Special Issue:
Challenges and Opportunities in Metabolic Syndrome
Maria Giuliana Tozzi Ciancarelli
University of L’Aquila – San Salvatore Hospital, Delta Building 6, Loc Coppito, 67100 L’AQUILA – ITALY
Caterina Di Massimo
University of L’Aquila – San Salvatore Hospital, Delta Building 6, Loc Coppito, 67100 L’AQUILA – ITALY
Daniela De Amicis
University of L’Aquila – San Salvatore Hospital, Delta Building 6, Loc Coppito, 67100 L’AQUILA – ITALY
Irene Ciancarelli
University of L’Aquila – San Salvatore Hospital, Delta Building 6, Loc Coppito, 67100 L’AQUILA – ITALY 2. Nova Salus Nursing and Rehabi-litation Center – 67059 Trasacco (L’Aquila) – Italy
Abstract
The Mediterranean diet (MD) is a dietary pattern described by Ancel B. Keys in the 1950s as a typical dietary habit of some populations bordering the Mediterranean sea in the south of Europe characterized by frugal living style. Findings of the Seven Country Study showed that people faced in the Mediterranean area had a reduced incidence of cardiovascular and metabolic disease, cancer and age-related diseases. The mechanisms through which the MD exerts its health benefit and prevents the onset of several diseases are not completely clarified because of various and complex aspects. Several studies suggest that the claimed benefits of the MD dietary pattern is mainly linked to decreased inflammation and oxidative stress, strongly related to each other and involved in many chronic diseases. The high content of compounds with antioxidant and anti-inflammatory activity present in most foods of the MD pattern has been considered effective for the improvement of many functions and parameters, therefore useful for the maintenance of the health status and the prevention of many chronic diseases. However, the extensive metabolism to which antioxidant compounds are subjected, once ingested with foods, reduces their antioxidant activity within the systemic circulation and tissues and their concentrations are very low in comparison with endogenous antioxidants. Foods produced for human nutrition have significant consequences for both the environment and the health of a specific population, and, in turn, the environment may address food choices and affect eating habit. The MD is a sustainable diet model that presents a very low environmental footprint, promotes the bio-diversity and protects human health and well-being. However, we must not ignore the planet changes and global environmental aspects that might convert the MD into a theoretical eating model far away from that described by Keys.
Angela Tsiang
Magda Havas
Trent School of the Environment, Trent University, Peterborough, ON, Canada, K9J 7B8
Abstract
COVID-19-attributed case and death rates for the U.S.A. were analyzed through May 2020 in three ways – for all 50 states, the country’s largest counties, and the largest counties in California – and found to be statistically significantly higher for states and counties with compared to those without 5G millimeter wave (mmW) technology. 5G mmW index was a statistically significant factor for the higher case and rates in all three analyses, while population density, air quality and latitude were significant for only one or two of the analyses. For state averages, cases per million were 79% higher (p = 0.012), deaths per million were 94% higher (p = 0.049), cases per test were 68% higher (p = 0.003) and deaths per test were 81% higher (p = 0.025) for states with vs. without mmW. For county averages, cases per million were 87% higher (p = 0.005) and deaths per million were 165% higher (p = 0.012) for counties with vs. without mmW. While higher population density contributed to the higher mean case and death rates in the mmW states and counties, exposure to mmW had about the same impact as higher density of mmW states on mean case and death rates and about three times as much impact as higher density for mmW counties on mean case and death rates. Based on multiple linear regression, if there was no mmW exposure, case and death rates would be 18-30% lower for 5G mmW states and 39-57% lower for 5G mmW counties. This assessment clearly shows exposure to 5G mmW technology is statistically significantly associated with higher COVID-19 case and death rates in the U.S.A. The mechanism–should this be a causal relationship–may relate to changes in blood chemistry, oxidative stress, an impaired immune response, an altered cardiovascular and/or neurological response.
