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3637 KiB

Open AccessArticle

New Mild and Simple Approach to Isothiocyanates: A Class of Potent Anticancer Agents

by Bingling Luo, Jiankang Wang, Xiaobing Li, Wenhua Lu, Jing Yang, Yumin Hu, Peng Huang and Shijun Wen

Molecules 2017, 22(6), 773; https://doi.org/10.3390/molecules22060773 - 1 Jun 2017

Cited by 19 | Viewed by 5738

Abstract

In our current work, acetyl chloride-mediated synthesis of phenethyl isothiocyanate (PEITC) derivatives proves to be convenient and provides the expected products at good to excellent yields. Biological evaluation and structure-activity relationship analysis found that the novel compound 7 showed the best anticancer activity [...] Read more.

In our current work, acetyl chloride-mediated synthesis of phenethyl isothiocyanate (PEITC) derivatives proves to be convenient and provides the expected products at good to excellent yields. Biological evaluation and structure-activity relationship analysis found that the novel compound 7 showed the best anticancer activity against human cancer cell line Panc1 and HGC27 compared with PEITC. Compounds 6 and 7 induced more apoptosis in pancreatic cancer cells but less toxicity in non-cancer cells. Further biological study demonstrated that 7 substantially increased intracellular reactive oxygen species (ROS) and depleted glutathione (GSH), leading to an oxidative stress to kill cancer cell. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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946 KiB

Open AccessArticle

Markers of Oxidative Stress and Antioxidant Defense in Romanian Patients with Type 2 Diabetes Mellitus and Obesity

by Ariana Picu, Laura Petcu, Simona Ştefan, Manuela Mitu, Daniela Lixandru, Constantin Ionescu-Tîrgovişte, Grațiela Grădișteanu Pîrcălăbioru, Felicia Ciulu-Costinescu, Maria-Viorica Bubulica and Mariana Carmen Chifiriuc

Molecules 2017, 22(5), 714; https://doi.org/10.3390/molecules22050714 - 1 May 2017

Cited by 47 | Viewed by 6327

Abstract

Type 2 diabetes mellitus (T2DM) is strongly associated with obesity. The adipose tissue secretes bioactive adipokines leading to low grade inflammation, amplified by oxidative stress, which promotes the formation of advanced glycation end products and eventually leads to dyslipidemia and vascular complications. The [...] Read more.

Type 2 diabetes mellitus (T2DM) is strongly associated with obesity. The adipose tissue secretes bioactive adipokines leading to low grade inflammation, amplified by oxidative stress, which promotes the formation of advanced glycation end products and eventually leads to dyslipidemia and vascular complications. The aim of this study was to correlate anthropometric, biochemical and oxidative stress parameters in newly diagnosed (ND) T2DM patients and to investigate the role of oxidative stress in T2DM associated with obesity. A group of 115 ND- T2DM patients was compared to a group of 32 healthy subjects in terms of clinical, anthropometric, biochemical and oxidative stress parameters. ND-T2DM patients had significantly lower adiponectin, glutathione (GSH) and gluthatione peroxidase (GPx) and elevated insulin, proinsulin, HOMA-IR index, proinsulin/insulin (P/I) and proinsulin/adiponectin (P/A) ratio, fructosamine, and total oxidant status (TOS). The total body fat mass was positively correlated with total oxidant status (TOS). Positive correlations were found between TOS and glycated hemoglobin (HbA1c), and between TOS and glycaemia. Negative correlations were identified between: GPx and glycaemia, GPx and HbA1c, and also between GSH and fructosamine. The total antioxidant status was negatively correlated with the respiratory burst. The identified correlations suggest the existence of a complex interplay between diabetes, obesity and oxidative stress. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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1419 KiB

Open AccessArticle

Chemical Composition, Antioxidant and α-Glucosidase-Inhibiting Activities of the Aqueous and Hydroethanolic Extracts of Vaccinium myrtillus Leaves

by Kristina Bljajić, Roberta Petlevski, Lovorka Vujić, Ana Čačić, Nina Šoštarić, Jasna Jablan, Isabel Saraiva de Carvalho and Marijana Zovko Končić

Molecules 2017, 22(5), 703; https://doi.org/10.3390/molecules22050703 - 28 Apr 2017

Cited by 46 | Viewed by 6317

Abstract

Vaccinium myrtillus (bilberry) leaf is traditionally used in southeastern Europe for the treatment of diabetes. In the present study, the ability of bilberry leaf extracts to inhibit carbohydrate-hydrolyzing enzymes and restore glutathione concentration in Hep G2 cells subjected to glucose-induced oxidative stress was [...] Read more.

