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Pimradasiri Srijiwangsa, Saranyoo Ponnikorn, Kesara Na-Bangchang
BACKGROUND: Cholangiocarcinoma (CCA), an epithelial malignancy of the biliary tree, is one of the aggressive cancers with poor prognosis and unsatisfactory response to chemotherapy with acquired resistance. NAD(P)H-quinone oxidoreductase 1 (NQO1), an antioxidant/detoxifying enzyme, plays important roles in chemo-resistance and proliferation in several cancer cells. The study aimed to investigate the inhibitory effect of β-eudesmol on NQO1 enhanced chemotherapeutic effects of 5-fluorouracil (5-FU) and doxorubicin (DOX) in the high NQO1-expressing human CCA cell line, NQO1-KKU-100...
June 19, 2018: BMC Pharmacology & Toxicology
Wensi Xu, Shunya Saiki, Takumi Myojin, Yujia Liu, Beiwei Zhu, Yoshiyuki Murata, Hitoshi Ashida, Makoto Tsunenaga, Yoshimasa Nakamura
Lycii Fructus is the dried ripe fruits of Lycium chinense and L. barbarum, which has long been used as a traditional food material in East Asia. The purpose of this study was to investigate the role of the indirect antioxidative action in the Lycii fructus extract (LFE)-induced cytoprotective effect in vitro. LFE significantly enhanced the expression of the drug-metabolizing enzyme genes and intracellular glutathione level in mouse hepatoma Hepa1c1c7 cells. LFE stimulated the nuclear translocation of aryl hydrocarbon receptor as well as nuclear factor (erythroid-derived 2)-like 2...
June 18, 2018: Bioscience, Biotechnology, and Biochemistry
L Han, F Batistel, Y Ma, A S M Alharthi, C Parys, J J Loor
The periparturient period is the most critical period during the lactation cycle of dairy cows and is characterized by increased oxidative stress status. The objective of this experiment was to evaluate the effect of supplementing rumen-protected methionine on nuclear factor erythroid 2-like 2 (NFE2L2, formerly NRF2) protein and target gene expression in the mammary gland during the early postpartal period. Multiparous Holstein cows were used in a block design experiment with 30 cows per treatment. Treatments consisting of a basal control diet (control) or the basal diet plus rumen-protected methionine (methionine) were fed from d -28 to 60 relative to parturition...
June 13, 2018: Journal of Dairy Science
Wen-Yan Zhu, Xin Jin, Yong-Chi Ma, Zhi-Biao Liu
Ischemia and oxidative stress play crucial roles in the pathophysiology of sudden sensorineural hearing loss (SSNHL). Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine and serves an important role in hearing function. The present study was designed to evaluate the effect of MIF on oxygen-glucose deprivation (OGD)-induced ototoxicity and to elucidate its molecular mechanism. In HEI-OC1 auditory cells, OGD reduced cell viability and increased supernatant lactate dehydrogenase (LDH) and MIF in a time-dependent manner...
June 13, 2018: Biochemical and Biophysical Research Communications
Jia Yuan, Difen Wang, Ying Liu, Xianjun Chen, Hailing Zhang, Feng Shen, Xu Liu, Jiangquan Fu
BACKGROUND: Several studies have recently found that oxidative stress plays a pivotal role in the pathogenesis of traumatic brain injury (TBI) and may represent a target in TBI treatment. Hydrogen-rich water was recently shown to exert neuroprotective effects in various neurological diseases through its antioxidant properties. However, the mechanisms underlying its effects in TBI are not clearly understood. The purpose of our study was to evaluate the neuroprotective role of hydrogen-rich water in rats with TBI and to elucidate the possible mechanisms underlying its effects...