Angelo Azzi
Tufts University, Boston, MA, USA, School of Graduate Biomedical Pharmacology and Drug Development Program
Abstract
Oxidative stress refers to an imbalance between the production of reactive oxygen species and the ability of the body to detoxify or repair the resulting damage. However, it will be shown that the term “oxidative stress” is often used instead of the correct “oxidative damage”. The term “eustress” has been used for describing beneficial signaling by small amounts of reactive oxygen species, but it will be shown that reactive oxygen species signaling can also promote cancer cell growth. The term “oxidative distress” has been created to describe the negative effects produced on cells, organs, and the entire body by large amounts of reactive oxygen species. However, if the reactive oxygen species are used to kill infectious microorganisms, the result is beneficial. Measurements of oxidative stress in body fluids or tissue specimens are a measure of oxidative damage potentially occurring simultaneously in different cells, tissues, and organs; they only provide a sum of non-separable events, possibly with opposite effects. There is no officially approved therapy to prevent or treat oxidative stress or oxidative damage. This implies that while oxidative stress issues are already a complex challenge for basic biological sciences, in a clinical setting oxidative stress is only a term of convenience with no diagnostic or therapeutic value. A critical appraisal of oxidative stress terminology, quantification, and therapeutic attempts is presented.
Luis-Eder Vargas-Campos
Maestro en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Marco-A. Adams-Reyes
Acapulco de Juárez Guerrero, México. 2 Especialista en Implantología Facultad Centro Oeste Paulista FACOP, Bauru Sao Paulo Brasil.
Julio-Cesar Adams-Ocampo
Maestría en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Juan-Manuel Luna-Gomez
Especialista en Ortodoncia; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Yanet Medina-Rojas
Maestra en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Luis-Martin Vargas-Zuñiga
Doctor en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Abstract
Introduction. – In this review, one of the mechanisms that is generated in inflammation, oxidative stress, was analyzed. Inflammation is an immune system response, it is essential for survival and recovery, but it can cause damage to the body, due to oxidative stress that occurs when there is an imbalance between the production of reactive oxygen species and the body’s ability to neutralize them with Endogenous antioxidants contribute to the development of chronic diseases such as cardiovascular, diabetes, autoimmune diseases, cancer, neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis.
Aim. – Evaluate the literature about inflammation from the basic to the clinical level.
Methodology. – Databases such as MEDLINE/PubMed and ScienceDirect regarding Inflammation were analyzed.
Results. – Despite recent advances in the understanding of inflammation and oxidative stress, there are still important challenges in the study and treatment of these conditions, on the one hand, it is necessary to develop more precise biomarkers to evaluate oxidative stress and inflammation in patients. On the other hand, new therapeutic approaches are needed to modulate inflammation and oxidative stress more effectively and specifically.
Conclusion. – That the study of inflammation and oxidative stress is crucial to understanding the pathophysiological bases of various chronic diseases and that advances in the field of inflammation and oxidative stress have provided new therapeutic perspectives for the treatment and prevention of chronic diseases.
Vincent Dartigue
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Knox Van Dyke
Department of Biochemistry, West Virginia University School of Medicine, Morgantown, WV
Hillar Klandorf
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Kimberly M. Barnes
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Abstract
Selection for rapid growth in poultry can be linked to an exaggerated state of oxidative stress (reactive oxidative species). Reactive oxidative species are kept in balance by endogenous and exogenous antioxidants. Two compounds, conjugated linoleic acid (CLA) and berberine a purified compound from plant root extract have been suggested to ameliorate oxidative stress. A six-week study examined the effect of CLA and berberine supplementation on markers of oxidative-stress in poultry. Day old broiler chickens (n=60) were equally divided into six groups; a control, a CLA group where half of the regular oil used in a standard was substituted for a CLA oil mixture, a berberine group consisting of berberine supplementation, an allopurinol group, a CLA and allopurinol with the same dose as the CLA and allopurinol groups and a berberine and allopurinol group. The allopurinol was added to induce an oxidative stress state. Body weight, plasma uric acid, plasma glucose, and relative gene expression of six endogenous liver antioxidants were measured during the course of the study. The addition of allopurinol to the diet induced an oxidative stress state as measured by a significant reduction in plasma uric acid. There were no significant changes in BW and blood glucose concentrations. There was a 10-fold increase in the relative mRNA expression of superoxide dismutase 2 and 3 as well as glutathione peroxidase 1 and 3 in CLA+ALLO and BRB+ALLO treatment groups. Notably, CLA increased the expression of uncoupling protein 19-fold compared to control, while the addition of allopurinol blocked these changes. In contrast, there was a slight increase in the uncoupling protein in the BRB+ALLO treatment. Despite the increase in mRNA expression of the antioxidants genes, these results suggest that at the dosages administered, CLA and berberine were not effective in reversing the oxidative stress induced by allopurinol.
