The genotoxic potential of mixed nitrosamines in drinking water involves oxidative stress and Nrf2 activation

2021 ◽  
pp. 128010
Author(s):  
Lei Dong ◽  
Zhiqiang Jiang ◽  
Lili Yang ◽  
Fen Hu ◽  
Weiwei Zheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Drinking Water ◽  
Genotoxic Potential ◽  
Nrf2 Activation

Iron Metabolism in the Human Body and Setting its Hygienic Limits for Drinking Water. Review. Part 2

2020 ◽  
Vol 99 (5) ◽  
pp. 504-508
Author(s):  
Natalija A. Egorova ◽  
N. V. Kanatnikova
Keyword(s):  
Oxidative Stress ◽  
Drinking Water ◽  
Iron Overload ◽  
Iron Metabolism ◽  
Subcutaneous Tissue ◽  
Allergic Diseases ◽  
The Body ◽  
Urogenital System ◽  
High Iron Content ◽  
Labile Iron Pool

Iron is an assential element for the growth, division, differentiation and functioning of any cell in the body. Iron is virtually important for human and danger at the same time, because with excessive accumulation it causes oxidative stress with formation of highly active oxygen radicals and reactive form of nitrogen that can destroy cell membranes, proteins, nucleic acids, reduce cell viability, with, according to modern concepts, can contribute to the development of many diseases (cardiovascular, rheumatic, gastrointestinal, neurodegenerative, oncological, metabolic and others), and also accelerate the aging process. Part 1 of this review discussed the issues of iron metabolism in human, including its regulation at the cellular and systemic levels, the intake, transport, use, accumulation and export of iron in cells, the role of the labile iron pool in the cytoplasm of cells and plasma non-transferrin bound iron. Data are provided on the causes, frequency and significance of iron overload in the formation of free radicals and the development of oxidative stress. Part 2 of the review provides information on diseases associated with iron overload as well as information on ferroptosis - a new type of iron-dependent regulated cell death. Attention is paid to the works of domestic authors, where it was found that prolonged use of drinking water with a high iron content is unfavorable for the population and leads to an increase in the overall incidence, the development of the diseases of the blood, skin and subcutaneous tissue, musculoskeletal system, digestive system, urogenital system, and allergic diseases. Separate publications are cited on the possibility of a negative effect of iron at concentrations in water of 0.3 mg/l and lower. The material of the review emphasizes the preventive significance of caution attitude to regulating iron in the water in the Russian Federation, where 1/3 of the population uses iron-containing water for drinking, and substantiate the feasibility of establishing a hygienic limit for iron in water not higher than 0.3 mg/l.

Effect of Turmeric and Ginger on Lipid Profile in Male Rats Exposed to Oxidative Stress

2019 ◽  
Vol 10 (01) ◽  
Author(s):  
Eman A. Al-Rekabi ◽  
Dheyaa K. Alomer ◽  
Rana Talib Al-Muswie ◽  
Khalid G. Al-Fartosi
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Drinking Water ◽  
Lipid Profile ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Male Rats ◽  
Control Group ◽  
Very Low Density Lipoprotein ◽  
Low Density

The present study aimed to investigate the effect of turmeric and ginger on lipid profile of male rats exposed to oxidative stress induced by hydrogen peroxide H2O2 at a concentration of 1% given with consumed drinking water to male rats. Methods: 200 mg/kg from turmeric and ginger were used, and the animals were treatment for 30 days. Results: the results showed a significant increase in cholesterol, triglycerides, low density lipoprotein (LDL), very low density lipoprotein (VLDL), whereas it explained a significant decrease in high density lipoprotein (HDL) of male rats exposed to oxidative stress when compared with control group. the results showed a significant decrease in cholesterol, triglycerides, (LDL), (VLDL), whereas it explained a significant increase in (HDL) of rats treated with turmeric and ginger at dose 200 mg/kg when compared with male rats exposed to oxidative stress.

scholarly journals Curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at Ser351

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jee-Yun Park ◽  
Hee-Young Sohn ◽  
Young Ho Koh ◽  
Chulman Jo
Keyword(s):  
Oxidative Stress ◽  
Crucial Role ◽  
Curcuma Longa ◽  
Expression Plasmid ◽  
Expression Of Genes ◽  
Nrf2 Activation ◽  
First Time ◽  
Nrf2 Protein ◽  
Endogenous Defense ◽  
In Cells

AbstractCurcumin, a phytochemical extracted from Curcuma longa rhizomes, is known to be protective in neurons via activation of Nrf2, a master regulator of endogenous defense against oxidative stress in cells. However, the exact mechanism by which curcumin activates Nrf2 remains controversial. Here, we observed that curcumin induced the expression of genes downstream of Nrf2 such as HO-1, NQO1, and GST-mu1 in neuronal cells, and increased the level of Nrf2 protein. Notably, the level of p62 phosphorylation at S351 (S349 in human) was significantly increased in cells treated with curcumin. Additionally, curcumin-induced Nrf2 activation was abrogated in p62 knockout (−/−) MEFs, indicating that p62 phosphorylation at S351 played a crucial role in curcumin-induced Nrf2 activation. Among the kinases involved in p62 phosphorylation at S351, PKCδ was activated in curcumin-treated cells. The phosphorylation of p62 at S351 was enhanced by transfection of PKCδ expression plasmid; in contrast, it was inhibited in cells treated with PKCδ-specific siRNA. Together, these results suggest that PKCδ is mainly involved in curcumin-induced p62 phosphorylation and Nrf2 activation. Accordingly, we demonstrate for the first time that curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at S351.