August 2018: Journal of Surgical Research
Xuegu Xu, Yonghao Cai, Yinfei Yu
The aim of the present study was to investigate the therapeutic effects of carbamyl erythropoietin (CEPO) and safflor yellow (SY) in the treatment of rats with diabetic retinopathy (DR) as well as exploring the mechanism of action. Male SD rats were used to establish a diabetes model and streptozotocin-induced retinopathy was also performed in rats. A total of 126 rats with DR were obtained, and model rats were randomly divided into the model (n=42), experimental (n=42) and control (n=42) groups. The rats in the model group were injected with saline, the rats in the experimental group were treated with CEPO, and the rats in the control group were treated with SY...
July 2018: Experimental and Therapeutic Medicine
Lile Dong, Xu Han, Xufeng Tao, Lina Xu, Youwei Xu, Linlin Fang, Lianhong Yin, Yan Qi, Hua Li, Jinyong Peng
We previously reported the effects of the total flavonoids (TFs) from Rosa laevigata Michx fruit against carbon tetrachloride-induced liver damage, non-alcoholic fatty liver disease, and liver ischemia-reperfusion injury. However, there have been no papers reporting the role of R. laevigata TFs against lipopolysaccharide (LPS)-induced liver injury. In this paper, liver injury in mice was induced by LPS, and R. Laevigata extract was intragastrically administered to the mice for 7 days. Biochemical parameters in serum and liver tissue were examined, and pathological changes were observed by transmission electron microscopy, hematoxylin and eosin (H&E) and Oil Red O staining...
June 8, 2018: Foods (Basel, Switzerland)
Ningyu Huang, Xiaojuan Pei, Wenbo Lin, Jen-Fu Chiu, Tao Tao, Guanwu Li
NAD(P)H:quinone oxidoreductase 1 (NQO1), a phase II flavoenzyme that catalyzes reduction reactions to protect cells against electrophiles and oxidants, is involved in tumorigenesis. Altered methylation of the NQO1 gene has been observed and is speculated to result in aberrant NQO1 expression in rat cells undergoing chemical carcinogenesis, although this has not been proven experimentally. In this study, we first investigated the potential epigenetic mechanisms underlying the phenomenon of NQO1 differential expression in individual subclones of rat arsenic-transformed lung epithelial cells (TLECs)...
June 8, 2018: Acta Biochimica et Biophysica Sinica
Fuqiang Liang, Yajing Fang, Weiwei Cao, Zhuo Zhang, Siyi Pan, Xiaoyun Xu
The current study evaluates the protection and potential mechanisms of tangeretin, a representative polymethoxyflavone (PMF) mainly isolated from the peels of citrus fruits, against tert-Butyl Hydroperoxide (t-BHP)-induced oxidative damage in HepG2 cells. Tangeretin suppressed t-BHP-induced oxidative damage, as evaluated by cell viability, reactive oxygen species (ROS) levels, lactate dehydrogenase (LDH) leakeage and glutathione (GSH) levels. Further mechanistic study showed that tangeretin up-regulated the expression of heme oxygenasae-1 (HO-1) and NAD(P)H quinone oxidoreductase-1 (NQO1)...
June 6, 2018: Journal of Agricultural and Food Chemistry
Saeed Nazari Soltan Ahmad, Nadereh Rashtchizadeh, Hassan Argani, Leila Roshangar, Amir Ghorbani Haghjo, Davoud Sanajou, Fatemeh Panah, Zahra Ashrafi Jigheh, Siavoush Dastmalchi, Mehran Mesgari-Abbasi
Despite being an efficacious anticancer agent, the clinical utility of cisplatin is hindered by its cardinal side effects. This investigation aimed to appraise potential protective impact of dunnione, a natural naphthoquinone pigment with established NQO1 stimulatory effects, on cisplatin nephrotoxicity of rats. Dunnione was administered orally at 10 and 20 mg/kg doses for 4 d and a single injection of cisplatin was delivered at the second day. Renal histopathology, inflammatory/oxidative stress/apoptotic markers, kidney function, and urinary markers of renal injury were assessed...