Max Oliver Mackay Walker
Department of Biochemistry, School of Biomedical Science, University of Otago, Dunedin, New Zealand
Katherine H Hall
Department of General Practice and Rural Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
Katie Peppercorn
Department of Biochemistry, School of Biomedical Science, University of Otago, Dunedin, New Zealand
Warren Perry Tate
Department of Biochemistry, School of Biomedical Science, University of Otago, Dunedin, New Zealand
Abstract
Long COVID is now well accepted as an ongoing post-viral syndrome resulting from infection of a single virus, the pandemic SARS-CoV-2. It mirrors the post-viral fatigue syndrome, Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, a global debilitating illness arising mainly from sporadic geographically-specific viral outbreaks, and from community endemic infections, but also from other stressors. Core symptoms of both syndromes are post-exertional malaise (a worsening of symptoms following mental or physical activity), pervasive fatigue, cognitive dysfunction (brain fog), and sleep disturbance. Long COVID patients frequently also suffer from shortness of breath, relating to the lung involvement of the SARS-CoV-2 virus. There is no universally accepted pathophysiology, or recognized biomarkers yet for Long COVID or indeed for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Clinical case definitions with very similar characteristics for each have been defined. Chronic inflammation, immune dysfunction, and disrupted energy production in the peripheral system has been confirmed in Long COVID and has been well documented in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Neuroinflammation occurs in the brain in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome as shown from a small number of positron emission tomography and magnetic resonance spectroscopy studies, and has now been demonstrated for Long COVID. Oxidative stress, an increase in reactive oxygen and reactive nitrogen species, and free radicals, has long been suggested as a potential cause for many of the symptoms seen in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, resulting from both activation of the brain’s immune system and dysregulation of mitochondrial function throughout the body. The brain as a high producer of energy may be particularly susceptible to oxidative stress. It has been shown in peripheral immune cells that the balanced production of proteins involved in regulation of the reactive oxygen species in mitochondria is disturbed in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Fluctuations in the chronic low level neuroinflammation during the ongoing course of Long COVID as well as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome have been proposed to cause the characteristic severe relapses in patients. This review explores oxidative stress as a likely significant contributor to the pathophysiology of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and the mechanisms by which oxidative stress could cause the symptoms seen in both syndromes. Treatments that could mitigate oxidative stress and thereby lessen the debilitating symptoms to improve the life of patients are discussed.
Miki Kosaka
1.Tsurumi University School of Dental Medicine
2. Tokyo Children’s Rehabilitation Hospital, Japan
Hidenobu Senpuku
National Institute of Infectious Disease
Asami Hagiwara
Tokyo Children’s Rehabilitation Hospital
Yoshiaki Nomura
Tsurumi University School of Dental Medicine
Nobuhiro Hanada
Tsurumi University School of Dental Medicine
Abstract
Individuals with Down syndrome (DS) are known to be highly susceptible to periodontal disease, exhibiting a rapid progression and increased severity in younger age. They are also at high risk for Alzheimer’s disease (AD) with certain risk derived from amyloid-β (Aβ) accumulation. Periodontal disease in DS individuals is related to an impaired immune system, poor oral hygiene, gingival tissue abnormalities, salivary factors, microbial factors and oxidative stress with high levels of radical oxygen resulting in genetic abnormalities. However, simultaneous assessments of these factors were not performed to clear risk factors to periodontal disease in DS individuals. This study investigated relationships among various parameters in oral and systemic diseases in DS and non-DS subjects.
Thirty DS subjects and 38 non-DS subjects were enrolled in this study and their oral hygiene and oral disease status were examined. Unstimulated whole saliva and blood samples were collected to investigate the presence of periodontal bacteria, cariogenic bacteria and opportunistic pathogens; interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α saliva concentrations; and Aβ42 plasma concentrations. Among tested parameters, Aβ42 plasma concentrations, development of periodontal diseases, S. mutans rate, lactobacilli per total streptococci ratio, numbers of Candida and IL-6 and IL-8 saliva concentrations were significantly higher in DS subjects than in control subjects. Additionally, oral disease parameters, except for the decay-missing-filled index, were significantly higher in DS subjects than control subjects. However, no significant difference was observed in periodontal bacteria ratios between DS and control subjects.
