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Free Radicals and Oxidants in Pathogenesis

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 March 2018) | Viewed by 116422

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Special Issue Editors

Dr. Haobo Li

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Guest Editor

1. Department of Anesthesiology, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
2.Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China
Interests: ischemia reperfusion injury; diabetes; oxidative stress; cardioprotection; reactive oxygen species; long non-coding RNA; Adiponectin; Brg1; FoxO1

Prof. Dr. Zhengyuan Xia

E-Mail Website
Guest Editor

Department of Anesthesiology, The University of Hong Kong, Hong Kong SAR, China
Interests: acute myocardial infarction; antioxidants; diabetes complications; blood pressure; phosphorylation; cardiac function; hypertension; pharmacology; metabolism; diabetes; oxidative stress

Special Issue Information

Dear Colleagues,

The interplay between free radicals and antioxidants is important in the pathogenesis of human diseases and pathologies, such as diabetes and ischemia reperfusion injury. Increases in reactive oxygen species (ROS) and reactive nitrogen species (RNS) production induce oxidative stress where antioxidants interact with free radicals to reduce oxidative stress. An imbalance between the production of ROS/RNS and antioxidant capacity leads to oxidative stress, resulting in cell/organ injury. Thus, effective means that targeting free radicals to reduce ROS/RNS and/or targeting antioxidants to increase antioxidant capacity may protect cell/organ against oxidative stress-induced damage.

We invite investigators to contribute original research articles, as well as review articles that will stimulate the continuing efforts to understand the mechanism underlying oxidative stress-induced cell/organ injury in ischemia reperfusion injury under normal and diseased conditions to develop strategies to treat these pathological conditions. Potential topics include, but are not limited to:

Roles and mechainsms of free radicals and antioxidants in organ (heart, lung, brain, liver, kidney, and/or intestine) ischemia reperfusion injury under normal and diseased conditions (e.g., diabetes and aging)
Cellular protective signaling pathways targeting free radicals and/or antioxidiants that contribute to cellular repairing during ischemia reperfusion injury and the potential interplay between them
Recent advances in preventing ischemia-reperfusion injury with a focus on oxidative stress

Prof. Dr. Zhengyuan Xia
Dr. Haobo Li
Guest Editors

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Keywords

free radical
antioxidant
oxidative stress
ischemia reperfusion injury
diabetes
aging
reactive oxygen species
reactive nitrogen species

Published Papers (13 papers)

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13 pages, 2899 KiB

Open AccessArticle

Diethyl Blechnic, a Novel Natural Product Isolated from Salvia miltiorrhiza Bunge, Inhibits Doxorubicin-Induced Apoptosis by Inhibiting ROS and Activating JNK1/2

by Jie Yu, Hongwei Gao, Chuanhong Wu, Qiong-Ming Xu, Jin-Jian Lu and Xiuping Chen

Int. J. Mol. Sci. 2018, 19(6), 1809; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19061809 - 19 Jun 2018

Cited by 19 | Viewed by 4204

Abstract

Doxorubicin (DOX) is a widely used antineoplastic agent in clinics. However, its clinical application is largely limited by its cardiotoxicity. Diethyl blechnic (DB) is a novel compound isolated from Salvia miltiorrhiza Bunge. Here, we study the effect of DB on DOX-induced cardiotoxicity and its underlying mechanisms. Cellular viability was tested by 3-[-4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and protein level was evaluated by Western blotting. 5,5’,6,6’-tetrachloro-1,1’,3,3’-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining was performed to determine the mitochondrial membrane potential (MMP). Hoechst 33342 staining and TUNEL staining was performed to test the apoptosis. Reactive oxygen species (ROS) generation was investigated by using flow cytometry. DB significantly inhibited DOX-induced apoptosis in H9c2 cells and primary cultured cardiomyocytes. Moreover, DB decreased cell apoptotic morphological changes and reversed the mitochondrial membrane potential induced by DOX. Meanwhile, pre-treatment with DB increased the expression levels of B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra-large (Bcl-xl), and survivin and reduced the expression levels of Bcl-2-associated X protein (Bax), p-p53, cytochrome c (cyt c), and cleaved-caspase 3, 7, 8, 9 in the protein levels in DOX-treated H9c2 cells. Furthermore, DB suppressed ROS generation. The DB-mediated protective effects were accompanied by increased c-Jun N-terminal kinase1/2 (JNK1/2) expression. In addition, SP600125, the inhibitor of JNK1/2, abolished the protective effect of DB. We concluded that DB protected cardiomyocytes against DOX-induced cytotoxicity by inhibiting ROS and activating the JNK1/2 pathway. Therefore, DB is a promising candidate as a cardioprotective agent against DOX-induced cardiotoxicity. Full article

