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NAD+ AND NQO1

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https://www.readbyqxmd.com/read/29053632/protective-effect-of-flavonoids-from-ziziphus-jujuba-cv-jinsixiaozao-against-acetaminophen-induced-liver-injury-by-inhibiting-oxidative-stress-and-inflammation-in-mice
#1
Weizhen Huang, Yongjie Wang, Xiaoyan Jiang, Yueyue Sun, Zhongxi Zhao, Siying Li
This study was aimed to investigate the chemical composition, antioxidant activities and hepatoprotective effect of flavonoids from Ziziphus jujuba cv. Jinsixiaozao (ZJF). The composition of ZJF was analyzed by high performance liquid chromatography (HPLC) and Liquid chromatography-mass spectrometry (LC-MS), and antioxidant properties were investigated by biological assays in vitro. The hepatoprotective activity of ZJF was evaluated in acetaminophen (APAP)-treated BALB/c mice. Results indicate that ZJF displayed significant antioxidant capacity...
October 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29018782/comparison-of-blueberry-vaccinium-spp-and-vitamin-c-via-antioxidative-and-epigenetic-effects-in-human
#2
Minju Kim, Hyunkyung Na, Hiroshi Kasai, Kazuaki Kawai, Yun-Shan Li, Mihi Yang
BACKGROUND: Chemopreventive effects and the underlying mechanisms of blueberry (Vaccinium spp.) are not clearly understood in human. We hypothesized blueberry would work via antioxidative and epigenetic modulation, which is similar to vitamin C. METHODS: We performed a pilot and non-inferiority study in healthy young women (n = 12), who consumed vitamin C (1 g/d) or 240 mL of blueberry juice (total polyphenols 300 mg and proanthocyanidin 76 mg/d) for 2 weeks. We analyzed 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) levels in their urine, and global and specific DNA methylation at the NAD(P)H quinone oxidoreductase 1 (NQO1), methylenetetrahydrofolate reductase (MTHFR), or DNA methyltransferase 1 (DNMT1) genes in their blood...
September 2017: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/29017857/administration-of-5-methoxyindole-2-carboxylic-acid-that-potentially-targets-mitochondrial-dihydrolipoamide-dehydrogenase-confers-cerebral-preconditioning-against-ischemic-stroke-injury
#3
Jinzi Wu, Rongrong Li, Wenjun Li, Ming Ren, Nopporn Thangthaeng, Nathalie Sumien, Ran Liu, Shaohua Yang, James W Simpkins, Michael J Forster, Liang-Jun Yan
The objective of this study was to investigate a possible role of mitochondrial dihydrolipoamide dehydrogenase (DLDH) as a chemical preconditioning target for neuroprotection against ischemic injury. We used 5-methoxyindole-2-carboxylic acid (MICA), a reportedly reversible DLDH inhibitor, as the preconditioning agent and administered MICA to rats mainly via dietary intake. Upon completion of 4 week's MICA treatment, rats underwent 1h transient ischemia and 24h reperfusion followed by tissue collection. Our results show that MICA protected the brain against ischemic stroke injury as the infarction volume of the brain from the MICA-treated group was significantly smaller than that from the control group...
October 7, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28982598/methyleugenol-protects-against-t-bhp-triggered-oxidative-injury-by-induction-of-nrf2-dependent-on-ampk-gsk3%C3%AE-and-erk-activation
#4
Junfeng Zhou, Xiaoyuan Ma, Yan Cui, Yang Song, Lei Yao, Yuanyuan Liu, Shanshan Li
Methyleugenol (Mlg), a natural ingredient of many herbs and used as a flavoring substance in dietary products, inhibits inflammation and oxidative stress. The aim of the study is to explore the antioxidative potential of Mlg against tert-butyl hydroperoxide (t-BHP)-triggered oxidative injury and the involvement of antioxidative mechanisms. Our findings indicated that Mlg exposure significantly alleviated t-BHP-stimulated cytotoxicity, suppressed reactive oxygen species (ROS) generation, and increased superoxide dismutase (SOD) and glutathione (GSH) levels, which were related to the induction of the glutamate-cysteine ligase catalytic/modifier (GCLC/GCLM) subunit, heme oxygenase-1 (HO-1), and NAD (P) H: quinone oxidoreductase (NQO1) largely dependent upon upregulating the nuclear factor-erythroid 2-related factor 2 (Nrf2) induction, inhibiting the Keap1 protein expression, and heightening the antioxidant response element (ARE) activity...