Our results demonstrate that DS subjects are more likely to develop periodontal diseases, produce inflammatory cytokines and become infected by opportunistic pathogens in the oral cavity than control subjects. This is likely due to poor oral hygiene and decreased host defense responses rather than infection of pathogenic bacteria or Aβ accumulation.
Subhajit Mahanty
Research Assistant, Department of Zoology, Bankura Sammilani College, Kenduadihi, PIN 722102
Dipankar Saha
Research Assistant, Department of Zoology, Bankura Sammilani College, Kenduadihi, PIN 722102
Soumitra Kumar Choudhuri
Former Emeritus Medical Scientist and Head, dept. of IVCCC, Chittaranjan National Cancer Institute (CNCI), 37 S.P. Mukherjee Road, Kolkata, PIN 700026
Surajit Majumder
Associate Professor, Department of Zoology, Bankura Sammilani College, Kenduadihi, PIN 722102
Abstract
Reactive oxygen species (ROS) are recognized as essential participants in normal cellular processes, while their intricate involvement in the emergence of various diseases, notably cancer, has garnered significant attention. Elevated levels of ROS isassociated with pro-tumorigenic signalling, heightened cell survival, increased proliferation, and DNA damage, thereby making substantial contributions to the genetic instability. Intriguingly, at elevated levels, ROS paradoxically initiate anti-tumorigenic signalling pathways, thereby instigating cell death through oxidative stress. In this comprehensive review, a focus is given on ROS generation, which encompasses both endogenous and exogenous sources that collectively referred to as oxidative stress. To provide a comprehensive understanding, an exploration of the structural, chemical, and biochemical aspects of free radicals is undertaken.Diverse sources contributing to ROS generation, including metal-mediated free radical formation is also discussed. This review additionally conducts an in-depth examination of oxidative stress within the context of cancer. Moreover, noteworthy contributions of key antioxidant enzymes, namely, superoxide dismutase, catalaseand glutathione peroxidase over the multifaceted landscape of carcinogenesis have been discussed, drawing insights from a multitude of studies. Understanding the intricate interplay between pro- and anti-tumorigenic ROS signalling pathways offers a multitude of potential avenues for cancer therapy. The disrupted redox balance observed in cancer cells presents promising opportunities for ROS manipulation, thereby emerging as a viable and innovative treatment strategy. This present review may serve as an invaluable resource, offering profound insights into the multifaceted roles of ROS in cancer while simultaneously highlighting their therapeutic potential, thereby paving the way for novel and effective cancer interventions.
Ryan Dashek
Comparative Medicine Program, Veterinary Pathobiology, University of Missouri-Columbia, MO, USA; Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA
Yusuke Higashi
Medicine, Tulane University School of Medicine, New Orleans, LA, USA
Nitin A. Das
Cardiothoracic Surgery, UT Health, San Antonio, TX, USA
Jacob J. Russell
Comparative Medicine Program, Veterinary Pathobiology, University of Missouri-Columbia, MO, USA; Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA
Luis A. Martinez-Lemus
Department of Biomedical, Biological and Chemical Engineering, University of Missouri-Columbia, MO, USA; Dalton Cardiovascular Center, University of Missouri, Columbia, MO, USA; Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA; Department of Medicine, University of Missouri School of Medicine, Columbia, MO, USA
R. Scott Rector
Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA; Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, USA; Division of Gastroenterology and Hepatology, Department of Medicine, University of Missouri, Columbia, MO, USA
Bysani Chandrasekar
Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA; Dalton Cardiovascular Center, University of Missouri, Columbia, MO, USA; Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA; Department of Medicine, University of Missouri School of Medicine, Columbia, MO, USA
Abstract
Aims: Chronic intermittent hypoxia (IH), a characteristic feature of obstructive sleep apnea (OSA), contributes to cardiovascular diseases, including atherosclerosis, potentially through persistent oxidative stress and inflammation. TRAF3IP2 (TRAF3 Interacting Protein 2) is an oxidative stress-responsive proinflammatory adapter molecule and plays a causal role in a preclinical model of atherosclerosis. Since SGLT2 (Sodium/Glucose Cotransporter 2) inhibitors have shown protective effects in CVD by inhibiting oxidative stress and inflammation, we hypothesized that IH promotes the crosstalk between oxidative stress and TRAF3IP2, resulting in IL-6-dependent human aortic smooth muscle cell (SMC) proliferation, and that these effects are inhibited by the SGLT2 inhibitor empagliflozin.
