Oral exposure to low-dose bisphenol A induces hyperplasia of dorsolateral prostate and upregulates EGFR expression in adult Sprague-Dawley rats

2019 ◽  
Vol 35 (10) ◽  
pp. 647-659 ◽  
Author(s):  
Shuangshuang Wu ◽  
Dongyan Huang ◽  
Xin Su ◽  
Han Yan ◽  
Jianhui Wu ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Low Dose ◽  
Synergetic Effect ◽  
Oral Exposure ◽  
Signal Pathways ◽  
Sprague Dawley ◽  
Sd Rats ◽  
Egfr Expression ◽  
Endocrine Hormone ◽  
Prostate Diseases

Prostate is sensitive to endocrine hormone level, and the synergetic effect of estrogen and androgen is critical in prostate growth. The change of signal pathways caused by the imbalance of estrogen and androgen might function in the occurrence of prostate diseases. As a well-known endocrine disruptor compound, bisphenol A (BPA) can disturb the normal function of endocrine hormone and affect prostate development. This study aims to investigate effects of BPA on the dorsolateral prostate (DLP) and the related gene expression of the tissue in adult Sprague- Dawley (SD) rats and to explore the mechanism for the effect of low-dose BPA on DLP hyperplasia. Three-month-old male SD rats were treated with BPA (10.0, 30.0, or 90.0 µg (kg.day)−1, gavage) or vehicle (gavage) for 4 weeks. BPA significantly increased the DLP weight, the DLP organ coefficient, and the prostate epithelium height ( p < 0.01) of rats dose-dependently. Microarray analysis and quantitative real-time polymerase chain reaction showed that BPA significantly upregulated the transcriptional levels of some genes, including pituitary tumor transforming gene 1, epidermal growth factor, Sh3kbp1, and Pcna. Furthermore, the expression of PCNA ( p < 0.01), androgen receptor ( p < 0.01), and EGF receptor (EGFR) ( p < 0.001) in DLP was increased significantly by BPA treatment, and the expression of estrogen receptor alpha was also upregulated. The findings evidenced that low-dose BPA could induce DLP hyperplasia in adult rats, and the upregulated EGF/EGFR pathway that was responsive to estrogen and androgen might play an essential role in the DLP hyperplasia induced by low-dose BPA.

Ferulic Acid Dose Effect on Pharmacokinetics of Glimepiride and its Metabolite Hydroxy Glimepiride in Rats

2021 ◽  
Vol 17 ◽  
Author(s):  
Yuxian Lin ◽  
Faxin Sun ◽  
Jinlai Liu ◽  
Qinghua Weng ◽  
Lijun Jin ◽  
...  
Keyword(s):  
Ferulic Acid ◽  
Low Dose ◽  
Dose Effect ◽  
High Dose ◽  
Intragastric Administration ◽  
Healthy Male ◽  
Sprague Dawley ◽  
Sd Rats ◽  
High Dose Treatment ◽  
Significant Difference

Background: To mitigate diabetes and its complications in cardiovascular diseases, the antidiabetic agent glimepiride is usually administered with ferulic acid concomitantly in clinics. However, both drugs are prone to be metabolized partly by CYP2C9, thus they have the potential drug-drug interaction affecting the safety and efficacy. Objective: This project aimed to evaluate the pharmacokinetic (PK) effects of ferulic acid (FA) on glimepiride (GLM) and its metabolite hydroxy glimepiride (OH-GLM) in plasma by using the HPLC-MS/MS method. Methods: Healthy male Sprague Dawley (SD) rats were randomly divided into three groups. They received intragastric administration of 0.5% sodium carboxymethyl cellulose (CMC), low-dose FA (20 mg•kg-1), and high-dose FA (40 mg•kg-1) for 8 days, respectively. Rats were given 0.5% sodium CMC or FA on the last day and then uniformly given 1.0 mg•kg-1 glimepiride by gavage. Blood samples were obtained from retro-orbital plexus at the time points of 0.167, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after administration. Plasma samples were analyzed for GLM and its metabolite OH-GLM on an HPLC-MS/MS system. Results: No statistically significant difference was found in the effect of low-dose FA on the pharmacokinetics of GLM. High-dose FA significantly decreased Cmax of GLM by 30.05% and CLz/F of OH-GLM by 47.45%. It also increased Tmax and t1/2z of GLM by 95.87% and 140.00%. Conclusion: Low-dose FA did not alter GLM metabolism, while high-dose treatment of FA caused pharmacokinetics interaction with GLM in rats.

