scholarly journals Effects of Bisphenol A on Incidence and Severity of Cardiac Lesions in the NCTR-Sprague-Dawley Rat: A CLARITY-BPA Study

2017 ◽  
Author(s):  
Robin Gear ◽  
Jessica A. Kendziorski ◽  
Scott M. Belcher

AbstractThe goal of this study was to determine whether bisphenol A (BPA) had adverse effects indicative of cardiac toxicity. As part of the “Consortium Linking Academic and Regulatory Insights on BPA Toxicity” (CLARITY-BPA), study dams and offspring were exposed by daily gavage to five doses of BPA ranging from 2.5 to 25000 μg/kg/day, 0.05 or 0.5 μg/kg/day 17α-ethinyl-estradiol (EE) or 0.3% carboxymethylcellulose vehicle. Exposure-related effects were analyzed in isolated hearts by quantitative morphometry and histopathology. No dose-related changes in body weight were detected. Across all exposure groups including vehicle controls, body weight of continuously dosed males was reduced compared to males dosed only until PND21. Heart weight was increased only in females exposed to EE, and consistent alterations in LV wall thickness were not observed. Exposure-related changes in collagen accumulation were minor and limited to highest EE exposure groups with increased collagen accumulation in PND21 males. Decreased collagen was observed in hearts of BPA or EE exposed females at PND90 and PND180. In BPA or EE treated females cardiomyopathy incidence and severity was significantly increased compared to control females at PND21 with myocardial degeneration observed in both males and females at PND21 and PND90.

Endocrinology ◽  
2019 ◽  
Vol 160 (8) ◽  
pp. 1771-1785 ◽  
Author(s):  
Ruby Bansal ◽  
R Thomas Zoeller

Abstract The CLARITY-BPA experiment, a large collaboration between the National Institute of Environmental Health Sciences, the National Toxicology Program, and the US Food and Drug Administration, is designed to test the effects of bisphenol A (BPA) on a variety of endocrine systems and end points. The specific aim of this subproject was to test the effect of BPA exposure on thyroid functions and thyroid hormone action in the developing brain. Timed-pregnant National Center for Toxicological Research Sprague-Dawley rats (strain code 23) were dosed by gavage with vehicle control (0.3% carboxymethylcellulose) or one of five doses of BPA [2.5, 25, 250, 2500, or 25,000 µg/kg body weight (bw) per day] or ethinyl estradiol (EE) at 0.05 or 0.50 µg/kg bw/d (n = 8 for each group) beginning on gestational day 6. Beginning on postnatal day (PND) 1 (day of birth is PND 0), the pups were directly gavaged with the same dose of vehicle, BPA, or EE. We also obtained a group of animals treated with 3 ppm propylthiouracil in the drinking water and an equal number of concordant controls. Neither BPA nor EE affected serum thyroid hormones or thyroid hormone‒sensitive end points in the developing brain at PND 15. In contrast, propylthiouracil (PTU) reduced serum T4 to the expected degree (80% reduction) and elevated serum TSH. Few effects of PTU were observed in the male brain and none in the female brain. As a result, it is difficult to interpret the negative effects of BPA on the thyroid in this rat strain because the thyroid system appears to respond differently from that of other rat strains.


2021 ◽  
Vol 7 (2) ◽  
pp. 62-68
Author(s):  
Andreas Arie Setiawan ◽  
Fairuz Azmila Purnomo ◽  
Vega Karlowee ◽  
Noor Wijayahadi

ABSTRACTBackground: Obesity is a disorder or disease characterized by the accumulation of excess fat in the body due to an imbalance in energy intake that is used for a long time. Accumulation of fat can reduce adiponectin, causing cardiac hypertrophy, endothelial vasodilation, and other cardiovascular diseases. Black garlic have high antioxidants in the form of S-Allylcysteine(SAC) which functions to increase adiponectin. Objective: To determine the effect of Black garlic on the histopathological picture of the heart and aorta of obese rats. Methods: This study was an experimental study with a randomized post-test only design with control group design with 5 groups of male white rats Sprague Dawley (Rattus novergicus) fed High Fat Fructose. Diet (HFFD) enriched with 1.25% cholesterol and 0.5% cholic acid for 8 weeks and was given black garlic intervention at doses of 450 mg / 200BW, 900mg / 200BW and 1350mg200 / BW for 4 weeks. Results: Giving black garlic significantly reduced body weight of rats (p = 0.001), and the results did not significantly reduce heart weight (p = 0.147), aortic weight (p = 0.061), histopathological changes in heart wall thickness (p = 0.423) and aortic wall thickness (p = 0.802). The effective doses of black garlic in this study were 450 mg / 200 grams BW, 900 mg / 200 grams rat BW and 1350 mg / 200 grams BW of rats. The optimal dose is 900 mg / 200 grams BW. Conclusion: Black garlic gave a significant reduction in body weight of rats and no significant reduction in heart weight, aortic weight, cardiac and aortic histopathological features. 