Materials and methods: Primary human aortic SMC were exposed to various cycles of IH. Normoxia served as a control. To understand the molecular mechanisms underlying IH-induced nitroxidative stress, TRAF3IP2 and IL-6 induction, and SMC proliferation and those targeted by empagliflozin were determined by treating SMC with various pharmacological inhibitors and viral vectors.
Results: IH upregulated TRAF3IP2 expression, TRAF3IP2-dependent superoxide, hydrogen peroxide and nitric oxide generation, NF-kB and HIF-1a activation, IL-6 induction, and SMC proliferation. Exposure to IL-6 by itself induced SMC proliferation in part via TRAF3IP2, IL-6R, gp130, JAK, and STAT3. Further, SMC express SGLT2 at basal conditions, and is upregulated by both IH and IL-6. Importantly, empagliflozin inhibited IH-induced TRAF3IP2 upregulation, reactive oxygen and nitrogen species generation, TRAF3IP2-dependent HIF-1a and NF-kB activation, IL-6 induction, and IL-6-dependent JAK-STAT3-mediated SMC proliferation. Moreover, empagliflozin inhibited IL-6-induced STAT3-dependent SMC proliferation.
Conclusions: These results suggest the therapeutic potential of empagliflozin in IH and inflammatory vascular proliferative diseases associated with OSA.
Raquel B. Busekrus
University of Northern Colorado, Greeley Colorado, USA
David S. Hydock
University of Northern Colorado, Greeley Colorado, USA
Abstract
Introduction: Doxorubicin is an effective chemotherapy drug, but its use is limited by its cytotoxicity. One of doxorubicin’s anticancer mechanisms is generation of reactive oxygen species which may lead to oxidative stress. The kidney, however, is very vulnerable to oxidative stress, and one way to manage oxidative stress is to scavenge reactive oxygen species via antioxidant enzymes. Although doxorubicin-induced oxidative stress has been extensively studied, a viable treatment to attenuate doxorubcin side effects has yet to be found. This study investigated the effect of creatine feeding on catalase, glutathione peroxide, and superoxide dismutase-1 expression in the kidney following doxorubicin treatment.
Methods: Twenty-eight male Sprague-Dawley rats were randomly assigned to four groups, control saline (C+SAL, n=7), control doxorubicin (C+DOX, n=7), creatine saline (Cr+SAL, n=6) and creatine doxorubicin (Cr+DOX, n=8). Control groups were fed normal chow, and creatine groups were fed chow supplemented with 3% creatine. After two weeks of feeding, doxorubicin groups received15 mg/kg doxorubicin whereas saline groups received saline as a placebo. Western blotting was used to access antioxidant enzyme expression in renal tissue.
Results: A significant between group difference was observed with catalase expression, but post hoc testing did not reveal where differences existed. A trend existed toward doxorubicin treatment increasing catalase expression and creatine attenuated this trend. Glutathione peroxidase and superoxide dismutase-1 presented a similar profile as catalase; however, no significant between group differences were observed. There was a trend, however, toward increased expression of glutathione peroxidase and superoxide dismutase-1 in doxorubicin-treated animals that seemed to be attenuated with creatine supplementation.
Conclusion: To our knowledge there are no studies exploring the antioxidant properties of creatine supplementation in the kidney with doxorubicin, and it is possible that creatine may enhance antioxidant properties that can attenuate the negative effects doxorubicin in the kidney. A trend towards antioxidant enzyme normalization promoted by creatine with doxorubicin suggests that creatine might have similar effect to that observed in previous studies using antioxidant drugs.
Jelani I
Department of Chemical Pathology, School of Medical Laboratory Sciences, Usmanu Danfodiyo University, Sokoto P.M.B. 2346, Sokoto, Nigeria
Abdullahi HL
Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Bayero University, Kano, P.M.B. 3011, Kano, Nigeria
Alhassan AJ
Department of Biochemistry, Faculty of Basic Medical Sciences Bayero University, Kano, P.M.B. 3011, Kano, Nigeria
Dalhatu MM
Biochemistry Department, Aliko Dangote University of Science and Technology, Wudil, Kano P.M.B. 3244, Nigeria.
