ROS as targets for therapeutic intervention of diabetic nephropathy

Size: px
Start display at page:

Download "ROS as targets for therapeutic intervention of diabetic nephropathy"

Transcription

1 36 th Autumn Congress of Korean Diabetes Association September 16-17, 2010, BEXCO, Busan, Korea ROS as targets for therapeutic intervention of diabetic nephropathy Hunjoo Ha Department of Bioinspired Science Division of Life & Pharmaceutical Sciences College of Pharmacy, Ewha Womans University, Seoul, Korea

2 Contents Definition of the term ROS (reactive oxygen species) and OS (oxidative stress) Current understanding of ROS-induced renal injury under hyperglycemia Role of antioxidant defense mechanism under hyperglycemia: catalase, Nrf2 Recent therapeutic advances supporting the role of ROS in diabetic renal injury

3 Sequential reduction of O 2 e O 2 O.- e e 2 H 2 O 2 OH. + OH - e 2H 2 O O 2.- H 2 O 2 OH. O 2 + 4H + 4e 2H 2 O Weak oxidant acting on Fe-S, Fe-Zn centers H O O H Weak oxidant oxidizing sulfur atoms of Cys and Met Strong oxidant indiscriminately damaging DNA, Proteins, Lipids

4 Finkel T et al. Nature 408:239, 2000

5 Oxidative Stress H 2 O 2 O 2.- OH. ROS Antioxidant catalase Defense SOD GPx Mechanisms

6 Definition of the term ROS (reactive oxygen species) and OS (oxidative stress) Current understanding of ROS-induced renal injury under hyperglycemia Role of antioxidant defense mechanism under hyperglycemia: catalase, Nrf2 Recent therapeutic advances supporting the role of ROS in diabetic renal injury

7 Increased ROS under hyperglycemia Ha H et al. JASN 3: Koya D et al. JASN 14:S250, 2003 Unpublished data

8 Markers of OS in human DN

9 ROS-regulated signaling in renal cells under hyperglycemia protein PKC GFAT Lee HB et al. JASN 14:S241-5, 2003

10 Definition of the term ROS (reactive oxygen species) and OS (oxidative stress) Current understanding of ROS-induced renal injury under hyperglycemia Role of antioxidant defense mechanism under hyperglycemia: catalase, Nrf2 Recent therapeutic advances supporting the role of ROS in diabetic renal injury

11 Role of catalase in diabetic nephropathy A heme-containing homotetrameric protein Mainly located in the peroxisomes H 2 O 2 Catalase Fe (Ⅱ) Fenton reaction O 2 + 2H 2 O OH- + OH Ho et al., JBC 279:32804, 2004

12 Characteristics of diabetic cat null mice A B C D WT WT+DM Cat - /- Cat -/- +DM Relative in ncrease WT WT+DM Cat-/- Cat-/-+DM P Cr (mg/d dl) Plasma FFA (mm) n=7~8, Mean ± SE, : p<0.05 vs WT, : p<0.05 vs Cat-/-, : p<0.05 vs WT+DM Unpublished data

13 Glomerular volume & FMA in diabetic cat null mice Glomerular volume 1.5 WT Relative increase WT WT+DM Cat-/- Cat-/-+DM Fractional mesangial area (FMA) Cat-/- FMA 0.9 con DM WT WT+DM Cat-/- Cat-/-+DM n=7~8, Mean ± SE, : p<0.05 vs WT, : p<0.05 vs Cat-/-, : p<0.05 vs WT+DM Unpublished data

14 Renal injury in diabetic cat null mice A TGF-β1/18S B CTGF/18S C BMP7/18S D BMP7 (pg/mg protein) n=7~8, Mean ± SE, : p<0.05 vs WT, : p<0.05 vs Cat-/-, : p<0.05 vs WT+DM D WT WT+DM Cat -/- Cat -/- +DM Unpublished data

15 Oxidative stress in diabetic cat null mice WT Nox4/18S , WT+DM Cat -/- Catalase/ /18S Cat -/- DM SOD2/18S : p<0.05 vs WT, : p<0.05 vs Cat-/-

16

17 Nrf2-Keap1-ARE

18 Diabetic renal injury in Nrf2 null mice

19 Role of ROS in HG-induced Nrf2 activation NAC

20 Definition of the term ROS (reactive oxygen species) and OS (oxidative stress) Current understanding of ROS-induced renal injury under hyperglycemia Role of antioxidant defense mechanism under hyperglycemia: catalase, Nrf2 Recent therapeutic advances supporting the role of ROS in diabetic renal injury