(This article belongs to the Special Issue Free Radicals and Oxidants in Pathogenesis)

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15 pages, 3422 KiB

Open AccessArticle

Epidermal Growth Factor, through Alleviating Oxidative Stress, Protect IPEC-J2 Cells from Lipopolysaccharides-Induced Apoptosis

by Xiaopeng Tang, Bo Liu, Xiangrong Wang, Qifang Yu and Rejun Fang

Int. J. Mol. Sci. 2018, 19(3), 848; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19030848 - 14 Mar 2018

Cited by 69 | Viewed by 6376

Abstract

The epidermal growth factor (EGF) has been widely used for protection of stress-induced intestinal mucosa dysfunction. However, whether EGF would alleviate oxidative injury and reduce apoptosis in porcine intestine is not yet known. Therefore, the aim of this study was to investigate the effect of EGF on lipopolysaccharides (LPS)-induced induction of oxidative stress and ensuing apoptosis in the porcine intestinal epithelial cell line, IPEC-J2. The present study showed that EGF significantly increased cell viability and decreased the LPS-induced induction of apoptosis, dehydrogenase (LDH) release and malonaldehyde (MDA) production. EGF also (i) decreased expression of the pro-apoptotic genes Fas, Bax, Cascase-3, Cascase-8, Cascase-9, and proteins such as P53, Fas, Bax, Caspase3; (ii) increased antiapoptotic protein B-cell lymphoma 2 (Bcl2) expression; (iii) increased mRNA levels of the nuclear factor erythroid 2-related factor 2 (Nrf2) related genes Nrf2, manganese superoxide dismutase (SOD2), catalase (CAT), glutathione peroxidase (GSH-Px), heme oxygenase (HO-1) and quinone oxidoreductase (NQO1); (iv) protein level of Nrf2-realeted proteins Nrf2, HO-1, NQO1; and (v) total antioxidant capacity (T-AOC), CAT, SOD, GSH-Px concentrations. Collectively, our results indicated that EGF enhanced Nrf2 protein expression, and upregulated the expression of phase II metabolizing enzymes (such as HO-1 and NQO1) and antioxidative enzymes (SOD, CAT and GSH-Px) to alleviate oxidative injury, and then protect IPEC-J2 cells from apoptosis induced by LPS. Full article

(This article belongs to the Special Issue Free Radicals and Oxidants in Pathogenesis)

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2656 KiB

Open AccessArticle

Thioredoxin 2 Offers Protection against Mitochondrial Oxidative Stress in H9c2 Cells and against Myocardial Hypertrophy Induced by Hyperglycemia

by Hong Li, Changqing Xu, Quanfeng Li, Xiuxiang Gao, Erkio Sugano, Hiroshi Tomita, Liming Yang and Sa Shi

Int. J. Mol. Sci. 2017, 18(9), 1958; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18091958 - 15 Sep 2017

Cited by 36 | Viewed by 7972

Abstract

Mitochondrial oxidative stress is thought to be a key contributor towards the development of diabetic cardiomyopathy. Thioredoxin 2 (Trx2) is a mitochondrial antioxidant that, along with Trx reductase 2 (TrxR2) and peroxiredoxin 3 (Prx3), scavenges H₂O₂ and offers protection against oxidative stress. Our previous study showed that TrxR inhibitors resulted in Trx2 oxidation and increased ROS emission from mitochondria. In the present study, we observed that TrxR inhibition also impaired the contractile function of isolated heart. Our studies showed a decrease in the expression of Trx2 in the high glucose-treated H9c2 cardiac cells and myocardium of streptozotocin (STZ)-induced diabetic rats. Overexpression of Trx2 could significantly diminish high glucose-induced mitochondrial oxidative damage and improved ATP production in cultured H9c2 cells. Notably, Trx2 overexpression could suppress high glucose-induced atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) gene expression. Our studies suggest that high glucose-induced mitochondrial oxidative damage can be prevented by elevating Trx2 levels, thereby providing extensive protection to the diabetic heart. Full article