1983 ◽  
Vol 244 (3) ◽  
pp. H444-H448 ◽  
Author(s):  
D. L. Crandall ◽  
F. M. Lai ◽  
F. J. Huggins ◽  
T. K. Tanikella ◽  
P. Cervoni

The effect of a 21-day program of caloric restriction on cardiac reactivity and beta-adrenoceptor number was investigated in male Sprague-Dawley rats. Rats on the restricted diet (Restricted) exhibited significant decreases in body weight, epididymal fat pad, and retroperitoneal fat pad weight as well as the percent of body fat represented by these adipose tissue depots when compared with rats fed ad libitum (Fed). Fed rats exhibited significantly increased total heart weight and total heart protein, but the percent cardiac protein and ratio of heart weight to body weight were similar in Fed and Restricted rats. Isolated atria from Fed and Restricted rats developed similar chronotropic and inotropic responses over a range of isoproterenol concentrations. Although total beta-adrenoceptor number (fmol/heart) was greater in Fed rats, the concentration of beta-adrenoceptors (fmol/mg protein) was remarkably similar regardless of the dietary regimen. Therefore, despite significant decreases in body weight, body fat, and heart weight, the myocardium of Restricted rats maintained the capability of responding to isoproterenol as that of Fed rats, the mechanism of which is at least partially mediated through maintenance of beta-adrenoceptor concentration.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sara B. Fournier ◽  
Vincent Lam ◽  
Michael J. Goedken ◽  
Laura Fabris ◽  
Phoebe A. Stapleton

AbstractMaternal exposure to environmental contaminants during pregnancy can profoundly influence the risk of developing cardiovascular disease in adult offspring. Our previous studies have demonstrated impaired cardiovascular health, microvascular reactivity, and cardiac function in fetal and young adult progeny after maternal inhalation of nano-sized titanium dioxide (nano-TiO2) aerosols during gestation. The present study was designed to evaluate the development of cardiovascular and metabolic diseases later in adulthood. Pregnant Sprague–Dawley rats were exposed to nano-TiO2 aerosols (~ 10 mg/m3, 134 nm median diameter) for 4 h per day, 5 days per week, beginning on gestational day (GD) 4 and ending on GD 19. Progeny were delivered in-house. Body weight was recorded weekly after birth. After 47 weeks, the body weight of exposed progeny was 9.4% greater compared with controls. Heart weight, mean arterial pressure, and plasma biomarkers of inflammation, dyslipidemia, and glycemic control were recorded at 3, 9 and 12 months of age, with no significant adaptations. While no clinical risk factors (i.e., hypertension, dyslipidemia, or systemic inflammation) emerged pertaining to the development of cardiovascular disease, we identified impaired endothelium-dependent and -independent arteriolar dysfunction and cardiac morphological alterations consistent with myocardial inflammation, degeneration, and necrosis in exposed progeny at 12 months. In conclusion, maternal inhalation of nano-TiO2 aerosols during gestation may promote the development of coronary disease in adult offspring.


2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Deborah M Eaton ◽  
Remus Berretta ◽  
Jacqueline E Lynch ◽  
Joshua G Travers ◽  
Kathleen C Woulfe ◽  
...  

Rationale: Heart Failure with preserved Ejection Fraction (HFpEF) accounts for approximately 50% of all HF diagnoses with no FDA approved therapies. HFpEF is more prevalent in females versus males, but the mechanisms driving the development of HFpEF as a sex-based disorder are not well understood. We have recently shown that slow progressive pressure overload (PO) in male felines induces a HFpEF phenotype but have not investigated the differences in response to the same physiological stress in females. Hypothesis: Females will develop a phenotype that is distinct from males in response to PO. Methods and Results: Male (m) and female (f) domestic short felines (age 2mo) underwent either a sham procedure (m: n=7; f: n=7) or aortic constriction (m: n=11; f: n=10) using a customized pre-shaped band. At baseline (prior to surgery), there was no difference in body weight between groups and echocardiography revealed no significant difference in the ratio of left atrium to aortic root (LA/Ao), LA ejection fraction (LA EF), left ventricle (LV) ejection fraction, LV wall-thickness, and E/A ratio. At 4mo post-surgery, both males and females developed cardiac dysfunction. Females gained significantly less weight than males throughout the study. Despite the size difference, both sexes developed comparable LV wall thickness and changes in E/A ratio vs. sham groups. There was no change in LV EF. Furthermore, there was a decrease in LA EF and increased LA/Ao, indicating LA dysfunction and enlargement. Invasive hemodynamics at 4mo post-surgery showed no differences between sexes for the systolic pressure gradient generated by the aortic banding. Banded males had a significantly higher LV end-diastolic pressure vs. banded females, but there was a trend towards prolongation of tau and lower dp/dt min in banded females, reflective of worse active relaxation. Both sexes had comparable dP/dt max . There were no differences between banded males and females in heart weight to body weight or cardiomyocyte cross-sectional area. Conclusion: Despite similar pressure gradients as a result of PO and the development of similar cardiac hypertrophy between sexes and a higher LVEDP in males, females had a trend towards worse relaxation. Other causes of HFpEF may have sex-based differences.