21 Successful antioxidant therapy will depend on Dose of antioxidants Concentration of antioxidants at the site of ROS produced (eg. mitochondria) Plasma half-life of antioxidants Safety and tolerability of antioxidants Type of antioxidants: antioxidants may act as oxidants Oxidative state of patients

22 Bardoxolone methyl: an inducer of Nrf2 Phase IIa trial Renoprotective effect of bardoxolone methyl on diabetes

23 Selective mitochondrial antioxidants: MitoQ Permeable into mitochondria: 100~1000 fold accumulation Adsorbed to the matrix surface of inner membrane Accumulated in the heart, liver, skeletal muscle, kidney, and brain

24

25

26 Human studies with MitoQ Oral bioavailability: 10% Major metabolites in the urine: glucuronide & sulfate conjugation PROTECT study: Parkinson s disease Double-blind study 40, 80 mg/kg for 12 months CLEAR trial: chronic HCV unresponsive to conventional tx Double-blind, randomized study 0, 40, 80 mg/kg for 28 days Common adverse effect: dosedependent nausea

27

28 Haptoglobin (Hp) genotype & DN a hemoglobin binding protein protects against heme-induced ROS 3 genotypes: Hp 1-1, Hp 2-2, and Hp 2-1 Diabetes with Hp 2-2 have 2~5 fold increased risk of CVD.

29 Conclusion Increased generation of ROS in diabetic kidney is convincing. Endogenous antioxidant defense mechanism plays a protective role in DN. Antioxidants acting directly at the mitochondrial site may promise better efficiency than non-specific antioxidants. Pharmacogenomic application may provide a rational for prospective trials to investigate the potential of vigorous antioxidant therapy to ameliorate DN.

30 Characteristics of diabetic cat null mice Body wt (g) Kidney wt /body wt (ratio) Blood glucose (mg/dl) Plasma creatinine (mg/dl) UAE (mg/24 hrs) WT 22.8 ± ± ± ± ± 0.28 WT+DM 19.0 ± ± ± ± ± 0.46 Cat -/ ± ± ± ± ± 0.17 Cat -/- +DM 23.1 ± ± ± ± ± 2.65 n=7~8, Mean ± SE, : p<0.05 vs WT : p<0.05 vs Cat-/-, : p<0.05 vs WT+DM UAE: urinary albumin excretion Unpublished data

31 Renal injury in diabetic cat null mice E αsma/18s H α-sma E-cadherin I αsma/β-actin β-actin G E-cadherin/ /18S Control DM Control DM WT Cat -/- J E-cadher rin/ β-actin D WT WT+DM Cat -/- Cat -/- +DM Unpublished data n=7~8, Mean ± SE, : p<0.05 vs WT, : p<0.05 vs Cat-/-

32 Oxidative stress in diabetic cat null mice No ox4/18s , + Cat talase/18s SO OD2/18S n=7~8, Mean ± SE, : p<0.05 vs WT, : p<0.05 vs Cat-/- Unpublished data

33 Selective mitochondrial antioxidants: MitoQ

34

Diabetic nephropathy (DN) is the leading cause. Catalase Deficiency Accelerates Diabetic Renal Injury Through Peroxisomal Dysfunction

Diabetic nephropathy (DN) is the leading cause. Catalase Deficiency Accelerates Diabetic Renal Injury Through Peroxisomal Dysfunction ORIGINAL ARTICLE Catalase Deficiency Accelerates Diabetic Renal Injury Through Peroxisomal Dysfunction Inah Hwang, 1 Jiyoun Lee, 1 Joo Young Huh, 1 Jehyun Park, 1 Hi Bahl Lee, 2 Ye-Shih Ho, 3 and Hunjoo

More information

Reactive Oxygen species ROS + Anti-oxidants. Dr. Naif Karadsheh

Reactive Oxygen species ROS + Anti-oxidants. Dr. Naif Karadsheh Reactive Oxygen species ROS + Anti-oxidants Dr. Naif Karadsheh Oxygen Toxicity & Free Radicals Biradical O 2 Radical O 2 Non-Radical Radical H 2 O 2 OH ROS O 2 Metabolism and Toxicity O 2 Consumption >90%

More information

Lecture 19 Summary Gestational Diabetes and Complications of Diabetes. Gestational diabetes;

Lecture 19 Summary Gestational Diabetes and Complications of Diabetes. Gestational diabetes; Lecture 19 Summary Gestational Diabetes and Complications of Diabetes Gestational diabetes; - Type of diabetes that only develops during pregnancy Usually diagnosed in late pregnancy Causes high blood

