfs.2018.02.013

Bisphenol A (BPA) (2,2,-bis (hydroxyphenyl) propane), a well-known endocrine disruptor (ED), is the exogenous chemical that mimic the natural endogenous hormone like oestrogen. Due to its extensive exposure to humans, BPA is considered to be a major toxicological agent for general population. Environmental exposure of BPA results in adverse health outcomes including bone loss. BPA disturbs the bone health by decreasing the plasma calcium level and inhibiting the calcitonin secretion. BPA also stimulated differentiation and induced apoptosis in human osteoblasts and osteoclasts. However, little is known about the underlying mechanisms of the untoward effect of BPA against bone metabolism. The present review gives an overview on the possible mechanisms of BPA towards bone loss. The previous literature shows that BPA exerts its toxic effect on bone cells by binding to the oestrogen related receptor-gamma (ERγ), reducing the bone morphogenic protein-2 (BMP-2) and alkaline phosphatase (ALP) activities. BPA interrupts the bone metabolism via RANKL, apoptosis and Wnt/β-catenin signaling pathways. It is, however, still debated on the exact underlying mechanism of BPA against bone health. We summarised the molecular evidences with possible mechanisms of BPA, an old environmental culprit, in bone loss and enlightened the underlying understanding of adverse action of BPA in the society.

Matched MeSH terms: Endocrine Disruptors/adverse effects
Fulltext A Review on the Effects of Bisphenol A and Its Derivatives on Skeletal Health

Chin KY, Pang KL, Mark-Lee WF

Int J Med Sci, 2018;15(10):1043-1050.
PMID: 30013446 DOI: 10.7150/ijms.25634

Bisphenol A (BPA) is an endocrine disruptor which can bind to the oestrogen receptor. It also possesses oestrogenic, antiandrogenic, inflammatory and oxidative properties. Since bone responds to changes in sex hormones, inflammatory and oxidative status, BPA exposure could influence bone health in humans. This review aimed to summarize the current evidence on the relationship between BPA and bone health derived from cellular, animal and human studies. Exposure to BPA (0.5-12.5 µM) decreased the proliferation of osteoblast and osteoclast precursor cells and induce their apoptosis. Bisphenol AF (10 nM) enhanced transforming growth factor beta signalling but bisphenol S (10 nM) inhibited Wnt signalling involved in osteoblast differentiation in vitro. In animals, BPA and its derivatives demonstrated distinct effects in different models. In prenatal/postnatal exposure, BPA increased femoral bone mineral content in male rats (at 25 ug/kg/day) but decreased femoral mechanical strength in female mice (at 10 µg/kg/day). In oestrogen deficiency models, BPA improved bone mineral density and microstructures in aromatase knockout mice (at very high dose, 0.1% or 1.0% w/w diet) but decreased trabecular density in ovariectomized rats (at 37 or 370 ug/kg/day). In contrast, bisphenol A diglycidyl ether (30 mg/kg/day i.p.) improved bone health in normal male and female rodents and decreased trabecular separation in ovariectomized rodents. Two cross-sectional studies have been performed to examine the relationship between BPA level and bone mineral density in humans but they yielded negligible association. As a conclusion, BPA and its derivatives could influence bone health and a possible gender effect was observed in animal studies. However, its effects in humans await verification from more comprehensive longitudinal studies in the future.

Matched MeSH terms: Endocrine Disruptors