September 19, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28947488/treatment-with-sulforaphane-produces-antinociception-and-improves-morphine-effects-during-inflammatory-pain-in-mice
#5
Alejandro Redondo, Pablo Anibal Ferreira Chamorro, Gabriela Riego, Sergi Leanez, Olga Pol
The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) exerts potent anti-oxidative and anti-inflammatory effects, however its participation in the modulation of chronic inflammatory pain and on the antinociceptive effects of μ opioid receptor (MOR) agonists has not been evaluated. We investigated whether the induction of Nrf2 could alleviate chronic inflammatory pain, augments the analgesic effects of morphine and mechanisms implicated. In male C57BL/6 mice with inflammatory pain induced by complete Freund's adjuvant (CFA) subplantarly administered, we assessed: 1) antinociceptive actions of the administration of 5 and 10 mg/kg of a Nrf2 activator, sulforaphane (SFN); 2) effects of SFN on the antinociceptive actions of morphine and on protein levels of Nrf2, heme oxygenase 1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) enzymes, microglial activation and inducible nitric oxide synthase (NOS2) over-expression, as well as on mitogen-activated protein kinase (MAPK) and MOR expression in the spinal cord and paw of animals with inflammatory pain...
September 25, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28946766/salvia-miltiorrhiza-lipophilic-fraction-attenuates-oxidative-stress-in-diabetic-nephropathy-through-activation-of-nuclear-factor-erythroid-2-related-factor-2
#6
Lin An, Mei Zhou, Faiz M M T Marikar, Xue-Wen Hu, Qiu-Yun Miao, Ping Li, Jun Chen
Diabetic nephropathy (DN) is a common cause of chronic kidney disease and end-stage renal disease, which can be triggered by oxidative stress. In this study, we investigated the renoprotective effect of the ethyl acetate extract of Salvia miltiorrhiza (EASM) on DN and examined the underlying molecular mechanism. We observed that EASM treatment attenuated metabolic abnormalities associated with hyperglycemic conditions in the experimental DN model. In streptozotocin (STZ)-induced mice, EASM treatment reduced albuminuria, improved renal function and alleviated the pathological alterations within the glomerulus...
2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28939896/mir-155-mediates-arsenic-trioxide-resistance-by-activating-nrf2-and-suppressing-apoptosis-in-lung-cancer-cells
#7
Shiyan Gu, Yanhao Lai, Hongyu Chen, Yuan Liu, Zunzhen Zhang
Arsenic trioxide (ATO) resistance is a challenging problem in chemotherapy. However, the underlying mechanisms remain to be elucidated. In this study, we identified a high level of expression of miR-155 in a human lung adenocarcinoma A549R cell line that is highly resistant to ATO. We showed that the high level of miR-155 was associated with increased levels of cell survival, colony formation, cell migration and decreased cellular apoptosis, and this was mediated by high levels of Nrf2, NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1) and a high ratio of Bcl-2/Bax...
September 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28922594/dose-dependent-response-to-3-nitrobenzanthrone-exposure-in-human-urothelial-cancer-cells
#8
Mario Pink, Nisha Verma, Anna Zerries, Simone Schmitz-Spanke
A product of incomplete combustion of diesel fuel, 3-nitrobenzanthrone (3-NBA), has been classified as a cancer-causing substance. It first gained attention as a potential urinary bladder carcinogen due to the presence of its metabolite in urine and formation of DNA adducts. The aim of the present study was to characterize the dose-response relationship of 3-NBA in human urothelial cancer cell line (RT4) exposed to concentrations ranging from 0.0003 μM (environmentally relevant) to 80 μM by utilizing toxicological and metabolomic approaches...
