PMID: 

Invest Ophthalmol Vis Sci. 2009 May ;50(5):2398-406. Epub 2008 Dec 30. PMID: 19117929

Abstract Title: 

The flavonoid, eriodictyol, induces long-term protection in ARPE-19 cells through its effects on Nrf2 activation and phase 2 gene expression.

Abstract: 

PURPOSE: Eriodictyol, a flavonoid found in citrus fruits, is among the most potent compounds reported to protect human RPE cells from oxidative stress-induced cell death. The present study sought to determine whether eriodictyol-induced phase 2 protein expression further enhances the resistance of human ARPE-19 cells to oxidative stress.METHODS: The ability of eriodictyol to activate Nrf2 and to induce the phase 2 proteins heme-oxygenase (HO)-1 and NAD(P)H:quinone oxidoreductase (NQO)-1, and the cellular antioxidant glutathione (GSH) were analyzed. Cytoprotection assays in ARPE-19 cells that were overexpressing HO-1 or NQO-1 were performed, cell survival after short-term and long-term eriodictyol treatment was compared, and the mechanism of protection using a dominant negative Nrf2 and shRNA specific for HO-1 was tested.RESULTS: Eriodictyol induced the nuclear translocation of Nrf2, enhanced the expression of HO-1 and NQO-1, and increased the levels of intracellular glutathione. ARPE-19 cells that overexpress HO-1 or NQO-1 were more resistant to oxidative stress-induced cell death than control cells. Eriodictyol induced long-term protection significantly greater than its short-term protection. This effect was correlated temporally with the activation of Nrf2 and the induction of phase 2 enzymes and could be blocked with the use of a dominant negative Nrf2 and shRNA specific to HO-1.CONCLUSIONS: These findings indicate that the greatest benefit from eriodictyol may be its ability to regulate gene expression and enhance multiple cellular defenses to oxidative injury.

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PMID: 

Int J Mol Sci. 2019 Sep 6 ;20(18). Epub 2019 Sep 6. PMID: 31489946

Abstract Title: 

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

Abstract: 

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 (50μg/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 effectsof 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.

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PMID: 

Nutrients. 2019 Sep 6 ;11(9). Epub 2019 Sep 6. PMID: 31500194

Abstract Title: 

Bisphenol A Analogues in Food and Their Hormonal and Obesogenic Effects: A Review.

Abstract: 

Bisphenol A (BPA) is the most well-known compound from the bisphenol family. As BPA has recently come under pressure, it is being replaced by compounds very similar in structure, but data on the occurrence of these BPA analogues in food and human matrices are limited. The main objective of this work was to investigate human exposure to BPA and analogues and the associated health effects. We performed a literature review of the available research made in humans, in in vivo and in vitro tests. The findings support the idea that exposure to BPA analogues may have an impact on human health, especially in terms of obesity and other adverse health effects in children.

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PMID: 

Hum Exp Toxicol. 2019 Dec ;38(12):1344-1365. PMID: 31514588

Abstract Title: 

Prenatal BPA and its analogs BPB, BPF, and BPS exposure and reproductive axis function in the male offspring of Sprague Dawley rats.

Abstract: 

Research in the past has indicated associated long-term and low levels of exposure of bisphenol A (BPA) in early life and neuroendocrine disorders, such as obesity, precocious puberty, diabetes, and hypertension. BPA and its analogs bisphenol B (BPB), bisphenol F (BPF), and bisphenol S (BPS) have been reported to have similar or even more toxic effect as compared to BPA. Exposure of rats to BPA and its analogs BPB, BPF, and BPS resulted in decreased sperm production, testosterone secretion, and histological changes in the reproductive tissues of male rats. In the present study, BPA, BPB, BPF, and BPS were administered in drinking water at concentrations of (5, 25, and 50μg/L) from pregnancy day (PD) 1 to PD 21. Body weight (BW), hormonal concentrations, antioxidant enzymes, and histological changes were determined in the reproductive tissues. BPA and its analogs prenatal exposure to female rats induced significant statistical difference in the antioxidant enzymes,plasma testosterone, and estrogen concentrations in the male offspring when compared with the control. Histological parameters of both testis and epididymis revealed prominent changes in the reproductive tissues. The present study suggests that BPA and its analogs BPB, BPF, and BPS different concentrations led to marked alterations in the development of the male reproductive system.

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PMID: 

Toxicol Sci. 2019 Sep 10. Epub 2019 Sep 10. PMID: 31501865

Abstract Title: 

Gestational exposure to bisphenol A and bisphenol S leads to fetal skeletal muscle hypertrophy independent of sex.