More information

Dr. Hayam Gad Associate Professor of Physiology College of Medicine King Saud University

Dr. Hayam Gad Associate Professor of Physiology College of Medicine King Saud University Dr. Hayam Gad Associate Professor of Physiology College of Medicine King Saud University INTRODUCTION Diabetic nephropathy (DN) DN is defined as the appearance of persistent clinical albuminuria in an

More information

Summary 255 Research Summary

Summary 255 Research Summary Chapter 10 Summary Nephrolithiasis remains a public health problem around the world, affecting 12% of the adult population. The prevalence and incidence of kidney stones are increasing with global warming,

More information

Hasan Fattah 4/30/2013

Hasan Fattah 4/30/2013 Hasan Fattah 4/30/2013 49 yo hispanic male, ho HIV(CD4 229), currently on HAART, course c/b AIDS, Presents with two days ho fever, SOB, blood tinged sputum, and visible hematuria. ROS: no skin rash, joint

More information

Renal Disease and PK/PD. Anjay Rastogi MD PhD Division of Nephrology

Renal Disease and PK/PD. Anjay Rastogi MD PhD Division of Nephrology Renal Disease and PK/PD Anjay Rastogi MD PhD Division of Nephrology Drugs and Kidneys Kidney is one of the major organ of drug elimination from the human body Renal disease and dialysis alters the pharmacokinetics

More information

Chapter 4. Drug Biotransformation

Chapter 4. Drug Biotransformation Chapter 4 Drug Biotransformation Drug Biotransformation 1 Why is drug biotransformation necessary 2 The role of biotransformation in drug disposition 3 Where do drug biotransformation occur 4 The enzymes

More information

Mouse Models of Diabetic Nephropathy. Mount Sinai / Jefferson / Einstein / Minnesota Erwin Böttinger, PI Kumar Sharma, Co-PI

Mouse Models of Diabetic Nephropathy. Mount Sinai / Jefferson / Einstein / Minnesota Erwin Böttinger, PI Kumar Sharma, Co-PI Mouse Models of Diabetic Nephropathy Mount Sinai / Jefferson / Einstein / Minnesota Erwin Böttinger, PI Kumar Sharma, Co-PI Group Members Mount Sinai: Phenotyping, Molecular Pathology & Validation Erwin

More information

Novel therapeutic approach for kidney fibrosis

Novel therapeutic approach for kidney fibrosis University of Sydney Novel therapeutic approach for kidney fibrosis DAVID HARRIS 30/09/17 Westmead Hospital Cadnapaphornchai CJASN 2014;9:889 Liraglutide: Renal Outcomes Mann JFE et al. N Engl J Med 2017;377:839-848

More information

SLOWING PROGRESSION OF KIDNEY DISEASE. Mark Rosenberg MD University of Minnesota

SLOWING PROGRESSION OF KIDNEY DISEASE. Mark Rosenberg MD University of Minnesota SLOWING PROGRESSION OF KIDNEY DISEASE Mark Rosenberg MD University of Minnesota OUTLINE 1. Epidemiology of progression 2. Therapy to slow progression a. Blood Pressure control b. Renin-angiotensin-aldosterone

More information

number Done by Corrected by Doctor

number Done by Corrected by Doctor number 19 Done by حسام ابو عوض Corrected by وسيم ابو عبيدة Doctor د.نايف 1 P a g e GAGs and Glycoproteins: GAGs: long, unbranched heteropolysaccharides, made from زunits repeating disaccharide [Acidic

More information

Michigan/Chicago unit

Michigan/Chicago unit Michigan/Chicago unit Modifications in Mouse Models to Enhance Nephropathy/Neuropathy- GLUT1 overexpression Increased oxidative stress Increased glucose metabolic flux or alteration in GLUT expression

More information

LIPID METABOLISM. Sri Widia A Jusman Department of Biochemistry & Molecular Biology FMUI

LIPID METABOLISM. Sri Widia A Jusman Department of Biochemistry & Molecular Biology FMUI LIPID METABOLISM Sri Widia A Jusman Department of Biochemistry & Molecular Biology FMUI Lipid metabolism is concerned mainly with fatty acids cholesterol Source of fatty acids from dietary fat de novo

More information

Metabolic Syndrome. DOPE amines COGS 163

Metabolic Syndrome. DOPE amines COGS 163 Metabolic Syndrome DOPE amines COGS 163 Overview - M etabolic Syndrome - General definition and criteria - Importance of diagnosis - Glucose Homeostasis - Type 2 Diabetes Mellitus - Insulin Resistance