Perinatal oral exposure to low doses of bisphenol A, S or F impairs gut barrier and immune functions in female offspring mice

2019 ◽  
Author(s):  
Yann Malaisé ◽  
Corinne Lencina ◽  
Christel Cartier ◽  
Maïwenn Olier ◽  
Sandrine Ménard ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Immune Responses ◽  
Bisphenol A ◽  
Low Dose ◽  
Intestinal Barrier ◽  
Female Offspring ◽  
Oral Exposure ◽  
Gut Barrier ◽  
Cellular Immune Responses ◽  
Cellular Immune

Abstract Background Bisphenol A (BPA), one of the highest-volume chemicals produced worldwide, has been identified as an endocrine disruptor. Many peer-reviewing studies have reported adverse effects of low dose BPA exposure, particularly during perinatal period (gestation and/or lactation). We previously demonstrated that perinatal oral exposure to BPA (via gavage of mothers during gestation and lactation) has long-term consequences on immune response and intestinal barrier functions. Due to its adverse effects on several developmental and physiological processes, BPA was removed from consumer products and replaced by chemical substitutes such as BPS or BPF, that are structurally similar and not well studied compare to BPA. Here, we aimed to compare perinatal oral exposure to these bisphenols (BPs) at two doses (5 and 50 mg/kg body weight (BW)/day (d)) on gut barrier and immune system in female offspring mice at adulthood (Post Natal Day PND70). Methods Pregnant female mice were orally exposed to BPA, BPS or BPF at 5 or 50 μg/kg BW/d from 15th day of gravidity to weaning of pups at PostNatal Day (PND) 21. Gut barrier function and the humoral and cellular immune responses of adult offspring (PND70) were analysed at intestinal and systemic levels. Results In female offspring, perinatal oral BP exposure led to adverse effects on intestinal barrier and immune response that were dependant of the BP nature (A, S or F) and dose of exposure. Stronger impacts were observed with BPS at the dose of 5µg/kg BW/d on inflammatory markers in feces associated with an increase of anti-E. coli IgG, revealing a defect of gut barrier. BPA and BPF exposure induced prominent changes at low dose in offspring mice, in term of gut barrier functions and cellular immune responses, provoking an intestinal and systemic Th1/Th17 inflammation. Conclusion These findings provide, for the first time, a comparative study of long-time consequences of BPA, S and F perinatal exposure by oral route in offspring mice. This work warms that it is mandatory to consider immune markers and dose in risk assessment associated to new BPA’s alternatives. Keywords: Bisphenol A, Bisphenol S, Bisphenol F, Immune responses, Perinatal exposure, Intestine, Th1/Th17, immunoglobulin, cytokines

scholarly journals Dose-dependent acceleration in the delayed effects of neonatal oral exposure to low-dose 17α-ethynylestradiol on reproductive functions in female Sprague-Dawley rats

2015 ◽  
Vol 40 (6) ◽  
pp. 727-738 ◽  
Author(s):  
Mariko Shirota ◽  
Jun Kawashima ◽  
Tomohiro Nakamura ◽  
Junichi Kamiie ◽  
Kinji Shirota ◽  
...  
Keyword(s):  
Low Dose ◽  
Oral Exposure ◽  
Sprague Dawley ◽  
Delayed Effects ◽  
Sprague Dawley Rats ◽  
Dose Dependent

scholarly journals Oral exposure to low dose bisphenol A aggravates allergic airway inflammation in mice