Abstract: 

Gestational exposure to bisphenol A (BPA) can lead to offspring insulin resistance. However, despite the role that the skeletal muscle plays in glucose homeostasis, it remains unknown whether gestational exposure to BPA, or its analogue bisphenol S (BPS), impairs skeletal muscle development. We hypothesized that gestational exposure to BPA or BPS will impair fetal muscle development and lead to muscle-specific insulin resistance. To test this, pregnant sheep (n = 7-8/group) were exposed to BPA or BPS from gestational day (GD) 30 to 100. At GD120, fetal skeletal muscle was harvested to evaluate fiber size, fiber type, and gene and protein expression related to myogenesis, fiber size, fiber type, and inflammation. Fetal primary myoblasts were isolated to evaluate proliferation and differentiation. In fetal skeletal muscle, myofibers were larger in BPA and BPS groups in both females and males. BPA females had higher MYH1 (reflective of type-IIX fast glycolytic fibers), while BPS females had higher MYH2 and MYH7, and higher myogenic regulatory factors (Myf5, MyoG, MyoD, and MRF4) mRNA expression. No differences were observed in males. Myoblast proliferation was not altered in gestationally BPA- or BPS-exposed myoblasts, but upon differentiation, area and diameter of myotubes were larger independent of sex. Females had larger myofibers and myotubes than males in all treatment groups. In conclusion, gestational exposure to BPA or BPS does not result in insulin resistance in fetal myoblasts but leads to fetal fiber hypertrophy in skeletal muscle independent of sex and alters fiber type distribution in a sex-specific manner.

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PMID: 

J Cell Biochem. 2019 Sep ;120(9):14756-14770. Epub 2019 Apr 23. PMID: 31016762

Abstract Title: 

Eriodictyol alleviates lipopolysaccharide-triggered oxidative stress and synaptic dysfunctions in BV-2 microglial cells and mouse brain.

Abstract: 

Oxidative stress takes part in the development of the neurodegenerative disease. Eriodictyol, a flavonoid, commonly presents in citrus fruits, which was well-known for its various bioactivities. The purpose of this study was to investigate the neuroprotective effects of eriodictyol on lipopolysaccharide (LPS)-induced neuroinflammation, oxidative stress, synaptic dysfunctions, and the potential mechanisms involved. We found that eriodictyol explicitly restored LPS-triggered the decrease of cell viability and the mitochondrial potential as well as inflammation responses via mitogen-activated protein kinases (MAPKs) and nuclear factorκB (NF-κB) pathways regulated by reactive oxygen species (ROS). Besides, eriodictyol alleviated LPS-induced oxidative stress via NF-E2-Related factor2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) pathway in vivo and in vitro. Furthermore, eriodictyol reduced LPS-elicited synaptic dysfunctionsvia increasing the expression of silent information regulator 1 (Sirt1). Overall, eriodictyol protects LPS-triggered oxidative stress, neuroinflammation, and synaptic dysfunctions partially through MAPKs, NF-κB mediated by ROS, Sirt1, and Nrf2/Keap1 signal pathways, which further supports that eriodictyol is a potentially nutritional preventive strategy for oxidative stress-related neurodegenerative diseases.

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PMID: 

Neurochem Int. 2012 Jul ;61(2):251-7. Epub 2012 May 17. PMID: 22609376

Abstract Title: 

Eriodictyol protects against H(2)O(2)-induced neuron-like PC12 cell death through activation of Nrf2/ARE signaling pathway.

Abstract: 

Eriodictyol, a flavonoid isolated from the Chinese herb Dracocephalum rupestre has long been established as an antioxidant. The present study was designed to explore the protective effects of eriodictyol against hydrogen peroxide (H(2)O(2))-induced neurotoxicity with cultured rat pheochromocytoma cells (PC12 cells) and the possible mechanisms involved. For this purpose, differentiated PC12 cells were cultured and exposed to 200μM H(2)O(2) in the absence or presence of eriodictyol (20, 40 and 80 μM). In addition, the potential contribution of the Nrf2/ARE neuroprotective pathway in eriodictyol-mediated protection against H(2)O(2)-induced neurotoxicity was also investigated. The results showed that H(2)O(2)-induced cell death can be inhibited in the presence of eriodictyol as measured by assays for MTT and apoptosis. Further study revealed that eriodictyol induced the nuclear translocation of Nrf2, enhanced the expression of heme oxygenase (HO-1) and γ-glutamylcysteine synthetase (γ-GCS), and increased the levelsof intracellular glutathione. Treatment of PC12 cells with Nrf2 small interference RNA abolished eriodictyol-induced HO-1 and γ-GCS expression and its protective effects. In conclusion, these results suggest that eriodictyol upregulates HO-1 and γ-GCS expression through the activation of Nrf2/AREpathway and protects PC12 cells against H(2)O(2)-induced oxidative stress.