Vaccinium myrtillus (bilberry) leaf is traditionally used in southeastern Europe for the treatment of diabetes. In the present study, the ability of bilberry leaf extracts to inhibit carbohydrate-hydrolyzing enzymes and restore glutathione concentration in Hep G2 cells subjected to glucose-induced oxidative stress was investigated. A comprehensive analysis of the antioxidant activity of two bilberry leaf extracts was performed. The aqueous extract showed excellent total antioxidant and chelating activity. Its antioxidant activity in the β-carotene-linoleic acid assay was very good, reaching the activity of the antioxidant standard BHA (93.4 ± 2.3% vs. 95.1 ± 2.4%, respectively). The hydroethanolic extract (ethanol/H₂O, 8:2, v/v), on the other hand, was a better radical scavenger and Fe²⁺ reducing agent. Furthermore, the aqueous extract was able to efficiently increase glutathione concentration in Hep G2 cells subjected to glucose-induced oxidative stress and restore it to the levels observed in non-hyperglycaemic cells. The hydroethanolic extract strongly inhibited α-glucosidase, with the IC₅₀ statistically equal to the antidiabetic drug acarbose (0.29 ± 0.02 mg/mL vs. 0.50 ± 0.01 mg/mL, respectively). Phytochemical analysis revealed the presence of quercetin and kaemferol derivatives, as well as chlorogenic and p-coumaric acid. The study results indicate that V. myrtillus leaf may have promising properties as a supporting therapy for diabetes. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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4560 KiB

Open AccessArticle

TCS2 Increases Olaquindox-Induced Apoptosis by Upregulation of ROS Production and Downregulation of Autophagy in HEK293 Cells

by Daowen Li, Kena Zhao, Xiayun Yang, Xilong Xiao and Shusheng Tang

Molecules 2017, 22(4), 595; https://doi.org/10.3390/molecules22040595 - 7 Apr 2017

Cited by 7 | Viewed by 4684

Abstract

Olaquindox, a feed additive, has drawn public attention due to its potential mutagenicity, genotoxicity, hepatoxicity and nephrotoxicity. The purpose of this study was to investigate the role of tuberous sclerosis complex (TSC2) pathways in olaquindox-induced autophagy in human embryonic kidney 293 (HEK293) cells. [...] Read more.

Olaquindox, a feed additive, has drawn public attention due to its potential mutagenicity, genotoxicity, hepatoxicity and nephrotoxicity. The purpose of this study was to investigate the role of tuberous sclerosis complex (TSC2) pathways in olaquindox-induced autophagy in human embryonic kidney 293 (HEK293) cells. The results revealed that olaquindox treatment reduced the cell viability of HEK293 cells and downregulated the expression of TSC2 in a dose- and time-dependent manner. Meanwhile, olaquindox treatment markedly induced the production of reactive oxygen species (ROS), cascaded to autophagy, oxidative stress, and apoptotic cell death, which was effectively eliminated by the antioxidant N-acetylcysteine (NAC). Furthermore, overexpression of TSC2 attenuated olaquindox-induced autophagy in contrast to inducing the production of ROS, oxidative stress and apoptosis. Consistently, knockdown of TSC2 upregulated autophagy, and decreased olaquindox-induced cell apoptosis. In conclusion, our findings indicate that TSC2 partly participates in olaquindox-induced autophagy, oxidative stress and apoptosis, and demonstrate that TSC2 has a negative regulation role in olaquindox-induced autophagy in HEK293 cells. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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1683 KiB

Open AccessArticle

Antioxidant Properties and Oxidative Transformation of Different Chromone Derivatives

by Evelin Csepanyi, Peter Szabados-Furjesi, Attila Kiss-Szikszai, Lisa M. Frensemeier, Uwe Karst, Istvan Lekli, David D. Haines, Arpad Tosaki and Istvan Bak

Molecules 2017, 22(4), 588; https://doi.org/10.3390/molecules22040588 - 6 Apr 2017

Cited by 28 | Viewed by 5413

Abstract

Nowadays, there is an increase in the application of natural products for the prevention of different disorders or adjuvant substances next to pharmacological treatment. Phytochemicals include different chromone derivatives, which possess a wide spectrum of biological activity. The aim of the present study [...] Read more.