September 28, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28916726/the-nqo1-bioactivatable-drug-%C3%AE-lapachone-alters-the-redox-state-of-nqo1-pancreatic-cancer-cells-causing-perturbation-in-central-carbon-metabolism
#9
Molly A Silvers, Stanislaw Deja, Naveen Singh, Robert A Egnatchik, Jessica Sudderth, Xiuquan Luo, Muhammad S Beg, Shawn C Burgess, Ralph J DeBerardinis, David A Boothman, Matthew E Merritt
Many cancer treatments, such as those for managing recalcitrant tumors like pancreatic ductal adenocarcinoma, cause off-target toxicities in normal, healthy tissue, highlighting the need for more tumor-selective chemotherapies. β-Lapachone is bioactivated by NAD(P)H:quinone oxidoreductase 1 (NQO1). This enzyme exhibits elevated expression in most solid cancers and therefore is a potential cancer-specific target. β-Lapachone's therapeutic efficacy partially stems from the drug's induction of a futile NQO1-mediated redox cycle that causes high levels of superoxide, then peroxide formation, which damages DNA and causes hyperactivation of poly (ADP-ribose) polymerase (PARP), resulting in extensive NAD+/ATP depletion...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28905938/triptolide-induces-sertoli-cell-apoptosis-in-mice-via-ros-jnk-dependent-activation-of-the-mitochondrial-pathway-and-inhibition-of-nrf2-mediated-antioxidant-response
#10
Yu Wang, Su-Han Guo, Xue-Jun Shang, Li-Sha Yu, Jian-Wei Zhu, Ang Zhao, Yan-Fen Zhou, Guo-Hua An, Qi Zhang, Bo Ma
Triptolide (TP), an oxygenated diterpene, has a variety of beneficial pharmacodynamic activities but its clinical applications are restricted due to severe testicular injury. This study aimed to delineate the molecular mechanisms of TP-induced testicular injury in vitro and in vivo. TP (5-50000 nmol/L) dose-dependently decreased the viability of TM4 Sertoli cells with an IC50 value of 669.5-269.45 nmol/L at 24 h. TP (125, 250, and 500 nmol/L) dose-dependently increased the accumulation of ROS, the phosphorylation of JNK, mitochondrial dysfunction and activation of the intrinsic apoptosis pathway in TM4 cells...
September 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28883796/functions-of-nqo1-in-cellular-protection-and-coq10-metabolism-and-its-potential-role-as-a-redox-sensitive-molecular-switch
#11
REVIEW
David Ross, David Siegel
NQO1 is one of the two major quinone reductases in mammalian systems. It is highly inducible and plays multiple roles in cellular adaptation to stress. A prevalent polymorphic form of NQO1 results in an absence of NQO1 protein and activity so it is important to elucidate the specific cellular functions of NQO1. Established roles of NQO1 include its ability to prevent certain quinones from one electron redox cycling but its role in quinone detoxification is dependent on the redox stability of the hydroquinone generated by two-electron reduction...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28881715/activation-of-the-nrf2-are-signaling-pathway-by-probucol-contributes-to-inhibiting-inflammation-and-neuronal-apoptosis-after-spinal-cord-injury
#12
Zipeng Zhou, Chang Liu, Shurui Chen, Haosen Zhao, Kang Zhou, Wei Wang, Yajiang Yuan, Zhuo Li, Yue Guo, Zhaoliang Shen, Xifan Mei
The nuclear erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway plays an essential role in the cellular antioxidant and anti-inflammatory responses. Spinal cord injury (SCI) results in a massive release of inflammatory factors and free radicals, which seriously compromise nerve recovery and axon regeneration. In this study, we examined the efficacy of probucol on anti-inflammatory responses and functional recovery after SCI by activating the Nrf2/ARE signaling pathway. We also investigated the mechanism by which inflammation is inhibited in this process...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28868496/pancreatic-mitochondrial-complex-i-exhibits-aberrant-hyperactivity-in-diabetes
#13
Jinzi Wu, Xiaoting Luo, Nopporn Thangthaeng, Nathalie Sumien, Zhenglan Chen, Margaret A Rutledge, Siqun Jing, Michael J Forster, Liang-Jun Yan
It is well established that NADH/NAD(+) redox balance is heavily perturbed in diabetes, and the NADH/NAD(+) redox imbalance is a major source of oxidative stress in diabetic tissues. In mitochondria, complex I is the only site for NADH oxidation and NAD(+) regeneration and is also a major site for production of mitochondrial reactive oxygen species (ROS). Yet how complex I responds to the NADH/NAD(+) redox imbalance and any potential consequences of such response in diabetic pancreas have not been investigated...