scholarly journals Keap1 deletion accelerates mutant K-ras/p53-driven cholangiocarcinoma

2020 ◽  
Vol 318 (3) ◽  
pp. G419-G427 ◽  
Author(s):  
Tatsuhide Nabeshima ◽  
Shin Hamada ◽  
Keiko Taguchi ◽  
Yu Tanaka ◽  
Ryotaro Matsumoto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cancer Progression ◽  
Stress Responses ◽  
Target Genes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Related Factor ◽  
Loss Of Function ◽  
P53 Expression ◽  
Nrf2 Activation

The activation of the Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) pathway contributes to cancer progression in addition to oxidative stress responses. Loss-of-function Keap1 mutations were reported to activate Nrf2, leading to cancer progression. We examined the effects of Keap1 deletion in a cholangiocarcinoma mouse model using a mutant K-ras/ p53 mouse. Introduction of the Keap1 deletion into liver-specific mutant K-ras/ p53 expression resulted in the formation of invasive cholangiocarcinoma. Comprehensive analyses of the gene expression profiles identified broad upregulation of Nrf2-target genes such as Nqo1 and Gstm1 in the Keap1-deleted mutant K-ras/ p53 expressing livers, accompanied by upregulation of cholangiocyte-related genes. Among these genes, the transcriptional factor Sox9 was highly expressed in the dysplastic bile duct. The Keap-Nrf2-Sox9 axis might serve as a novel therapeutic target for cholangiocarcinoma. NEW & NOTEWORTHY The Keap1-Nrf2 system has a wide variety of effects in addition to the oxidative stress response in cancer cells. Addition of the liver-specific Keap1 deletion to mice harboring mutant K-ras and p53 accelerated cholangiocarcinoma formation, together with the hallmarks of Nrf2 activation. This process involved the expansion of Sox9-positive cells, indicating increased differentiation toward the cholangiocyte phenotype.

scholarly journals Effects of IRW and IQW on Oxidative Stress and Gut Microbiota in Dextran Sodium Sulfate-Induced Colitis

2018 ◽  
Vol 51 (1) ◽  
pp. 441-451 ◽  
Author(s):  
Gang Liu ◽  
Wenxin Yan ◽  
Sujuan  Ding ◽  
Hongmei Jiang ◽  
Yong Ma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Drinking Water ◽  
Gut Microbiota ◽  
Sodium Sulfate ◽  
Dextran Sodium Sulfate ◽  
Daily Weight Gain ◽  
Control Group ◽  
Unrestricted Access ◽  
Hematoxylin And Eosin ◽  
Colitis Model

Background/Aims: There are known links between inflammatory bowel disease (IBD) and changes in the microbiota of the gut and inflammation and oxidative stress. In this study, a colitis model induced by dextran sodium sulfate (DSS) in mice is used to evaluate whether the presence of bioactive peptides IRW (Ile-Arg-Trp) and IQW (Ile-Gln-Trp) peptides is advantageous. Methods: The mice were arbitrarily assigned to the following four groups: (i) control (untreated), (ii) dextran sodium sulfate (DSS) treated, (iii) IRW-DSS treated, and (iv) IQW-DSS treated. For 7 days, the control group subjects had unrestricted access to untreated drinking water, whereas the drinking water supplied to the subjects in the DSS, IRW-DSS, and IQW-DSS groups during this period consisted of 5% DSS solution. The colonic lesions were scored after hematoxylin and eosin staining. Serum antioxidant capacity was analyzed by 2,2’-azino-bis(3-ethylbenz-thiazoline-6-sulfonic acid) (ABTS) radical cation decolorization test and the microbiota in the colonic contents were sequenced by HiSeq2500 PE250. Results: The presence of DSS reduced daily weight gain, enhanced histopathology scores, and inhibited antioxidant enzyme expression. Superoxide dismutase, catalase, and glutathione peroxidase activities in the DSS-induced colitis model were significantly enhanced (P < 0.05) in the presence of dietary IRW and IQW. Furthermore, the Simpson index was significantly increased (P < 0.05) in the presence of dietary IRW and IQW compared to the control group. IRW and IQW increased the abundance of Coprococcus_1, Ruminococcaceae_UCG-014, and Desulfovibrio compared to the control group and DSS group. Furthermore, IQW decreased the abundance of Bacteroides in relation to the control group, but increased Parabacteroides. In addition, IRW increased the level of Anaerotruncus, Oscillibacter, and Ruminiclostridium_9 compared to the control group. Conclusion: This study concludes that the presence of IRW or IQW can mitigate DSS-induced oxidative stress by improving the activities of antioxidant enzymes, increasing intestinal microbial diversity and enhancing the abundance of gut microbiota, which may help maintain the homeostasis of host health and microenvironment in a DSS-induced mouse model, thus providing a potential further treatment for IBD patients.