Nowadays, there is an increase in the application of natural products for the prevention of different disorders or adjuvant substances next to pharmacological treatment. Phytochemicals include different chromone derivatives, which possess a wide spectrum of biological activity. The aim of the present study was the investigation of the antioxidant activity, cytotoxicity and oxidative transformation of nine chromone derivatives. First, we investigated the radical scavenging activity (ABTS), the oxygen radical absorption capacity (ORAC) and the ferric reducing antioxidant power (FRAP) of the investigated molecules. The cytotoxic effects of the compounds were tested on H9c2 cell cultures by the MTT assay. Each compound showed a significant ORAC value compared to the reference. However, the compound 865 possess significantly higher FRAP and ABTS activity in comparison with the reference and other tested molecules, respectively. Based on these assays, the compound 865 was selected for further analysis. In these experiments, we investigated the oxidative metabolism of the compound in vitro. The molecule was oxidized by the Fenton reaction, artificial porphyrin and electrochemistry; then, the formed products were identified by mass spectrometry. Four possible metabolites were detected. The results revealed the compound 865 to possess good antioxidant properties and to be stable metabolically; hence, it is worth investigating its effects in vivo. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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1765 KiB

Open AccessArticle

Low-Dose Endotoxin Induces Late Preconditioning, Increases Peroxynitrite Formation, and Activates STAT3 in the Rat Heart

by Márton Pipicz, Gabriella F. Kocsis, László Sárváry-Arantes, Péter Bencsik, Zoltán V. Varga, Péter Ferdinandy and Tamás Csont

Molecules 2017, 22(3), 433; https://doi.org/10.3390/molecules22030433 - 8 Mar 2017

Cited by 11 | Viewed by 5943

Abstract

Administration of low-dose endotoxin (lipopolysaccharide, LPS) 24 h before a lethal ischemia induces pharmacological late preconditioning. The exact mechanism of this phenomenon is not clear. Here we aimed to investigate whether low-dose LPS exerts late effects on peroxynitrite formation and activation of Akt, [...] Read more.

Administration of low-dose endotoxin (lipopolysaccharide, LPS) 24 h before a lethal ischemia induces pharmacological late preconditioning. The exact mechanism of this phenomenon is not clear. Here we aimed to investigate whether low-dose LPS exerts late effects on peroxynitrite formation and activation of Akt, Erk, and STAT3 in the heart. Male Wistar rats were injected with LPS (S. typhimurium; 0.5 mg/kg i.p.) or saline. Twenty-four hours later, hearts were isolated, perfused for 10 min, and then used for biochemical analyses. LPS pretreatment enhanced cardiac formation of the peroxynitrite marker 3-nitrotyrosine. LPS pretreatment also increased cardiac levels of the peroxynitrite precursor nitric oxide (NO) and superoxide. The activities of Ca2+-independent NO synthase and xanthine oxidoreductase increased in LPS-pretreated hearts. LPS pretreatment resulted in significantly enhanced phosphorylation of STAT3 and non-significantly increased phosphorylation of Akt without affecting the activation of Erk. In separate experiments, isolated working hearts were subjected to 30 min global ischemia and 20 min reperfusion. LPS pretreatment significantly improved ischemia-reperfusion-induced deterioration of cardiac function. We conclude that LPS pretreatment enhances cardiac peroxynitrite formation and activates STAT3 24 h later, which may contribute to LPS-induced late preconditioning. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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1255 KiB

Open AccessArticle

Novel Amino-Pyridine Functionalized Chitosan Quaternary Ammonium Derivatives: Design, Synthesis, and Antioxidant Activity

by Qing Li, Caili Zhang, Wenqiang Tan, Guodong Gu and Zhanyong Guo

Molecules 2017, 22(1), 156; https://doi.org/10.3390/molecules22010156 - 18 Jan 2017

Cited by 47 | Viewed by 6754

Abstract

Chemical modification of chitosan is increasingly studied for its potential of providing new applications of chitosan. Here, a group of novel chitosan quaternary ammonium derivatives containing pyridine or amino-pyridine were designed and successfully synthesized through chemical modification of chitosan. Pyridine and amino-pyridine were [...] Read more.