1992 ◽  
Vol 73 (2) ◽  
pp. 446-451 ◽  
Author(s):  
H. S. Sekhon ◽  
W. M. Thurlbeck

Postpneumonectomy compensatory lung response and normal lung growth in the early postnatal period were studied in male and female rats. Four-week-old litter-matched male and female Sprague-Dawley rats were subjected to left pneumonectomy or sham operation and followed for 3 wk. In both sexes after pneumonectomy, lung weight (WL), lung volume (VL), alveolar surface area (Sw), total alveolar number (N(at)), and the amount of DNA and protein increased significantly. In both males and females, WL, VL, and Sw matched those of both lungs of the sham-operated group, but N(at) and the amount of DNA and protein did not. Female pneumonectomy and sham-operated rats were smaller in body weight than males. Absolute WL, VL, Sw, N(at), and the amount of DNA and protein were significantly lower, but specific parameters (per unit body weight) were significantly greater in females than in males. After pneumonectomy, the postcaval lobe increased most in volume (70 and 73% in males and females, respectively). Mean linear intercept and mean chord length of alveoli increased, and the number of alveoli per unit volume decreased more in the postcaval and middle lobes than in upper and lower lobes in both sexes. Postpneumonectomy, loss of elastic lung recoil was observed in females. We conclude that, in certain aspects (WL, VL), compensatory growth matched both lungs of controls, but in others (biochemical, morphometric) it did not. There was evidence of alveolar multiplication, but the dominant effect was enlargement of air spaces.(ABSTRACT TRUNCATED AT 250 WORDS)


2018 ◽  
Vol 3 (1) ◽  
pp. 149-154
Author(s):  
Kathy Zurbrigg ◽  
Tony van Dreumel ◽  
Max F Rothschild ◽  
David Alves ◽  
Robert M Friendship ◽  
...  

Abstract In-transit losses of market hogs represent a small proportion of all market-weight pigs shipped in a year. This suggests that individual pig factors may be a significant cause of in-transit losses along with more traditionally considered environmental and transport factors. An investigation was performed to determine whether cardiac pathology and heart weights were associated with pigs that did or did not die during transport to an abattoir. The hearts from 70 pigs that died in-transit to one Ontario abattoir and 388 pigs that arrived alive were collected and examined. Hearts from pigs that died during transport demonstrated greater frequencies of cardiac lesions (P < 0.05). These included hypertrophy of ventricle walls (Left: 97% vs. 64%; Right: 86% vs. 57%), dilation of ventricle chambers (Left: 79% vs. 0.5%; Right: 100% vs. 5%), and dilation of the pulmonary artery and aorta (59% vs. 1.5%). Total heart weight to body weight ratios were increased (3.6 vs. 3.3 g/kg) and left ventricle plus septum weight over right ventricle weight ratio was decreased in pigs that died during transport over non–in-transit loss pigs (2.5 vs. 2.8; P < 0.05). This may indicate reduced cardiac function in hogs that died during transport. Pigs with reduced cardiac function would have exercise intolerance and be more susceptible to death during transport due to the increased cardiac workload required during sorting, loading, and transport of the pigs to the abattoir. Further research to quantify cardiac function in pigs with cardiac lesions or abnormal heart weight ratios is warranted.


2021 ◽  
Vol 12 ◽  
Author(s):  
Syed Mohammed Basheeruddin Asdaq ◽  
Obulesu Challa ◽  
Abdulhakeem S. Alamri ◽  
Walaa F. Alsanie ◽  
Majid Alhomrani ◽  
...  

Garlic oil and its primary component, diallyl disulphide (DADS), were tested in rats with isoprenaline (ISO) induced myocardial infarction for cardioprotective benefits when combined with carvedilol. Garlic oil (GO) was administered to rats (Sprague-dawley strain) at two doses of 50 and 100 mg/kg body weight, whereas DADS was given in two doses of 4.47 and 8.94 mg/kg, respectively. The animals were given oral doses of garlic oil and DADS on alternate days for 3 weeks, either alone or in combination with carvedilol (2 mg/kg). Cardiac injury was done by administering two doses of isoprenaline (150 mg/kg, sc) to all treated groups except the first, which served as a control. Biomarkers of cardiac injury and histological investigations were studied for their potential in reducing ISO-induced myocardial damage. Animals pretreated with GO, DADS, and carvedilol had significantly (p < 0.01) lowered heart weight and heart to body weight ratio. In rats treated with carvedilol plus high dosages of garlic oil (100 mg/kg, p.o) and DADS (8.94 mg/kg, p.o) compared to the ISO control and carvedilol group, the activities of SOD and Catalase were enhanced in cardiac tissue homogenate. When compared to ISO control and carvedilol group, the activities of LDH and CK-MB were elevated in heart tissue homogenate with a simultaneous reduction in their serum levels in animals treated with a combination of carvedilol with high doses of garlic oil (100 mg/kg, p.o) and DADS (8.94 mg/kg, p.o). Overall, combining garlic oil or DADS with carvedilol improved the cardioprotective effect of carvedilol and protected rats from ISO-induced myocardial infarction. However, more research is needed to establish the mechanism of garlic oil and DADS interaction with carvedilol.


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