September 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28865326/hydrogen-sulfide-attenuates-calcification-of-vascular-smooth-muscle-cells-via-keap1-nrf2-nqo1-activation
#14
Parisa Aghagolzadeh, Ramin Radpour, Matthias Bachtler, Harry van Goor, Edward R Smith, Adam Lister, Alex Odermatt, Martin Feelisch, Andreas Pasch
BACKGROUND AND AIMS: Vascular calcification is a common health problem related to oxidative stress, inflammation, and circulating calciprotein particles (CPP). Hydrogen sulfide is an endogenous signaling molecule with antioxidant properties and potential for drug development targeting redox signaling. Yet, its molecular mechanisms of action in vascular smooth muscle cell (VSMC) calcification have not been delineated. We therefore sought to identify key pathways involved in the calcification-inhibitory properties of sulfide employing our recently developed CPP-induced VSMC calcification model...
August 19, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28863281/aging-related-decline-in-the-induction-of-nrf2-regulated-antioxidant-genes-in-human-bronchial-epithelial-cells
#15
Lulu Zhou, Hongqiao Zhang, Kelvin J A Davies, Henry Jay Forman
Evidence from animal studies suggests that stress-induced increases in Nrf2-regulated antioxidant gene expression, a critical mechanism of cellular protection, declines with aging. This study examined whether this also occurs in humans. We measured the basal and inducible levels of Nrf2-regulated antioxidant genes in human bronchial epithelial (HBE) cells from subjects of young adult (21-29 years) and older (60-69 years) non-smokers, and explored factors affecting expresion. The basal expression of three representative Nrf2-regulated genes, the catalytic and modulator subunits of glutamate cysteine ligase (GCLC and GCLM, respectively), and NAD(P)H quinone oxidoreductase 1 (NQO1), was higher in cells from the older donors compared with cells from the young adult donors...
August 24, 2017: Redox Biology
https://www.readbyqxmd.com/read/28846887/attenuation-of-cyclosporine-a-induced-nephrotoxicity-by-schisandrin-b-through-suppression-of-oxidative-stress-apoptosis-and-autophagy
#16
Qiao Lai, Zhengzhong Luo, Chunying Wu, Sisi Lai, Hanmei Wei, Tongming Li, Qing Wang, Yang Yu
Cyclosporine A (CsA) is a potent immunosuppressive agent whose clinical usage is limited by nephrotoxicity. Schisandrin B (SchB), isolated from the fruit of Schisandra chinensis, is a natural compound with multiple pharmacological activities that has been shown to attenuate organ injury caused by CsA. Hence, the primary objective of the current study was to evaluate whether SchB has a cytoprotective effect on CsA-induced nephrotoxicity in human proximal tubular epithelial cell line (HK-2). This study demonstrated that pre-incubation of HK-2 cells with 2...