2019 ◽  
Vol 6 ◽  
pp. 1253-1262 ◽  
Author(s):  
Rie Yanagisawa ◽  
Eiko Koike ◽  
Tin-Tin Win-Shwe ◽  
Hirohisa Takano
Keyword(s):  
Bisphenol A ◽  
Airway Inflammation ◽  
Low Dose ◽  
Allergic Airway Inflammation ◽  
Oral Exposure

scholarly journals Impact of Low Dose Oral Exposure to Bisphenol A (BPA) on the Neonatal Rat Hypothalamic and Hippocampal Transcriptome: A CLARITY-BPA Consortium Study

Endocrinology ◽  
2016 ◽  
Vol 157 (10) ◽  
pp. 3856-3872 ◽  
Author(s):  
Sheryl E. Arambula ◽  
Scott M. Belcher ◽  
Antonio Planchart ◽  
Stephen D. Turner ◽  
Heather B. Patisaul
Keyword(s):  
Bisphenol A ◽  
Low Dose ◽  
Neonatal Rat ◽  
Oral Exposure ◽  
Dose Oral

scholarly journals Impact of Low-Dose Oral Exposure to Bisphenol A (BPA) on Juvenile and Adult Rat Exploratory and Anxiety Behavior: A CLARITY-BPA Consortium Study

2015 ◽  
Vol 148 (2) ◽  
pp. 341-354 ◽  
Author(s):  
Meghan E. Rebuli ◽  
Luísa Camacho ◽  
Maria E. Adonay ◽  
David M. Reif ◽  
David L. Aylor ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Low Dose ◽  
Oral Exposure ◽  
Adult Rat ◽  
Dose Oral ◽  
Anxiety Behavior

scholarly journals Oral exposure to low-dose of nonylphenol impairs memory performance in Sprague-Dawley rats

2015 ◽  
Vol 40 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Shinichiro Kawaguchi ◽  
Rika Kuwahara ◽  
Yumi Kohara ◽  
Yutaro Uchida ◽  
Yushi Oku ◽  
...  
Keyword(s):  
Low Dose ◽  
Memory Performance ◽  
Oral Exposure ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

scholarly journals Bisphenol-A Dose-dependently Regulates The Development of Ovary and Uterus through Differential Expression of METTL3

2020 ◽  
Author(s):  
Zhe Zhang ◽  
Yuan Zhu ◽  
Zhifan Zhang ◽  
Daojuan Wang ◽  
Hongwei Wang ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Soybean Oil ◽  
Reproductive System ◽  
Low Dose ◽  
Polycystic Ovary ◽  
Female Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Blank Group ◽  
Rna Methylation

Abstract Background: Environmental endocrine disruptors, which have a profound impact on the reproductive system, can cause endocrine and reproductive disorders, such as polycystic ovary syndrome (PCOS). Bisphenol-A (BPA) is a common endocrine disruptor which can affect the function of the reproductive system under low-dose conditions. However, the mechanism by which this molecule disrupts normal reproduction is still unclear. In this study, we investigated the effects of BPA on the RNA methyltransferase METTL3 in adolescent female rats which may be a possible mode of action of BPA. Methods: 4-week-old Sprague-Dawley (SD) rats were intragastrically treated for 10 weeks, which were divided into blank group (n = 8), control group (soybean oil, n = 8), three BPA-treatment groups (0.5 mg/kg BPA + soybean oil, 5 mg/kg BPA + soybean oil, 50 mg/kg BPA + soybean oil, n = 8). Results: The results showed that low-dose BPA (0.5 mg/kg) increased the coefficient of uteri and ovaries, and promoted the growth of uteri in rats without causing hyperandrogenism and ovarian polycystic changes. Oral BPA disturbed the expression of CYP17A1, CYP11A1 and METTL3 in ovaries and effected the level of serum testosterone. Conclusions: Our results suggested that oral BPA might interfere uterine and ovarian morphology and the level of hormone with RNA methylation by disturbing the expression level of METTL3. RNA methylation will be a new way to explain the interference mechanism of BPA.

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