Dangambo MA
Department of Biochemistry, Faculty of Basic Medical Sciences Bayero University, Kano, P.M.B. 3011, Kano, Nigeria
Abacha FZ
Department of Medical Laboratory Science, College of Medical Sciences, University of Maiduguri, P.M.B. 1069, Maiduguri, Nigeria
Haruna S
Department of Medical Laboratory Science, Faculty of Allied Health Science, College of Medicine, Ahmadu Bello University, Zaria, P.M.B. 1096, Samaru Zaria, Nigeria
Mahmud RI
Kebbi State College of Health Sciences and Technology Jega, P.M.B. 9003, Kebbi, Nigeria
Yandutse MI
Department of Chemical Pathology, Federal Teaching Hospital, Katsina, P.M.B. 2121, Katsina, Nigeria
Hamza HD
Department of Chemical Pathology, Federal Teaching Hospital, Katsina, P.M.B. 2121, Katsina, Nigeria
Abdu R
Ministry of Defence, Ship House, P.M.B. 196, Abuja, Nigeria
Musa AH
Department of Medical Laboratory Science, College of Medical Sciences, University of Maiduguri, P.M.B. 1069, Maiduguri, Nigeria
Abstract
Glucose-6-phosphate dehydrogenase deficiency is a significant public health problem that is implicated in the pathogenesis of a number of common diseases via increased oxidative stress and a decrease in the generation of nitric oxide. There is little information about its impact on some organ, hence the need for this research. This was a case-control study carried out on Hausa and Fulani ethnics in Kano. Heparinized 5 ml venous blood specimen were collected from 140 individuals (70 deficient and 70 control) aged between 18-35 years selected for the study to determine the blood levels of some biochemical parameters using standard methods. There were significant increase in transaminases (p<0.001), but significant decrease concentrations of sodium (p<0.05), chloride (p<0.001), alkaline phosphatase (p<0.001) and total protein (p<0.001) whereas there was no statistically significant difference (p>0.05) in the plasma concentration of albumin, total bilirubin, conjugated bilirubin, urea, creatinine, potassium and bicarbonate ions. Our results demonstrate extremely significantly lower (p<0.001 for all) concentration in glutathione reductase, total antioxidants potential, copper, zinc and non-significant decrease (p>0.05) in manganese level of G-6-PD deficient patients compared to controls, whereas malondialdehyde level showed an increasing trend on contrary. However, there were correlations between G-6-PD activity and oxidative stress markers. The findings of the present study suggest that liver and kidneys functions were not altered among people living with G-6-PD deficiency but induce oxidative stress which is not capable of causing organ impairment.
Peter Vajdovich
Department of Clinical Pathology and Oncology, University of Veterinary Medicine, 1078, István u. 2., Budapest, Hungary
Bernadett Szabó
Department of Clinical Pathology and Oncology, University of Veterinary Medicine, 1078, István u. 2., Budapest, Hungary
Noémi Tarpataki
Department of Internal Medicine, University of Veterinary Medicine, 1078, István u. 2., Budapest, Hungary
Judit Jakus
Department of Clinical Pathology and Oncology, University of Veterinary Medicine, 1078, István u. 2., Budapest, Hungary
Abstract
Purpose: Oxidative stress is a contributor to the development of neoplasms. OS is involved in multidrug resistance, adverse events, and outcomes.
Methods: Forty- two dogs with lymphoma have been included in the study, 30 of which were treated by Cyclophosphamide – Hydroxyldaunorubicin® (doxorubicin) – Oncovin® (vincristine) – Prednisolone (CHOP)-based protocol. Tumor samples were excised for histopatholgy, immunophenotyping, Ki67%, and biochemical analyses. Thiobarbituric acid reactive substances (TBARS), reduced and oxidized glutathione (GSH, GSSG), glutathione peroxidase (GSH-Px), Cu-Zn-superoxide dismutase (SOD), ferric reducing ability (FRAP), vitamin-C, -E, retinyl palmitate and trans-retinol in red blood cell hemolysates, lymph node homogenates, and blood plasma have been measured. The results were correlated with the outcome of the chemotherapy.