Chemical modification of chitosan is increasingly studied for its potential of providing new applications of chitosan. Here, a group of novel chitosan quaternary ammonium derivatives containing pyridine or amino-pyridine were designed and successfully synthesized through chemical modification of chitosan. Pyridine and amino-pyridine were used as functional groups to improve the antifungal activity of chitosan derivatives. The chitosan derivatives’ antioxidant activity against hydroxyl-radical and 1,1-Diphenyl-2-picrylhydrazyl (DPPH)-radical was tested in vitro. The results showed that chitosan derivatives had better water solubility and stronger antioxidant activity compared with chitosan in all assays. Especially, compounds 3C and 3E (with 3-amino pyridine and 2,3-diamino pyridine as substitute respectively) exhibited stronger hydroxyl-radical and DPPH-radical scavenging ability than other synthesized compounds. These data demonstrated that the synergistic effect of the amino group and pyridine would improve the antioxidant activity of chitosan derivatives, and the position of the amino group on pyridine could influence the antioxidant property of chitosan derivatives. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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6859 KiB

Open AccessArticle

GADD45a Regulates Olaquindox-Induced DNA Damage and S-Phase Arrest in Human Hepatoma G2 Cells via JNK/p38 Pathways

by Daowen Li, Chongshan Dai, Xiayun Yang, Bin Li, Xilong Xiao and Shusheng Tang

Molecules 2017, 22(1), 124; https://doi.org/10.3390/molecules22010124 - 13 Jan 2017

Cited by 28 | Viewed by 9706

Abstract

Olaquindox, a quinoxaline 1,4-dioxide derivative, is widely used as a feed additive in many countries. The potential genotoxicity of olaquindox, hence, is of concern. However, the proper mechanism of toxicity was unclear. The aim of the present study was to investigate the effect [...] Read more.

Olaquindox, a quinoxaline 1,4-dioxide derivative, is widely used as a feed additive in many countries. The potential genotoxicity of olaquindox, hence, is of concern. However, the proper mechanism of toxicity was unclear. The aim of the present study was to investigate the effect of growth arrest and DNA damage 45 alpha (GADD45a) on olaquindox-induced DNA damage and cell cycle arrest in HepG2 cells. The results showed that olaquindox could induce reactive oxygen species (ROS)-mediated DNA damage and S-phase arrest, where increases of GADD45a, cyclin A, Cdk 2, p21 and p53 protein expression, decrease of cyclin D1 and the activation of phosphorylation-c-Jun N-terminal kinases (p-JNK), phosphorylation-p38 (p-p38) and phosphorylation-extracellular signal-regulated kinases (p-ERK) were involved. However, GADD45a knockdown cells treated with olaquindox could significantly decrease cell viability, exacerbate DNA damage and increase S-phase arrest, associated with the marked activation of p-JNK, p-p38, but not p-ERK. Furthermore, SP600125 and SB203580 aggravated olaquindox-induced DNA damage and S-phase arrest, suppressed the expression of GADD45a. Taken together, these findings revealed that GADD45a played a protective role in olaquindox treatment and JNK/p38 pathways may partly contribute to GADD45a regulated olaquindox-induced DNA damage and S-phase arrest. Our findings increase the understanding on the molecular mechanisms of olaquindox. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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5084 KiB

Open AccessArticle

Fenofibrate Therapy Restores Antioxidant Protection and Improves Myocardial Insulin Resistance in a Rat Model of Metabolic Syndrome and Myocardial Ischemia: The Role of Angiotensin II

by Luz Ibarra-Lara, María Sánchez-Aguilar, Alicia Sánchez-Mendoza, Leonardo Del Valle-Mondragón, Elizabeth Soria-Castro, Elizabeth Carreón-Torres, Eulises Díaz-Díaz, Héctor Vázquez-Meza, Verónica Guarner-Lans and María Esther Rubio-Ruiz

Molecules 2017, 22(1), 31; https://doi.org/10.3390/molecules22010031 - 28 Dec 2016

Cited by 26 | Viewed by 6229

Abstract

Renin-angiotensin system (RAS) activation promotes oxidative stress which increases the risk of cardiac dysfunction in metabolic syndrome (MetS) and favors local insulin resistance. Fibrates regulate RAS improving MetS, type-2 diabetes and cardiovascular diseases. We studied the effect of fenofibrate treatment on the myocardic [...] Read more.

