scholarly journals Maternal Resveratrol Therapy Protects Male Rat Offspring against Programmed Hypertension Induced by TCDD and Dexamethasone Exposures: Is It Relevant to Aryl Hydrocarbon Receptor?

2018 ◽  
Vol 19 (8) ◽  
pp. 2459 ◽  
Author(s):  
Chien-Ning Hsu ◽  
Yu-Ju Lin ◽  
Pei-Chen Lu ◽  
You-Lin Tain
Keyword(s):  
Oxidative Stress ◽  
Aryl Hydrocarbon Receptor ◽  
Signaling Pathway ◽  
Renin Angiotensin System ◽  
Male Rat ◽  
Beneficial Effects ◽  
Rat Offspring ◽  
Aryl Hydrocarbon ◽  
Induced Hypertension ◽  
Pregnancy And Lactation

Hypertension can originate from early-life adverse environmental in utero exposure to dexamethasone (DEX) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Since DEX and TCDD are related to the aryl hydrocarbon receptor (AHR) signaling pathway, we examined whether resveratrol, an AHR modulator and antioxidant, could prevent programmed hypertension via regulating AHR signaling and oxidative stress. Groups of four-month-old male rat offspring were studied (n = 7–8 per group): control, DEX (0.1 mg/kg i.p. from a gestational age of 16 to 22 days), TCDD (200 ng/kg in four once-weekly oral doses), DEX + TCDD, and DEX + TCDD + R (resveratrol 0.05% in drinking water throughout pregnancy and lactation). Maternal TCDD exposure aggravated prenatal DEX-induced hypertension in adult male offspring, which maternal resveratrol therapy prevented. Maternal TCDD exposure aggravated DEX-induced oxidative damage in offspring kidneys, which was prevented by resveratrol therapy. Maternal resveratrol therapy decreased asymmetric and symmetric dimethylarginine (ADMA and SDMA) levels, thereby preventing combined DEX and TCDD exposure-induced programmed hypertension. Increases in renal Ahrr and Cyp1a1 expression induced by DEX + TCDD exposure were restored by resveratrol therapy. The beneficial effects of resveratrol on DEX + TCDD-induced hypertension relate to reduced renal mRNA expression of Ren, Ace, and Agtr1a expression. Thus, the beneficial effects of resveratrol on DEX + TCDD-induced hypertension include reduction of oxidative stress, restoration of nitric oxide (NO) bioavailability, blockade of the renin–angiotensin system (RAS), and antagonizing AHR signaling pathway.

scholarly journals Maternal Exposure to Bisphenol A Combined with High-Fat Diet-Induced Programmed Hypertension in Adult Male Rat Offspring: Effects of Resveratrol

2019 ◽  
Vol 20 (18) ◽  
pp. 4382 ◽  
Author(s):  
Chien-Ning Hsu ◽  
Yu-Ju Lin ◽  
You-Lin Tain
Keyword(s):  
Oxidative Stress ◽  
Bisphenol A ◽  
Signaling Pathway ◽  
Adult Male ◽  
Endocrine Disrupting Chemicals ◽  
Maternal Exposure ◽  
Male Rat ◽  
High Fat ◽  
Rat Offspring ◽  
No Bioavailability

Maternal exposure to endocrine disrupting chemicals (EDCs) and a high-fat intake may induce the developmental programming of hypertension in adult offspring. Bisphenol A (BPA) is one of the most commonly environmental EDCs. As the nitric oxide (NO) and aryl hydrocarbon receptor (AHR) signaling pathways both contribute to the pathogenesis of hypertension, we evaluated whether resveratrol, an antioxidant and an AHR antagonist, can prevent hypertension programmed by a maternal BPA and HF diet. Sixteen-week-old male rat offspring were assigned to six groups (n = 8 per group): Control, HF (D12331, Research Diets), BPA (50 μg/kg/day), HF + BPA, BPA + R (resveratrol 50mg/L in drinking water throughout pregnancy and lactation), and HF + BPA + R. Maternal BPA exposure exacerbated hypertension programmed by HF consumption in adult male offspring, which was protected by maternal resveratrol therapy. The BPA and HF diet synergistically induced oxidative stress in offspring kidneys, which resveratrol treatment prevented. We observed that HF + BPA-induced programmed hypertension was associated with a decreased NO bioavailability, increased oxidative stress, and an activated AHR signaling pathway. The beneficial effects of resveratrol are relevant to restoring NO bioavailability, reducing oxidative stress, and antagonizing the AHR signaling pathway. Our results cast a new light on resveratrol as a reprogramming strategy to protect against hypertension programmed by combined BPA and HF exposure, but this strategy has yet to be translated into clinical applications.