Role of oxidative stress in age-related reduction of NO-cGMP-mediated vascular relaxation in SHR

2003 ◽  
Vol 285 (3) ◽  
pp. R542-R551 ◽  
Author(s):  
Jason A. Payne ◽  
Jane F. Reckelhoff ◽  
Raouf A. Khalil
Keyword(s):  
Oxidative Stress ◽  
Drinking Water ◽  
Arterial Pressure ◽  
Vascular Relaxation ◽  
Adult Rats ◽  
Vascular Contraction ◽  
Aging Rats ◽  
Age Related ◽  
Nitrite Nitrate ◽  
Late Stages

The incidence of hypertension increases during the late stages of aging; however, the vascular mechanisms involved are unclear. We investigated whether the late stages of aging are associated with impaired nitric oxide (NO)-mediated vascular relaxation and enhanced vascular contraction and whether oxidative stress plays a role in the age-related vascular changes. Aging (16 mo) male spontaneously hypertensive rats (SHR) nontreated or treated for 8 mo with the antioxidant tempol (1 mM in drinking water) or vitamin E (E; 5,000 IU/kg chow) and vitamin C (C; 100 mg · kg-1· day-1in drinking water) and adult (12 wk) male SHR were used. After the arterial pressure was measured, aortic strips were isolated from the rats for measurement of isometric contraction. The arterial pressure and phenylephrine (Phe)-induced vascular contraction were enhanced, and the ACh-induced vascular relaxation and nitrite/nitrate production were reduced in aging compared with adult rats. In aging rats, the arterial pressure was nontreated (188 ± 4), tempol-treated (161 ± 6), and E + C-treated (187 ± 1 mmHg). Phe (10-5M) caused an increase in active stress in nontreated aging rats (14.3 ± 1.0) that was significantly ( P < 0.05) reduced in tempol-treated (9.0 ± 0.7) and E + C-treated rats (9.8 ± 0.6 × 104N/m2). ACh produced a small relaxation of Phe contraction in nontreated aging rats that was enhanced ( P < 0.05) in tempol- and E + C-treated rats. l-NAME (10-4M), inhibitor of NO synthase, or ODQ (10-5M), inhibitor of cGMP production in smooth muscle, inhibited ACh relaxation and enhanced Phe contraction in tempol- and E + C-treated but not the nontreated aging rats. ACh-induced vascular nitrite/nitrate production was not different in nontreated, tempol- and E + C-treated aging rats. Relaxation of Phe contraction with sodium nitroprusside, an exogenous NO donor, was smaller in aging than adult rats but was not different between nontreated, tempol- and E + C-treated aging rats. Thus, during the late stages of aging in SHR rats, an age-related inhibition of a vascular relaxation pathway involving not only NO production by endothelial cells but also the bioavailability of NO and the smooth muscle response to NO is partially reversed during chronic treatment with the antioxidants tempol and vitamins E and C. The data suggest a role for oxidative stress in the reduction of vascular relaxation and thereby the promotion of vascular contraction and hypertension during the late stages of aging.

scholarly journals Sulforaphane Protects against Cardiovascular Disease via Nrf2 Activation

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Yang Bai ◽  
Xiaolu Wang ◽  
Song Zhao ◽  
Chunye Ma ◽  
Jiuwei Cui ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Leucine Zipper ◽  
Defense Mechanism ◽  
Myocardial Damage ◽  
Related Factor ◽  
Anticancer Activities ◽  
Basic Leucine Zipper ◽  
Nrf2 Activation

Cardiovascular disease (CVD) causes an unparalleled proportion of the global burden of disease and will remain the main cause of mortality for the near future. Oxidative stress plays a major role in the pathophysiology of cardiac disorders. Several studies have highlighted the cardinal role played by the overproduction of reactive oxygen or nitrogen species in the pathogenesis of ischemic myocardial damage and consequent cardiac dysfunction. Isothiocyanates (ITC) are sulfur-containing compounds that are broadly distributed among cruciferous vegetables. Sulforaphane (SFN) is an ITC shown to possess anticancer activities by bothin vivoand epidemiological studies. Recent data have indicated that the beneficial effects of SFN in CVD are due to its antioxidant and anti-inflammatory properties. SFN activates NF-E2-related factor 2 (Nrf2), a basic leucine zipper transcription factor that serves as a defense mechanism against oxidative stress and electrophilic toxicants by inducing more than a hundred cytoprotective proteins, including antioxidants and phase II detoxifying enzymes. This review will summarize the evidence from clinical studies and animal experiments relating to the potential mechanisms by which SFN modulates Nrf2 activation and protects against CVD.

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