(This article belongs to the Special Issue Free Radicals and Oxidants in Pathogenesis)

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2564 KiB

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Mitochondrial Biogenesis in Response to Chromium (VI) Toxicity in Human Liver Cells

by Xiali Zhong, Rita De Cássia da Silveira e Sá and Caigao Zhong

Int. J. Mol. Sci. 2017, 18(9), 1877; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18091877 - 14 Sep 2017

Cited by 31 | Viewed by 6697

Abstract

Hexavalent chromium (Cr(VI)) is a ubiquitous environmental pollutant, which poses a threat to human public health. Recent studies have shown that mitochondrial biogenesis can be activated by inflammatory and oxidative stress. However, whether mitochondrial biogenesis is involved in Cr(VI)-induced hepatotoxicity is unclear. Here, we demonstrated the induction of inflammatory response and oxidative stress, as indicated by upregulation of inflammatory factors and reactive oxygen species (ROS). Subsequently, we demonstrated that mitochondrial biogenesis, comprising the mitochondrial DNA copy number and mitochondrial mass, was significantly increased in HepG2 cells exposed to low concentrations of Cr(VI). Expression of genes related to mitochondrial function complex I and complex V was upregulated at low concentrations of Cr(VI). mRNA levels of antioxidant enzymes, including superoxide dismutase 1 and 2 (SOD1 and SOD2, respectively), kech like ECH associate protein 1 (KEAP1) and nuclear respiratory factor 2 (NRF-2), were also upregulated. Consistent with the above results, mRNA and protein levels of key transcriptional regulators of mitochondrial biogenesis such as the peroxisome-proliferator-activated receptor γ coactivator-1α (PGC-1α), NRF-1 and mitochondrial transcription factor A (TFAM) were increased by low concentrations of Cr(VI) in HepG2 cells. Moreover, we found that PGC-1α and NRF-1 tended to translocate into the nucleus. The expression of genes potentially involved in mitochondrial biogenesis pathways, including mRNA level of silent information regulator-1 (SIRT1), forkhead box class-O (FOXO1), threonine kinase 1 (AKT1), and cAMP response element-binding protein (CREB1), was also upregulated. In contrast, mitochondrial biogenesis was inhibited and the expression of its regulatory factors and antioxidants was downregulated at high and cytotoxic concentrations of Cr(VI) in HepG2 cells. It is believed that pretreatment with α-tocopherol could be acting against the mitochondrial biogenesis imbalance induced by Cr(VI). In conclusion, our study suggests that the homeostasis of mitochondrial biogenesis may be an important cellular compensatory mechanism against Cr(VI)-induced toxicity and a promising detoxification target. Full article

(This article belongs to the Special Issue Free Radicals and Oxidants in Pathogenesis)

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Mobilization of Nuclear Copper by Green Tea Polyphenol Epicatechin-3-Gallate and Subsequent Prooxidant Breakage of Cellular DNA: Implications for Cancer Chemotherapy

by Mohd Farhan, Mohammad Oves, Sandesh Chibber, Sheikh Mumtaz Hadi and Aamir Ahmad

Int. J. Mol. Sci. 2017, 18(1), 34; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18010034 - 26 Dec 2016