scholarly journals A comprehensive contribution of genes for aryl hydrocarbon receptor signaling pathway to hypertension susceptibility

2017 ◽  
Vol 27 (2) ◽  
pp. 57-69 ◽  
Author(s):  
Alexey V. Polonikov ◽  
Olga Yu. Bushueva ◽  
Irina V. Bulgakova ◽  
Maxim B. Freidin ◽  
Mikhail I. Churnosov ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Signaling Pathway ◽  
Receptor Signaling ◽  
Aryl Hydrocarbon ◽  
Receptor Signaling Pathway

scholarly journals Hepatic Transcriptome Reveals That Fructose Downregulated Xenobiotics Metabolizing Enzymes Through Aryl Hydrocarbon Receptor Signaling Suppression in C57BL/6 N Mice (P15-011-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jeong Hoon Pan ◽  
Jingsi Tang ◽  
Kaleigh Beane ◽  
Mersady Redding ◽  
Jiangchao Zhao ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Signaling Pathway ◽  
Bioinformatic Analysis ◽  
University Of Arkansas ◽  
Rt Pcr ◽  
Aryl Hydrocarbon ◽  
Fructose Intake ◽  
Upstream Regulator ◽  
Mice Liver ◽  
The University

Abstract Objectives For decades, fructose intake has been recognized as an environmental risk for metabolic syndromes and diseases. Thus, we comprehensively examined the effects of fructose intake on mice liver transcriptomes. Methods Fructose supplemented water (34%; wt/vol) was fed to both male and female C57BL/6 N mice at their free will for six weeks, followed by hepatic transcriptomics analysis. Based on our criteria, differentially expressed genes (DEGs) were selected and subjected to further computational analyses to predict key pathways and upstream regulator(s). Subsequently, predicted genes and pathways from the transcriptomics dataset were validated via quantitative RT-PCR analyses. Results As results, we identified 89 down-regulated and 88 up-regulated mRNAs in fructose-fed mice livers. These DEGs were subjected to bioinformatic analysis tools in which DEGs were mainly enriched in xenobiotic metabolic processes; further, in the Ingenuity Pathway Analysis software, it was suggested that the aryl hydrocarbon receptor (AhR) is an upstream regulator governing overall changes while fructose suppresses the AhR signaling pathway. In our quantitative RT-PCR validation, we confirmed that fructose suppressed AhR signaling through modulating expressions of transcription factor (arnt) and upstream regulators (ncor2, and rb1). Conclusions Altogether, we demonstrated that ad libitum fructose intake suppresses the canonical AhR signaling pathway in C57BL/6 N mice liver. Based on our current observations, further studies are warranted, especially with regard to the effects of co-exposure to fructose on 1) other types of carcinogens and 2) inflammation inducing agents (or even diets such as a high-fat diet), to find implications of fructose induced-AhR suppression. Funding Sources This work was supported by the University of Arkansas, VPRED Start-up fund and Dale Bumpers College of Agricultural, Food and Life Sciences. Support has been also provided in part by the Arkansas Biosciences Institute, a partnership of scientists from Arkansas Children's Hospital, Arkansas State University, the University of Arkansas-Division of Agriculture, the University of Arkansas, Fayetteville, and the University of Arkansas for Medical Sciences. The Arkansas Biosciences Institute is the major research component of the Arkansas Tobacco Settlement Proceeds Act of 2000. Supporting Tables, Images and/or Graphs

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