Quercetin protects the vascular endothelium against iron overload damages via ROS/ADMA/DDAHⅡ/eNOS/NO pathway

Chen, Xuepiao; Li, Hongwei; Wang, Zhiqing; Zhou, Qing; Chen, Shuping; Yang, Bin; Yin, Dong; He, Huan; He, Ming

doi:10.1016/j.ejphar.2019.172885

Cited by 46 publications

(29 citation statements)

References 57 publications

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“…Iron dysfunction also contributes to mitochondria defects, which is decisive for β cells in the progress of type 2 diabetes [ 29 ]. As a natural iron chelator, quercetin is reported to prevent liver injury in iron overload mice [ 30 ] (Zhang et al, 2011) and also demonstrated to effectively reduce iron deposition in endothelial cells [ 31 ]. In our study, T2DM mice exhibited increased iron concentration both in serum and pancreas tissues, and ferritin seemed to deposit particularly on or near islets manifested by immunohistochemical observation, showing a great iron overload in islets of pancreatic tissues and these iron depositions were attenuated by quercetin treatment.…”

Section: Resultsmentioning

confidence: 99%

Quercetin Alleviates Ferroptosis of Pancreatic β Cells in Type 2 Diabetes

et al. 2020

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(1) Background: Pancreatic iron deposition has been found in the progression of type 2 diabetes (T2DM); however, whether ferroptosis contributes to the dysfunction of pancreatic β cells (PBC) remains enigmatic. Moreover, the potential protective effect of quercetin is also elusive; (2) Methods: T2DM mice model was established by multiple low dose streptozocin (STZ) injection, after which quercetin was intervened for 4 months; (3) Results: Substantially normalized glucose tolerance, diabetic symptoms, homeostasis model assessment for insulin resistance (HOMA-IR), and homeostasis model assessment for β cell (HOMA-β) index in comparison with the findings of T2DM control. Distorted pancreatic islets and especially shrunken mitochondria with cristae loss in PBC were observed in T2DM mice, which was ameliorated by quercetin. Meanwhile, quercetin lowered the iron level particularly in the islet in T2DM mice. In spite of compensatory xCT up-regulation, T2DM molding depleted glutathione (GSH), down-regulated glutathione peroxidase 4 (GPX4), and induced oxidative stress in pancreatic tissue, which was abolished partially by quercetin. More importantly, insulin secretion was worsened by ferroptosis-inducing erastin or RAS-selective lethal compounds 3 (RSL-3). Quercetin, ferroptosis inhibitor ferrostatin-1 and iron-chelating deferoxamine, rescued cell viability when cells were challenged with high-glucose; (4) Conclusions: Our findings identify that ferroptosis contributes to the PBC loss and dysfunction. Quercetin exerts beneficial effects on T2DM potentially by inhibiting pancreatic iron deposition and PBC ferroptosis, highlighting promising control strategies of T2DM by quercetin.

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Section: Resultsmentioning

confidence: 99%

Quercetin Alleviates Ferroptosis of Pancreatic β Cells in Type 2 Diabetes

et al. 2020

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“…In addition, single-cell transcriptome analysis has shown that ferroptosis of granulocytes may be responsible for the high proportion of granulocytes in colorectal cancer liver metastasis samples, showing that the tumor microenvironment is another crucial target in oncotherapy that is closely connected to ferroptosis [81]. Clinical anticarcinogens containing ferroptosis inducers have widespread applications in iron-rich tumor tissues, including hepatoma and pancreatic carcinoma [16,31,54]. Combination therapy with piperlongumine, cotylenin A, and SAS has shown effectiveness as a treatment for pancreatic carcinoma via induction of ferroptosis [82].…”

Section: The Links Between Ferroptosis and Disordersmentioning

confidence: 99%

“…As mentioned above, ROS, which originate from iron overload, GSH depletion, and ETC-ROS, trigger ROS-induced ROS release (RIRR) and consequently very high ROS accumulation, a phenomenon that is also observed in iron-treated endothelial cells [ 41 , 53 , 54 ]. On account of the reverse effect of the proapoptosis protein BID inhibitor BI6c9 in increasing ROS and mitochondrial fragmentation as well as decreasing MMP and ATP levels in erastin-treated neuronal HT-22 cells, Neitemeier et al substantiated that excess ROS promoted BID transactivation to let BID translocate into mitochondria, ultimately leading to the collapse of MMP, the sustained opening of mPTPs, and mitochondrial damage [ 55 ].…”

Section: Crosstalk Related To Ferroptosismentioning

confidence: 99%

Revisiting Tumors and the Cardiovascular System: Mechanistic Intersections and Divergences in Ferroptosis