Cited by 21 | Viewed by 4829

Abstract

Epidemiological as well as experimental evidence exists in support of chemopreventive and anticancer properties of green tea and its constituents. The gallocatechin, epicatechin-3-gallate is a major polyphenol present in green tea, shown responsible for these effects. Plant-derived polyphenolic compounds are established natural antioxidants which are capable of catalyzing oxidative DNA degradation of cellular DNA, alone as well as in the presence of transition metal ions, such as copper. Here we present evidence to support that, similar to various other polyphenoic compounds, epicatechin-3-gallate also causes oxidative degradation of cellular DNA. Single cell alkaline gel electrophoresis (Comet assay) was used to assess DNA breakage in lymphocytes that were exposed to various concentrations of epicatechin-3-gallate. Inhibition of DNA breakage in the presence of scavengers of reactive oxygen species (ROS) suggested involvement of ROS generation. Addition of neocuproine (a cell membrane permeable Cu(I) chelator) inhibited DNA degradation, dose-dependently, in intact lymphocytes. In contrast, bathocuproine, which does not permeate cell membrane, was observed to be ineffective. We further show that epicatechin-3-gallate degrades DNA in cell nuclei, which can also be inhibited by neocuproine, suggesting mobilization of nuclear copper in this reaction as well. Our results are indicative of ROS generation, possibly through mobilization of endogenous copper ions, and support our long-standing hypothesis of a prooxidant activity of plant-derived polyphenols as a mechanism for their documented anticancer properties. Full article

(This article belongs to the Special Issue Free Radicals and Oxidants in Pathogenesis)

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Review

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40 pages, 778 KiB

Open AccessReview

A Current Overview of the Biological and Cellular Effects of Nanosilver

by Shana J. Cameron, Farah Hosseinian and William G. Willmore

Int. J. Mol. Sci. 2018, 19(7), 2030; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19072030 - 12 Jul 2018

Cited by 127 | Viewed by 8025

Abstract

Nanosilver plays an important role in nanoscience and nanotechnology, and is becoming increasingly used for applications in nanomedicine. Nanosilver ranges from 1 to 100 nanometers in diameter. Smaller particles more readily enter cells and interact with the cellular components. The exposure dose, particle size, coating, and aggregation state of the nanosilver, as well as the cell type or organism on which it is tested, are all large determining factors on the effect and potential toxicity of nanosilver. A high exposure dose to nanosilver alters the cellular stress responses and initiates cascades of signalling that can eventually trigger organelle autophagy and apoptosis. This review summarizes the current knowledge of the effects of nanosilver on cellular metabolic function and response to stress. Both the causative effects of nanosilver on oxidative stress, endoplasmic reticulum stress, and hypoxic stress—as well as the effects of nanosilver on the responses to such stresses—are outlined. The interactions and effects of nanosilver on cellular uptake, oxidative stress (reactive oxygen species), inflammation, hypoxic response, mitochondrial function, endoplasmic reticulum (ER) function and the unfolded protein response, autophagy and apoptosis, angiogenesis, epigenetics, genotoxicity, and cancer development and tumorigenesis—as well as other pathway alterations—are examined in this review. Full article

(This article belongs to the Special Issue Free Radicals and Oxidants in Pathogenesis)

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29 pages, 1881 KiB

Open AccessReview

Oxidative Stress in Preeclampsia and Placental Diseases

by Rajaa Aouache, Louise Biquard, Daniel Vaiman and Francisco Miralles

Int. J. Mol. Sci. 2018, 19(5), 1496; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19051496 - 17 May 2018

Cited by 345 | Viewed by 19033

Abstract

Preeclampsia is a persistent hypertensive gestational disease characterized by high blood pressure and proteinuria, which presents from the second trimester of pregnancy. At the cellular level, preeclampsia has largely been associated with the release of free radicals by the placenta. Placenta-borne oxidative and nitrosative stresses are even sometimes considered as the major molecular determinants of the maternal disease. In this review, we present the recent literature evaluating free radical production in both normal and pathological placentas (including preeclampsia and other major pregnancy diseases), in humans and animal models. We then assess the putative effects of these free radicals on the placenta and maternal endothelium. This analysis was conducted with regard to recent papers and possible therapeutic avenues. Full article

(This article belongs to the Special Issue Free Radicals and Oxidants in Pathogenesis)

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13 pages, 1176 KiB

Open AccessReview

SOD1 in Amyotrophic Lateral Sclerosis: “Ambivalent” Behavior Connected to the Disease

by Orietta Pansarasa, Matteo Bordoni, Luca Diamanti, Daisy Sproviero, Stella Gagliardi and Cristina Cereda

Int. J. Mol. Sci. 2018, 19(5), 1345; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19051345 - 03 May 2018