June 4, 2018: Free Radical Research
Yuan Feng, Ning Li, Hongmei Ma, Bei Bei, Yueqing Han, Gang Chen
Five previously undescribed phenylethyl flavones, together with six known flavones, were isolated from the whole plant of Patrinia villosa. It is the first report of natural flavones bearing phenylethyl groups. Their structures were elucidated by the interpretation of 1D and 2D NMR data. The absolute configurations of the previously undescribed phenylethyl flavones were deduced by analysis of the ECD data. All isolates were investigated for their cytoprotective effects against hydrogen peroxide (H2 O2 )-induced oxidative damage in Caco2 cells for the first time...
May 30, 2018: Phytochemistry
Xian Zhang, Xiang Li, Zhihong Li, Xingsen Wu, Yue Wu, Qidong You, Xiaojin Zhang
Tripartite prodrug 1, composed of an NAD(P)H:quinone oxidoreductase 1 (NQO1)-responsive trigger group, a self-immolative linker, and the active drug 5-fluorouracil (5-FU), was designed and synthesized for site-specific cancer therapy. Upon bioreductive activation by NQO1, 1 can release the parent drug 5-FU specifically in NQO1-overexpressing cancer cells. This prodrug exerts comparable antitumor activity and a more favorable safety profile compared with 5-FU both in vitro and in vivo.
May 31, 2018: Organic Letters
Yong Ling, Qiu-Xing Yang, Yu-Ning Teng, Shi Chen, Wei-Jie Gao, Jing Guo, Pei-Ling Hsu, Yue Liu, Susan L Morris-Natschke, Chin-Chuan Hung, Kuo-Hsiung Lee
Fourteen novel amino-quinoline-5,8-dione derivatives (6a-h and 7a-h) were designed and synthesized by coupling different alkyl- or aryl-amino fragments at the C6- or C7-position of quinoline-5,8-dione. All target compounds showed antiproliferative potency in the low micromolar range in both drug sensitive HeLaS3 and multidrug resistant KB-vin cell lines. Compounds 6h, 6d, 7a, and 7d exhibited more potent antiproliferative effects than the other compounds. Especially, compounds 6d and 7d displayed NQO1-dependent cytotoxicity and competitive NQO1 inhibitory effects in both drug sensitive HeLaS3 and multidrug resistant KB-vin cell lines...
May 18, 2018: European Journal of Medicinal Chemistry
Pei-Shan Wu, Hsiou-Yu Ding, Jui-Hung Yen, Shu-Fen Chen, Kuan-Han Lee, Ming-Jiuan Wu
It was demonstrated that isoflavones can cross the blood-brain barrier, making them desirable candidate agents for the prevention of neurological symptoms. 8-Hydroxydaidzein (8-OHD, 4',7,8-trihydoxyisoflavone) is an isoflavone found only in fermented soy food. Current results showed that 8-OHD inhibited LPS-stimulated production of nitric oxide (NO) and proinflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6, by inhibiting gene expression in BV2 microglial cells. Moreover, 8-OHD markedly quenched reactive oxygen species (ROS) and activated NF-E2-related factor 2 (Nrf2) so as to upregulate expression of Phase II enzymes, including heme oxygenase (HO)-1, NAD(P)H quinone dehydrogenase 1 (NQO1), and the modifier subunit of glutamate cysteine ligase (GCLM)...
May 23, 2018: Journal of Agricultural and Food Chemistry
Ali M El-Halawany, Hossam M Abdallah, Ahmed R Hamed, Hany Ezzat Khalil, Ameen M Almohammadi
BACKGROUND: There are increasing interests in natural compounds for cancer chemoprevention. Blocking agents represent an important class of chemopreventive compounds. They prevent carcinogens from undergoing metabolic activation and thereby suppressing their interaction with cellular macromolecular targets. METHODS: The effect of phenolic compounds isolated from Barleria cristata var. alba as chemopreventive agent was evaluated. The ethyl acetate fraction of B. cristata was subjected to different chromatographic techniques for isolation of its major phenolic compounds...