Wang

Xiang

Zhang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Ferroptosis was recently identified as an iron-dependent regulatory necrosis process mediated by polyunsaturated fatty acid (PUFA) peroxidation. The pivotal events related to oxidative stress in ferroptosis include direct or indirect glutathione peroxidase 4 (GPX4) inhibition, ferrous iron overload, and lipid peroxidation. The links between ferroptosis and multiple pathological processes including tumor and cardiovascular system disease have become increasingly apparent, and the mechanisms and compounds involved in ferroptosis, such as reduction of coenzyme Q10 (ubiquinone/CoQ10), are gradually emerging. Current reports have revealed crossroads between ferroptosis and other multiple responses. This overview of the current research illuminates the mechanisms involving ferroptosis-related compounds and emphasizes the crosstalk between ferroptosis and other responses, including mitochondrial damage, endoplasmic reticulum stress (ER stress), autophagy, and the release of damage-associated molecular patterns (DAMPs), to reveal the intersections of regulatory mechanisms. This review also outlines the discovery, characterization, and pathological relevance of ferroptosis and notes controversial elements in ferroptosis-related mechanisms, such as nuclear factor E2-related factor 2 (Nrf2), sequestosome 1 (p62/SQSTM1), and heat shock protein family A member 5 (HSPA5). We hope our inferences will supply a partial reference for disorder prevention and treatment.

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“…Корвітин зменшує продукцію вільних радикалів, стабілізує метаболізм системи оксиду азоту (Гапонова та ін., 2015). Антиоксиданти природного по-ходження, до яких відноситься корвітин виступають у якості пасток для АФК і сприяють активації антиоксидантів, особливо каталази і супероксиддисмутази (Мойбенко і Пархоменко, 2015, Monika et al, 2015, Oyagbemi at al., 2018, Chen at al., 2020. На це вказує позитивна динаміка змін проокисно-антиоксидантної системи в тканинах серця, нирок і печінки під впивом комбінованої терапії.…”

Section: таблицяunclassified

Зміни Проокисно-Антиоксидантної Системи У Щурів Серії SHR При Лікуванні Гіпотензивними Препаратами (Раміприлом І Кандесартаном) В Комбінації З Корвітином

Marushchak

Rohovyi²,

Савчук

2020

USMYJ

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Nowadays arterial hypertension (AH) is the most popular cardiovascular disease, which is the most common cause of disability in the population due to high risk of developing complications, such as heart failure, coronary artery disease, stroke. The nature of the morphological manifestations of hypertensive disease depends on the duration and severity, but hypertension triggers a cascade of pathological changes in the lung disease and is accompanied by disruption of the structure of organs that are the most sensitive to fluctuations of blood pressure (brain, heart, kidneys). Continuing the search for new drugs that not only lower blood pressure, but have polytropic effects. In the first place is cardioprotection, which is based on the principles of continuous monitoring of myocardial oxygenation and metabolism. Recently the attention of researchers attract bioflavonoids, such as corvitin, which showed antioxidant, prediabetics, anti-inflammatory properties. The question of influence corvitin in combination therapy with antihypertensive drugs in the treatment of hypertension has been insufficiently studied, that determines the relevance and purpose of our study. Materials and methods. The study was conducted spontaneously hypertensed of rats SHR series. Animals affected into 4 groups of observation. Experienced animal groups series SHR were administered ramipril at a dose of 5 mg / kg, candesartan 4 mg / kg and corvitin a dose of 50 mg/kg, and conducted combined therapy ramipril and corvitin, candesartan and corvitin. Drugs were administered for 7 days. State prooxidative-antioxidant system in the heart, liver, and kidney was estimated by the level of malondialdehyde (MDA) and has a diene conjugates (DC), the background activity of antioxidant enzymes: superoxiddismutase (SOD), glutathione peroxidase (TRP), of catalase (CT). The results of the study. Monotherapy with ramipril exacerbate the pathological process in the examined structures (kidney, heart, liver) and caused a decline in the level of antioxidant enzymes for the same level of malonic aldehyde and diene conjugates. Treatment with candesartan showed a more positive trend in reducing the level of products peroxidation and activation of superoxide dismutase, slightly increased the level of catalase remained unchanged and the activity of glutathione peroxidase. Combination therapy with carnitin significantly changed the indicators oxidative-antioxidant homeostasis in the direction of growth of activity of enzymes catalase and superoxide dismutase on the background of significant decrease of the products of barbituric acid. The most marked improvement was noted in the myocardium of the left ventricle and kidney in combination therapy with candesartan and corvitin. Conclusions. Application of corvitin in combination with antihypertensive drugs demonstrated protective effect. Increased level of blood pressure not only positive dynamics of combination therapy but also pleiotropy effect of corvitin.

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Quercetin protects the vascular endothelium against iron overload damages via ROS/ADMA/DDAHⅡ/eNOS/NO pathway

Cited by 46 publications

References 57 publications

Quercetin Alleviates Ferroptosis of Pancreatic β Cells in Type 2 Diabetes

Quercetin Alleviates Ferroptosis of Pancreatic β Cells in Type 2 Diabetes

Revisiting Tumors and the Cardiovascular System: Mechanistic Intersections and Divergences in Ferroptosis

Зміни Проокисно-Антиоксидантної Системи У Щурів Серії SHR При Лікуванні Гіпотензивними Препаратами (Раміприлом І Кандесартаном) В Комбінації З Корвітином

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