Cited by 95 | Viewed by 10385

Abstract

In 1993, Rosen and collaborators discovered that the gene encoding SOD1 has mutations in amyotrophic lateral sclerosis (ALS) patients; moreover, these mutations are found in the exon regions, suggesting that their toxic effects are the consequence of protein dysfunction with an increase of oxidative stress. While a clear genetic picture has been delineated, a more complex scenario has been ascribed to the SOD1 protein. On the one hand, some evidence sustains the hypothesis of an additionally toxic role for wild-type SOD1 (WT-SOD1) in the pathogenesis of sporadic ALS. On the other hand, our group identified a discrepancy among WT-SOD1 protein expression levels and mRNA in ALS sporadic patients, thus providing the hypothesis of a re-localization of the “missing” SOD1 in a different sub-cellular compartment, i.e., nucleus, or an aggregation/precipitation in the insoluble fraction. Moreover, our data also indicate an association between longer disease duration and higher amounts of soluble SOD1 within the nucleus, suggesting a possible defensive role of the protein in this compartment. Starting from this evidence, in this review we will attempt to resolve the “ambivalent” behavior of SOD1 in ALS disease and we will try to classify sporadic ALS patients according to a novel biological signature, i.e., SOD localization. Full article

(This article belongs to the Special Issue Free Radicals and Oxidants in Pathogenesis)

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21 pages, 1943 KiB

Open AccessReview

NADPH Oxidases and Mitochondria in Vascular Senescence

by Gloria Salazar

Int. J. Mol. Sci. 2018, 19(5), 1327; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19051327 - 29 Apr 2018

Cited by 84 | Viewed by 11973

Abstract

Aging is the major risk factor in the development of cardiovascular diseases (CVDs), including hypertension, atherosclerosis, and myocardial infarction. Oxidative stress caused by overproduction of reactive oxygen species (ROS) and/or by reduced expression of antioxidant enzymes is a major contributor to the progression of vascular senescence, pathologic remodeling of the vascular wall, and disease. Both oxidative stress and inflammation promote the development of senescence, a process by which cells stop proliferating and become dysfunctional. This review focuses on the role of the mitochondria and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidases Nox1 and Nox4 in vascular senescence, and their contribution to the development of atherosclerosis. Recent findings are reviewed, supporting a critical role of the mitochondrial regulator peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1α (PGC-1α), the inflammatory gene nuclear factor κB (NF-κB), zinc, the zinc transporters (ZnTs) ZnT3 and ZnT10, and angiotensin II (Ang II) in mitochondrial function, and their role in telomere stability, which provides new mechanistic insights into a previously proposed unified theory of aging. Full article

(This article belongs to the Special Issue Free Radicals and Oxidants in Pathogenesis)

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30 pages, 4884 KiB

Open AccessReview

Polyamine Metabolism and Oxidative Protein Folding in the ER as ROS-Producing Systems Neglected in Virology

by Olga A. Smirnova, Birke Bartosch, Natalia F. Zakirova, Sergey N. Kochetkov and Alexander V. Ivanov

Int. J. Mol. Sci. 2018, 19(4), 1219; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19041219 - 17 Apr 2018

Cited by 24 | Viewed by 6712

Abstract

Reactive oxygen species (ROS) are produced in various cell compartments by an array of enzymes and processes. An excess of ROS production can be hazardous for normal cell functioning, whereas at normal levels, ROS act as vital regulators of many signal transduction pathways and transcription factors. ROS production is affected by a wide range of viruses. However, to date, the impact of viral infections has been studied only in respect to selected ROS-generating enzymes. The role of several ROS-generating and -scavenging enzymes or cellular systems in viral infections has never been addressed. In this review, we focus on the roles of biogenic polyamines and oxidative protein folding in the endoplasmic reticulum (ER) and their interplay with viruses. Polyamines act as ROS scavengers, however, their catabolism is accompanied by H₂O₂ production. Hydrogen peroxide is also produced during oxidative protein folding, with ER oxidoreductin 1 (Ero1) being a major source of oxidative equivalents. In addition, Ero1 controls Ca²⁺ efflux from the ER in response to e.g., ER stress. Here, we briefly summarize the current knowledge on the physiological roles of biogenic polyamines and the role of Ero1 at the ER, and present available data on their interplay with viral infections. Full article

(This article belongs to the Special Issue Free Radicals and Oxidants in Pathogenesis)