May 22, 2018: BMC Complementary and Alternative Medicine
Abdel Nasser Hosein, Muhammad Shaalan Beg
PURPOSE OF REVIEW: Pancreatic adenocarcinoma is a leading cause of cancer mortality in western countries with a uniformly poor prognosis. Unfortunately, there has been little in the way of novel therapeutics for this malignancy over the last several decades. Derangements in metabolic circuitry favoring excess glycolysis are increasingly recognized as a key hallmark of cancer. RECENT FINDINGS: The role of alterations in glutamine metabolism in pancreatic tumor progression has been elucidated in animal models and human cells lines, and there has been considerable interest in exploiting these aberrations for the treatment of pancreatic cancer...
May 11, 2018: Current Oncology Reports
Yongliang Chen, Lihong Ye, Wangjian Li, Dongzhang Li, Feng Li
The majority of renal calculi (kidney stones) are calcium stones. Oxidative damage to renal tubular epithelial cells induced by reactive oxygen species (ROS) is the predominant cause of calcium oxalate stone formation. Hyperoside (Hyp) is a flavonol glycoside extracted from medicinal plants and appears to exhibit potent antioxidant activity in various cells. The aim of the present study was to investigate the protective effect of Hyp on renal cells exposed to oxidative stress simulated by oxalic acid (OA), and to determine whether the underlying mechanism involves the nuclear factor E2‑related factor2 (Nrf2)‑antioxidative response element signaling pathway...
May 2, 2018: Molecular Medicine Reports
Dora Ravasz, Gergely Kacso, Viktoria Fodor, Kata Horvath, Vera Adam-Vizi, Christos Chinopoulos
Provision of NAD+ for oxidative decarboxylation of alpha-ketoglutarate to succinyl-CoA by the ketoglutarate dehydrogenase complex (KGDHC) is critical for maintained operation of succinyl-CoA ligase yielding high-energy phosphates, a process known as mitochondrial substrate-level phosphorylation (mSLP). We have shown previously that when NADH oxidation by complex I is inhibited by rotenone or anoxia, mitochondrial diaphorases yield NAD+ , provided that suitable quinones are present (Kiss G et al., FASEB J 2014, 28:1682)...
May 7, 2018: Biochimica et Biophysica Acta
Yan-Ru Li, Guo-Hui Li, Lin Sun, Lin Li, Yue Liu, De-Gang Kong, Shu-Qi Wang, Dong-Mei Ren, Xiao-Ning Wang, Hong-Xiang Lou, Tao Shen
Oxidative stress and inflammation undoubtedly contribute to the pathogenesis of many human diseases. The nuclear transcription factor erythroid 2-related factor (Nrf2) and the nuclear factor κ B (NF- κ B) play central roles in regulation of oxidative stress and inflammation and thus are targets for developing agents against oxidative stress- and inflammation-related diseases. Our previous study indicated that the EtOH extract of Litsea garrettii protected human bronchial epithelial cells against oxidative insult via the activation of Nrf2...
2018: Oxidative Medicine and Cellular Longevity
Wei Zhou, Juan-Hua Quan, Fei-Fei Gao, Hassan Ahmed Hassan Ahmed Ismail, Young-Ha Lee, Guang-Ho Cha
Due to the critical location and physiological activities of the retinal pigment epithelial (RPE) cell, it is constantly subjected to contact with various infectious agents and inflammatory mediators. However, little is known about the signaling events in RPE involved in Toxoplasma gondii infection and development. The aim of the study is to screen the host mRNA transcriptional change of 3 inflammation-related gene categories, PI3K/Akt pathway regulatory components, blood vessel development factors and ROS regulators, to prove that PI3K/Akt or mTOR signaling pathway play an essential role in regulating the selected inflammation-related genes...
April 2018: Korean Journal of Parasitology
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