Results: Median overall survival time (OST), relapse-free period (RFP) were 862 and 280 days, respectively, with adverse effects in 18 cases.
Plasma GSH levels increased with age (dogs from 1 to 6 years vs 9 to 13 years, p = 0.0385). Lymph node FRAP levels were higher in samples with higher Ki67%, and plasma GSH/GSSG ratio was lower in dogs with increased OST and RFP. Plasma retinyl palmitate levels were lower in dogs with increased RFP. Overall survival time was increased with lower lymph node TBARS (cut off: 53 nmol/mg protein), GHS-Px (cut off: 16 U/mg protein), and higher plasma all-trans-retinol (cut off: 4 mg/ml). Relapse-free period was increased with lower lymph node TBARS (cut off: 53 nmol/mg protein), lower FRAP (cut off: 6 µmol/mg) and higher SOD (cut off: 70 U/mg protein). During chemotherapy a gradual increase in plasma vitamin E and C concentrations was detected, while GSH and GSSG showed a decrease before adverse events.
Conclusion: Although oxidative stress parameters varied, some parameters, i.e. TBARS, GSH-Px, SOD, FRAP measured in lymph node samples, and plasma all-trans retinol might be used as prognostic indices.
Akira T Kawaguchi
Department of Innovative Medical Science, Tokai University/ Department of Molecular Chemistry and Biochemistry, Doshisha University
Tatsuhide Tanaka, PhD
Department of Anatomy and Neuroscience, Nara Medical University
Mariko Yamano, PhD
Department of Anatomy and Neuroscience, Nara Medical University
Hideaki Sumiyoshi, PhD
Department of Innovative Medical Science, Tokai University
Hiroaki Kitagishi, PhD
Department of Molecular Chemistry and Biochemistry, Doshisha University
Yoshiyuki Yamada, MD, PhD
Department of Pediatrics, Tokai University
Gen T Kawaguchi, MD
Department of Plastic Surgery, Tokai University
Jacob Bergsland, MD, PhD
Oslo University Hospital
Abstract
Objective: Effects of PEGylated-carboxyhemoglobin bovine (SG) infusion and carbon monoxide (CO) inhalation were compared in a rat model of myocardial infarction (MI).
Methods: Lewis rats with induced MI received either 10 mL/kg of SG or of saline (SL), or 400 ppm CO inhalation (CO) daily for 3 days, 4 doses in total. On the fourth day, all animals had left ventricular (LV) functions studied by pressure-volume relationship analyses or in-situ myocardial gene expression by polymerase-chain reaction (PCR).
Results: Both SG infusion and CO inhalation increased the arterial carboxyhemoglobin fraction to 10%, which decreased the total O2 content by 10% for 3 hours before returning to control level, except for the plasma hemoglobin (Hb) over 200 mg/dL 24 hours later, in SG rats. Four days after MI, the SL and CO rats had enhanced cardiac contraction and relaxation, while the SG rats had LV end-systolic pressure, and the isovolumic contraction as well as relaxation remained suppressed at the post-MI levels. PCR showed significant reductions in in-situ antioxidant transcriptional master regulator (Nrf2), its down-stream antioxidant response genes (Nqo-1), hypoxic signal transduction in SG compared to SL or CO rats with enhanced pro-inflammatory, pro-apoptotic genes, and myocardial damage. These cardiac indices were reversed 4 weeks after MI, when SG had less LV dilatation, dysfunction, and myoglobin loss than those with SL or CO.
Conclusion: The results suggest that repeated SG infusion, but not CO inhalation, generates less oxidative stress, reduces hypoxic responses, supports early hemodynamics, and alleviates cardiac compensation early after MI, resulting in attenuated LV dilatation, dysfunction, and myoglobin loss late after MI in this rat model.