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2056 KiB

Open AccessReview

Reactive Oxygen Species and NOX Enzymes Are Emerging as Key Players in Cutaneous Wound Repair

by Dominik André-Lévigne, Ali Modarressi, Michael S. Pepper and Brigitte Pittet-Cuénod

Int. J. Mol. Sci. 2017, 18(10), 2149; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18102149 - 15 Oct 2017

Cited by 84 | Viewed by 8905

Abstract

Our understanding of the role of oxygen in cell physiology has evolved from its long-recognized importance as an essential factor in oxidative metabolism to its recognition as an important player in cell signaling. With regard to the latter, oxygen is needed for the generation of reactive oxygen species (ROS), which regulate a number of different cellular functions including differentiation, proliferation, apoptosis, migration, and contraction. Data specifically concerning the role of ROS-dependent signaling in cutaneous wound repair are very limited, especially regarding wound contraction. In this review we provide an overview of the current literature on the role of molecular and reactive oxygen in the physiology of wound repair as well as in the pathophysiology and therapy of chronic wounds, especially under ischemic and hyperglycemic conditions. Full article

(This article belongs to the Special Issue Free Radicals and Oxidants in Pathogenesis)

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470 KiB

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Cytoprotective Effect of the UCP2-SIRT3 Signaling Pathway by Decreasing Mitochondrial Oxidative Stress on Cerebral Ischemia–Reperfusion Injury

by Jing Su, Jie Liu, Xiao-Yu Yan, Yong Zhang, Juan-Juan Zhang, Li-Chao Zhang and Lian-Kun Sun

Int. J. Mol. Sci. 2017, 18(7), 1599; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18071599 - 24 Jul 2017

Cited by 51 | Viewed by 9358

Abstract

Recovered blood supply after cerebral ischemia for a certain period of time fails to restore brain function, with more severe dysfunctional problems developing, called cerebral ischemia–reperfusion injury (CIR). CIR involves several extremely complex pathophysiological processes in which the interactions between key factors at various stages have not been fully elucidated. Mitochondrial dysfunction is one of the most important mechanisms of CIR. The mitochondrial deacetylase, sirtuin 3 (SIRT3), can inhibit mitochondrial oxidative stress by deacetylation, to maintain mitochondrial stability. Uncoupling protein 2 (UCP2) regulates ATP (Adenosine triphosphate) and reactive oxygen species production by affecting the mitochondrial respiratory chain, which may play a protective role in CIR. Finally, we propose that UCP2 regulates the activity of SIRT3 through sensing the energy level and, in turn, maintaining the mitochondrial steady state, which demonstrates a cytoprotective effect on CIR. Full article

(This article belongs to the Special Issue Free Radicals and Oxidants in Pathogenesis)

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1939 KiB

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Redox Properties of Tryptophan Metabolism and the Concept of Tryptophan Use in Pregnancy

by Kang Xu, Hongnan Liu, Miaomiao Bai, Jing Gao, Xin Wu and Yulong Yin

Int. J. Mol. Sci. 2017, 18(7), 1595; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18071595 - 24 Jul 2017

Cited by 34 | Viewed by 10676

Abstract

During pregnancy, tryptophan (Trp) is required for several purposes, and Trp metabolism varies over time in the mother and fetus. Increased oxidative stress (OS) with high metabolic, energy and oxygen demands during normal pregnancy or in pregnancy-associated disorders has been reported. Taking the antioxidant properties of Trp and its metabolites into consideration, we made four hypotheses. First, the use of Trp and its metabolites is optional based on their antioxidant properties during pregnancy. Second, dynamic Trp metabolism is an accommodation mechanism in response to OS. Third, regulation of Trp metabolism could be used to control/attenuate OS according to variations in Trp metabolism during pregnancy. Fourth, OS-mediated injury could be alleviated by regulation of Trp metabolism in pregnancy-associated disorders. Future studies in normal/abnormal pregnancies and in associated disorders should include measurements of free Trp, total Trp, Trp metabolites, and activities of Trp-degrading enzymes in plasma. Abnormal pregnancies and some associated disorders may be associated with disordered Trp metabolism related to OS. Mounting evidence suggests that the investigation of the use of Trp and its metabolites in pregnancy will be meanful. Full article

(This article belongs to the Special Issue Free Radicals and Oxidants in Pathogenesis)

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