November 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28833669/a-tumor-specific-cascade-amplification-drug-release-nanoparticle-for-overcoming-multidrug-resistance-in-cancers
#17
Mingzhou Ye, Yuxin Han, Jianbin Tang, Ying Piao, Xiangrui Liu, Zhuxian Zhou, Jianqing Gao, Jianghong Rao, Youqing Shen
A cascade amplification release nanoparticle (CARN) is constructed by the coencapsulation of β-lapachone and a reactive-oxygen-species (ROS)-responsive doxorubicin (DOX) prodrug, BDOX, in polymeric nanoparticles. Releasing β-lapachone first from the CARNs selectively increases the ROS level in cancer cells via NAD(P)H:quinone oxidoreductase-1 (NQO1) catalysis, which induces the cascade amplification release of DOX and overcomes multidrug resistance (MDR) in cancer cells, producing a remarkably improved therapeutic efficacy against MDR tumors with minimal side effects...
August 21, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28816586/oxidative-stress-in-the-visceral-fat-is-elevated-in-postmenopausal-women-with-gynecologic-cancer
#18
Megumi Narumi, Kazuhiro Takahashi, Hizuru Yamatani, Manabu Seino, Keiko Yamanouchi, Tsuyoshi Ohta, Toshifumi Takahashi, Hirohisa Kurachi, Satoru Nagase
OBJECTIVES: This study aimed to evaluate differences in oxidative stress of visceral fat between premenopausal and postmenopausal women and clarify the antioxidant effect of estrogen on adipocytes. MATERIALS AND METHODS: Abdominal subcutaneous and omental visceral adipose tissues were obtained from 38 patients who underwent gynecological surgery. We measured the sizes of the adipocytes and evaluated the lipid peroxidation levels in the adipose tissues. We investigated whether estrogen inhibited the intracellular reactive oxygen species (ROS) production that was induced by hydrogen peroxide (H2O2) in 3T3-L1 adipocytes...
August 17, 2017: Journal of Women's Health
https://www.readbyqxmd.com/read/28812892/designer-extracts-as-tools-to-balance-estrogenic-and-chemopreventive-activities-of-botanicals-for-women-s-health
#19
Birgit M Dietz, Shao-Nong Chen, René F Ramos Alvarenga, Huali Dong, Dejan Nikolić, Martin Biendl, Richard B van Breemen, Judy L Bolton, Guido F Pauli
Botanical dietary supplements contain multiple bioactive compounds that target numerous biological pathways. The lack of uniform standardization requirements is one reason that inconsistent clinical effects are reported frequently. The multifaceted biological interactions of active principles can be disentangled by a coupled pharmacological/phytochemical approach using specialized ("knock-out") extracts. This is demonstrated for hops, a botanical for menopausal symptom management. Employing targeted, adsorbent-free countercurrent separation, Humulus lupulus extracts were designed for pre- and postmenopausal women by containing various amounts of the phytoestrogen 8-prenylnaringenin (8-PN) and the chemopreventive constituent xanthohumol (XH)...
August 25, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28798861/overexpression-of-brg1-alleviates-hepatic-ischemia-reperfusion-induced-acute-lung-injury-through-antioxidative-stress-effects
#20
Mian Ge, Chaojin Chen, Weifeng Yao, Shaoli Zhou, Fei Huang, Jun Cai, Ziqing Hei
AIM: To investigate whether overexpression of Brahma-related gene-1 (Brg1) can alleviate lung injury induced by hepatic ischemia/reperfusion (HIR) and its precise mechanism. METHODS: Cytomegalovirus-transgenic Brg1-overexpressing (CMV-Brg1) mice and wild-type (WT) C57BL/6 mice underwent HIR. Lung histology, oxidative injury markers, and antioxidant enzyme concentrations in the lung were assessed. The protein expression levels of Brg1, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1) in the lung were analyzed by Western blotting...
2017: Oxidative Medicine and Cellular Longevity
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