Keywords: Artificial Oxygen Carrier, Myocardial Infarction, HBOCs, Carbon Monoxide, Oxidative Stress, Antioxidant Response genes, Cardiac Function
Jeong-Do Kim
Department of Biological Sciences, Louisiana State University, 202 Life Science Building, Baton Rouge, LA 70803
Young-Sun Yim
Department of Biological Sciences, Louisiana State University, 202 Life Science Building, Baton Rouge, LA 70803
Michal Brylinski
Department of Biological Sciences, Louisiana State University, 202 Life Science Building, Baton Rouge, LA 70803
Raafat El-Maghrabi
Department of Physiology and Biophysics, State University of New York at Stony Brook, School of Medicine, Basic Science Tower, T-6, Room168, Stony Brook, NY, 11794-8661
Yong Lee
Department of Biological Sciences, Louisiana State University, 202 Life Science Building, Baton Rouge, LA 70803
Abstract
To understand PFKFB3 control by covalent modifications, the structure/function effect of protein arginine methyl transferase 1-dependent asymmetric di-methylations at Arg131 and Arg134 (N-CH3) and its relationship to S-glutathionylation at Cys206 (S-Gsh) was investigated. Distinctly from the report that N-CH3 is for protection of PFKFB3 from the APC/C-Cdh-mediated polyubiquitination and proteolysis, an increase in the activity for Fru-2,6-P2 production was shown from a molecular simulation and in-vitro tests. The simulation suggested that N-CH3 would uncouple the Fru-6-P entry turn (-130TRERRH-) from its coupling to the p-helix (-204DKCDRD-) by disabling the interaction between Arg131/134 and Asp207. The uncoupling consequently is likely to facilitate the Fru-6-P binding by enhancing the conformational flexibility.
Confirming the simulation, N-CH3 was shown to cause a 5-fold increase in the specific activity (kcat/Km) mostly through a 4-fold decrease in Kms for Fru-6-P. A similar extent of activation was induced by Asp207àA mutagenesis, which disables the coupling, while the activation by N-CH3 was almost abolished by Arg131àA mutagenesis. More interestingly, PFKFB3 with N-CH3 could be additionally S-glutathionylated at Cys206, when oxidative stress is elevated. When modified by both N-CH3 and S-Gsh, the activity was decreased, as if there was no N-CH3 at all, suggesting that the deactivation completely overrules the activation.
When HeLa cells were treated for the dual modifications of PFKFB3, the overruling deactivation effect of S-Gsh was prevalent, causing decreases in Fru-2,6-P2 levels and increases in glycolytic flux redirected to the pentose phosphate pathway. As a result, the levels of NADPH and reduced glutathione were markedly elevated, enhancing cell viability under the conditions of elevated oxidative stress. Altogether, it is suggested that the functional effect of S-Gsh, which represents a mechanism for survival under detrimental oxidative stress, dominates over the effect of N-CH3, which has been suggested as a mechanism for growth.
Rima Dada
Molecular Reproduction and Genetics Facility, Department of Anatomy, AIIMS, New Delhi, India
Surabhi Gautam
Molecular Reproduction and Genetics Facility, Department of Anatomy, AIIMS, New Delhi, India
Tanuj Dada
Department of Ophthalmology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi, India
Prabhakar Tiwari
Molecular Reproduction and Genetics Facility, Department of Anatomy, AIIMS, New Delhi, India
Manoj Kumar
Molecular Reproduction and Genetics Facility, Department of Anatomy, AIIMS, New Delhi, India
Abstract
Complex and chronic lifestyle disorders have become the leading cause of death and disability worldwide. They involve multiple morbidities necessitating the attention of numerous healthcare facilities as well as community-based care too. Stress and anxiety brought on by the fast-paced life, unhealthy eating habits, sedentary lifestyle, poor quality of life, polypharmacy, and high medical costs have significantly influenced the development of such multimorbid conditions. Most chronic complex diseases share a similar underlying pathology including high levels of stress, inflammatory immune response, persistent activation of the hypothalamo-pituitary-adrenal axis, oxidative stress, accelerated immune-aging, dysregulated blood flow, enhanced apoptosis and accelerated aging with shorter telomeres and DNA damage. These are modifiable factors which can impact disease progression and no single treatment modality in modern medicine can alone impact all these factors. As a result, the treatment must involve an integrated approach that targets both mind and body and each of these factors which form an architectural framework which supports the onset of these complex lifestyle disease and thus though we may enjoy longer lifespan, but it is accompanied by shorter health span. Yoga, a mind-body intervention with Indian roots, strives to bring about the synchronization of physical and mental health by unraveling and switching on the internal pharmacy and maintenance of homeostasis at cellular and molecular level.