Renin-angiotensin system (RAS) activation promotes oxidative stress which increases the risk of cardiac dysfunction in metabolic syndrome (MetS) and favors local insulin resistance. Fibrates regulate RAS improving MetS, type-2 diabetes and cardiovascular diseases. We studied the effect of fenofibrate treatment on the myocardic signaling pathway of Angiotensin II (Ang II)/Angiotensin II type 1 receptor (AT1) and its relationship with oxidative stress and myocardial insulin resistance in MetS rats under heart ischemia. Control and MetS rats were assigned to the following groups: (a) sham; (b) vehicle-treated myocardial infarction (MI) (MI-V); and (c) fenofibrate-treated myocardial infarction (MI-F). Treatment with fenofibrate significantly reduced triglycerides, non-high density lipoprotein cholesterol (non-HDL-C), insulin levels and insulin resistance index (HOMA-IR) in MetS animals. MetS and MI increased Ang II concentration and AT1 expression, favored myocardial oxidative stress (high levels of malondialdehyde, overexpression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4), decreased total antioxidant capacity and diminished expression of superoxide dismutase (SOD)1, SOD2 and catalase) and inhibited expression of the insulin signaling cascade: phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PkB, also known as Akt)/Glut-4/endothelial nitric oxide synthase (eNOS). In conclusion, fenofibrate treatment favors an antioxidant environment as a consequence of a reduction of the Ang II/AT1/NOX4 signaling pathway, reestablishing the cardiac insulin signaling pathway. This might optimize cardiac metabolism and improve the vasodilator function during myocardial ischemia. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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3027 KiB

Open AccessArticle

Neuroprotective Effects of Methyl 3,4-Dihydroxybenzoate against TBHP-Induced Oxidative Damage in SH-SY5Y Cells

by Liang Cai, Li-Fang Wang, Jun-Ping Pan, Xiang-Nan Mi, Zheng Zhang, Hai-Ju Geng, Jia-Hui Wang, Song-Hui Hu, Wei Zhang, Qin Gao, Wu-Tian Wu and Huan-Min Luo

Molecules 2016, 21(8), 1071; https://doi.org/10.3390/molecules21081071 - 22 Aug 2016

Cited by 25 | Viewed by 8904

Abstract

This study investigated the neuroprotective effects of methyl 3,4-dihydroxybenzoate (MDHB) against t-butyl hydroperoxide (TBHP) induced oxidative damage in SH-SY5Y (human neuroblastoma cells) and the underlying mechanisms. SH-SY5Y were cultured in DMEM + 10% FBS for 24 h and pretreated with different concentrations [...] Read more.

This study investigated the neuroprotective effects of methyl 3,4-dihydroxybenzoate (MDHB) against t-butyl hydroperoxide (TBHP) induced oxidative damage in SH-SY5Y (human neuroblastoma cells) and the underlying mechanisms. SH-SY5Y were cultured in DMEM + 10% FBS for 24 h and pretreated with different concentrations of MDHB or N-acetyl-l-cysteine (NAC) for 4 h prior to the addition of 40 μM TBHP for 24 h. Cell viability was analyzed using the methylthiazolyltetrazolium (MTT) and lactate dehydrogenase (LDH) assays. An annexin V-FITC assay was used to detect cell apoptosis rates. The 2′,7′-dichlorofluorescin diacetate (DCFH-DA) assay was used to determine intracellular ROS levels. The activities of antioxidative enzymes (GSH-Px and SOD) were measured using commercially available kits. The oxidative DNA damage marker 8-OHdG was detected using ELISA. Western blotting was used to determine the expression of Bcl-2, Bax, caspase 3, p-Akt and Akt proteins in treated SH-SY5Y cells. Our results showed that MDHB is an effective neuroprotective compound that can mitigate oxidative stress and inhibit apoptosis in SH-SY5Y cells. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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6451 KiB

Open AccessArticle

Curcumin Ameliorates Furazolidone-Induced DNA Damage and Apoptosis in Human Hepatocyte L02 Cells by Inhibiting ROS Production and Mitochondrial Pathway

by Chongshan Dai, Daowen Li, Lijing Gong, Xilong Xiao and Shusheng Tang

Molecules 2016, 21(8), 1061; https://doi.org/10.3390/molecules21081061 - 22 Aug 2016

Cited by 51 | Viewed by 8030

Abstract

Furazolidone (FZD), a synthetic nitrofuran derivative, has been widely used as an antibacterial and antiprotozoal agent. Recently, the potential toxicity of FZD has raised concerns, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on FZD-induced [...] Read more.