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PMID: 

J Agric Food Chem. 2012 Aug 8 ;60(31):7652-8. Epub 2012 Jul 31. PMID: 22809065

Abstract Title: 

Effect of eriodictyol on glucose uptake and insulin resistance in vitro.

Abstract: 

Eriodictyol [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-2,3-dihydrochromen-4-one] is a flavonoid with anti-inflammatory and antioxidant activities. Because inflammation and oxidative stress play critical roles in the pathogenesis of diabetes mellitus, the present study was designed to explore whether eriodictyol has therapeutic potential for the treatment of type 2 diabetes. The results show that eriodictyol increased insulin-stimulated glucose uptake in both human hepatocellular liver carcinoma cells (HepG2) and differentiated 3T3-L1 adipocytes under high-glucose conditions. Eriodictyol also up-regulated the mRNA expression of peroxisome proliferator-activated receptorγ2 (PPARγ2) and adipocyte-specific fatty acid-binding protein (aP2) as well as the protein levels of PPARγ2 in differentiated 3T3-L1 adipocytes. Furthermore, it reactivated Akt in HepG2 cells with high-glucose-induced insulin resistance. This response was strongly inhibited by pretreatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, indicating that eriodictyol increased Akt phosphorylation by activating the PI3K/Akt pathway. These results imply that eriodictyol can increase glucose uptake and improve insulin resistance, suggesting that it may possess antidiabetic properties.

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PMID: 

J Biol Chem. 2011 Jan 21 ;286(3):2057-66. Epub 2010 Nov 22. PMID: 21098035

Abstract Title: 

Eriodictyol inhibits RSK2-ATF1 signaling and suppresses EGF-induced neoplastic cell transformation.

Abstract: 

RSK2 is a widely expressed serine/threonine kinase, and its activation enhances cell proliferation. Here, we report that ATF1 is a novel substrate of RSK2 and that RSK2-ATF1 signaling plays an important role in EGF-induced neoplastic cell transformation. RSK2 phosphorylated ATF1 at Ser-63 and enhanced ATF1 transcriptional activity. Docking experiments using the crystal structure of the RSK2 N-terminal kinase domain combined with in vitro pulldown assays demonstrated that eriodictyol, a flavanone found in fruits, bound with the N-terminal kinase domain of RSK2 to inhibit RSK2 N-terminal kinase activity. In cells, eriodictyol inhibited phosphorylation of ATF1 but had no effect on the phosphorylation of RSK, MEK1/2, ERK1/2, p38 or JNKs, indicating that eriodictyol specifically suppresses RSK2 signaling. Furthermore, eriodictyol inhibited RSK2-mediated ATF1 transactivation and tumor promoter-induced transformation of JB6 Cl41 cells. Eriodictyol or knockdown of RSK2 or ATF1 also suppressed Ras-mediated focus formation. Overall, these results indicate that RSK2-ATF1 signaling plays an important role in neoplastic cell transformation and that eriodictyol is a novel natural compound for suppressing RSK2 kinase activity.

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PMID: 

Health Phys. 2013 Dec ;105(6):561-75. PMID: 24162060

Abstract Title: 

Wi-Fi and health: review of current status of research.

Abstract: 

This review summarizes the current state of research on possible health effects of Wi-Fi (a commercial name for IEEE 802.11-compliant wireless networking). In response to public concerns about health effects of Wi-Fi and wireless networks and calls by government agencies for research on possible health and safety issues with the technology, a considerable amount of technology-specific research has been completed. A series of high quality engineering studies have provided a good, but not complete, understanding of the levels of radiofrequency (RF) exposure to individuals from Wi-Fi. The limited number of technology-specific bioeffects studies done to date are very mixed in terms of quality and outcome. Unequivocally, the RF exposures from Wi-Fi and wireless networks are far below U.S. and international exposure limits for RF energy. While several studies report biological effects due to Wi-Fi-type exposures, technical limitations prevent drawing conclusions from them about possible health risks of the technology. The review concludes with suggestions for future research on the topic.

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