Furazolidone (FZD), a synthetic nitrofuran derivative, has been widely used as an antibacterial and antiprotozoal agent. Recently, the potential toxicity of FZD has raised concerns, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on FZD-induced cytotoxicity and the underlying mechanism in human hepatocyte L02 cells. The results showed that curcumin pre-treatment significantly ameliorated FZD-induced oxidative stress, characterized by decreased reactive oxygen species (ROS) and malondialdehyde formation, and increased superoxide dismutase, catalase activities and glutathione contents. In addition, curcumin pre-treatment significantly ameliorated the loss of mitochondrial membrane potential, the activations of caspase-9 and -3, and apoptosis caused by FZD. Alkaline comet assay showed that curcumin markedly reduced FZD-induced DNA damage in a dose-dependent manner. Curcumin pre-treatment consistently and markedly down-regulated the mRNA expression levels of p53, Bax, caspase-9 and -3 and up-regulated the mRNA expression level of Bcl-2. Taken together, these results reveal that curcumin protects against FZD-induced DNA damage and apoptosis by inhibiting oxidative stress and mitochondrial pathway. Our study indicated that curcumin may be a promising combiner with FZD to reduce FZD-related toxicity in clinical applications. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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Review

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Open AccessReview

Conservation of the Keap1-Nrf2 System: An Evolutionary Journey through Stressful Space and Time

by Yuji Fuse and Makoto Kobayashi

Molecules 2017, 22(3), 436; https://doi.org/10.3390/molecules22030436 - 9 Mar 2017

Cited by 132 | Viewed by 11606

Abstract

The Keap1-Nrf2 system is an evolutionarily conserved defense mechanism against oxidative and xenobiotic stress. Its regulatory mechanisms, e.g., stress-sensing mechanism, proteasome-based regulation of Nrf2 activity and selection of target genes, have been elucidated mainly in mammals. In addition, emerging model animals, such as [...] Read more.

The Keap1-Nrf2 system is an evolutionarily conserved defense mechanism against oxidative and xenobiotic stress. Its regulatory mechanisms, e.g., stress-sensing mechanism, proteasome-based regulation of Nrf2 activity and selection of target genes, have been elucidated mainly in mammals. In addition, emerging model animals, such as zebrafish, fruit fly and Caenorhabditis elegans, have been shown to have similar anti-stress systems to mammals, suggesting that analogous defense systems are widely conserved throughout the animal kingdom. Experimental evidence in lower animals provides important information beyond mere laboratory-confined utility, such as regarding how these systems transformed during evolution, which may help characterize the mammalian system in greater detail. Recent advances in genome projects of both model and non-model animals have provided a great deal of useful information toward this end. We herein review the research on Keap1-Nrf2 and its analogous systems in both mammals and lower model animals. In addition, by comparing the amino acid sequences of Nrf2 and Keap1 proteins from various species, we can deduce the evolutionary history of the anti-stress system. This combinatorial approach using both experimental and genetic data will suggest perspectives of approach for researchers studying the stress response. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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Open AccessReview

Effect of Oxidative Stress on ABC Transporters: Contribution to Epilepsy Pharmacoresistance

by Gurpreet Kaur Grewal, Samiksha Kukal, Neha Kanojia, Luciano Saso, Shrikant Kukreti and Ritushree Kukreti

Molecules 2017, 22(3), 365; https://doi.org/10.3390/molecules22030365 - 27 Feb 2017

Cited by 45 | Viewed by 7542

Abstract

Epilepsy is a neurological disorder affecting around 1%–2% of population worldwide and its treatment includes use of antiepileptic drugs to control seizures. Failure to respond to antiepileptic drug therapy is a major clinical problem and over expression of ATP-binding cassette transporters is considered [...] Read more.

Epilepsy is a neurological disorder affecting around 1%–2% of population worldwide and its treatment includes use of antiepileptic drugs to control seizures. Failure to respond to antiepileptic drug therapy is a major clinical problem and over expression of ATP-binding cassette transporters is considered one of the major reasons for pharmacoresistance. In this review, we have summarized the regulation of ABC transporters in response to oxidative stress due to disease and antiepileptic drugs. Further, ketogenic diet and antioxidants were examined for their role in pharmacoresistance. The understanding of signalling pathways and mechanism involved may help in identifying potential therapeutic targets and improving drug response. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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Open AccessReview

Biologic Stress, Oxidative Stress, and Resistance to Drugs: What Is Hidden Behind

by Maria Pantelidou, Karyofyllis Tsiakitzis, Eleni A. Rekka and Panos N. Kourounakis

Molecules 2017, 22(2), 307; https://doi.org/10.3390/molecules22020307 - 17 Feb 2017

Cited by 5 | Viewed by 5363

Abstract

Stress can be defined as the homeostatic, nonspecific defensive response of the organism to challenges. It is expressed by morphological, biochemical, and functional changes. In this review, we present biological and oxidative stress, as well as their interrelation. In addition to the mediation [...] Read more.

Stress can be defined as the homeostatic, nonspecific defensive response of the organism to challenges. It is expressed by morphological, biochemical, and functional changes. In this review, we present biological and oxidative stress, as well as their interrelation. In addition to the mediation in biologic stress (central nervous, immune, and hormonal systems) and oxidative stress, the effect of these phenomena on xenobiotic metabolism and drug response is also examined. It is concluded that stress decreases drug response, a result which seems to be mainly attributed to the induction of hepatic drug metabolizing enzymes. A number of mechanisms are presented. Structure-activity studies are also discussed. Vitamin E, as well as two synthetic novel compounds, seem to reduce both oxidative and biological stress and, consequently, influence drug response and metabolism. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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Open AccessReview

Detection of Reactive Oxygen and Nitrogen Species by Electron Paramagnetic Resonance (EPR) Technique

by Sibel Suzen, Hande Gurer-Orhan and Luciano Saso

Molecules 2017, 22(1), 181; https://doi.org/10.3390/molecules22010181 - 21 Jan 2017

Cited by 98 | Viewed by 9360

Abstract

During the last decade there has been growing interest in physical-chemical oxidation processes and the behavior of free radicals in living systems. Radicals are known as intermediate species in a variety of biochemical reactions. Numerous techniques, assays and biomarkers have been used to [...] Read more.

During the last decade there has been growing interest in physical-chemical oxidation processes and the behavior of free radicals in living systems. Radicals are known as intermediate species in a variety of biochemical reactions. Numerous techniques, assays and biomarkers have been used to measure reactive oxygen and nitrogen species (ROS and RNS), and to examine oxidative stress. However, many of these assays are not entirely satisfactory or are used inappropriately. The purpose of this chapter is to review current EPR (Electron Paramagnetic Resonance) spectroscopy methods for measuring ROS, RNS, and their secondary products, and to discuss the strengths and limitations of specific methodological approaches. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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Open AccessReview

Phenolic Melatonin-Related Compounds: Their Role as Chemical Protectors against Oxidative Stress

by Annia Galano, Romina Castañeda-Arriaga, Adriana Pérez-González, Dun-Xian Tan and Russel J. Reiter

Molecules 2016, 21(11), 1442; https://doi.org/10.3390/molecules21111442 - 29 Oct 2016

Cited by 43 | Viewed by 9884

Abstract

There is currently no doubt about the serious threat that oxidative stress (OS) poses to human health. Therefore, a crucial strategy to maintain a good health status is to identify molecules capable of offering protection against OS through chemical routes. Based on the [...] Read more.

There is currently no doubt about the serious threat that oxidative stress (OS) poses to human health. Therefore, a crucial strategy to maintain a good health status is to identify molecules capable of offering protection against OS through chemical routes. Based on the known efficiency of the phenolic and melatonin (MLT) families of compounds as antioxidants, it is logical to assume that phenolic MLT-related compounds should be (at least) equally efficient. Unfortunately, they have been less investigated than phenols, MLT and its non-phenolic metabolites in this context. The evidence reviewed here strongly suggests that MLT phenolic derivatives can act as both primary and secondary antioxidants, exerting their protection through diverse chemical routes. They all seem to be better free radical scavengers than MLT and Trolox, while some of them also surpass ascorbic acid and resveratrol. However, there are still many aspects that deserve further investigations for this kind of compounds. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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