More information

Lujain Hamdan. Faisal Nimri

Lujain Hamdan. Faisal Nimri 20 Lujain Hamdan Faisal Nimri...... Sources of NADPH [ The pentose phosphate pathway is the primary source of the NADPH and is the only source in RBC.] Cytosolic conversion of oxaloacetate to pyruvate

More information

Diabetic Nephropathy 2009

Diabetic Nephropathy 2009 Diabetic Nephropathy 2009 Michael T McDermott MD Director, Endocrinology and Diabetes Practice University of Colorado Hospital Michael.mcdermott@ucdenver.edu Diabetic Nephropathy Clinical Stages Hyperfunction

More information

Effects of beraprost sodium on renal function and inflammatory factors of rats with diabetic nephropathy

Effects of beraprost sodium on renal function and inflammatory factors of rats with diabetic nephropathy Effects of beraprost sodium on renal function and inflammatory factors of rats with diabetic nephropathy J. Guan 1,2, L. Long 1, Y.-Q. Chen 1, Y. Yin 1, L. Li 1, C.-X. Zhang 1, L. Deng 1 and L.-H. Tian

More information

Proceedings of the 34th World Small Animal Veterinary Congress WSAVA 2009

Proceedings of the 34th World Small Animal Veterinary Congress WSAVA 2009 www.ivis.org Proceedings of the 34th World Small Animal Veterinary Congress WSAVA 2009 São Paulo, Brazil - 2009 Next WSAVA Congress : Reprinted in IVIS with the permission of the Congress Organizers PROTEINURIA

More information

Glutathione / Thioredoxin Nrf2 & Hyperoxia

Glutathione / Thioredoxin Nrf2 & Hyperoxia Glutathione / Thioredoxin Nrf2 & Hyperoxia Trent E. Tipple, MD Principal Investigator, Center for Perinatal Research The Research Institute at Nationwide Children s Hospital Assistant Professor of Pediatrics,

More information

Diabetic Nephropathy

Diabetic Nephropathy Diabetic Nephropathy Outline Introduction of diabetic nephropathy Manifestations of diabetic nephropathy Staging of diabetic nephropathy Microalbuminuria Diagnosis of diabetic nephropathy Treatment of

More information

Industrial Toxicology

Industrial Toxicology Industrial Toxicology Learning Objectives Know the assumptions of the doseresponse and time-course curves Be able to define and label key points of a curve Know the difference between potency and efficacy

More information

BIOCHEMICHISTRY OF EYE TISSUE. Sri Widia A Jusman Department of Biochemistry & Molecular Biology FMUI

BIOCHEMICHISTRY OF EYE TISSUE. Sri Widia A Jusman Department of Biochemistry & Molecular Biology FMUI BIOCHEMICHISTRY OF EYE TISSUE Sri Widia A Jusman Department of Biochemistry & Molecular Biology FMUI 1 METABOLIC PATHWAYS IN EYE TISSUE Glycolysis ( aerobic & anaerobic) HMP shunt Poliol pathway TCA cycle

More information

β adrenergic blockade, a renal perspective Prof S O McLigeyo

β adrenergic blockade, a renal perspective Prof S O McLigeyo β adrenergic blockade, a renal perspective Prof S O McLigeyo Carvedilol Third generation β blocker (both β 1 and β 2 ) Possesses α 1 adrenergic blocking properties. β: α blocking ratio 7:1 to 3:1 Antioxidant

More information

REVIEW ARTICLE NEWER BIOMARKERS IN EARLY DIABETIC NEPHROPATHY

REVIEW ARTICLE NEWER BIOMARKERS IN EARLY DIABETIC NEPHROPATHY JCD REVIEW ARTICLE NEWER BIOMARKERS IN EARLY DIABETIC NEPHROPATHY SAPTARSHI MUKHOPADHYAY* *FACULTY (DEPARTMENT OF MEDICINE), B R SINGH HOSPITAL (EASTERN RAILWAY), KOLKATA. INTRODUCTION renal disease. It

More information

Mouse Models of Diabetic Nephropathy. Mount Sinai / Jefferson / Einstein / Minnesota Erwin Böttinger, PI Kumar Sharma, Co-PI

Mouse Models of Diabetic Nephropathy. Mount Sinai / Jefferson / Einstein / Minnesota Erwin Böttinger, PI Kumar Sharma, Co-PI Mouse Models of Diabetic Nephropathy Mount Sinai / Jefferson / Einstein / Minnesota Erwin Böttinger, PI Kumar Sharma, Co-PI Group Members Mount Sinai: Phenotyping, Molecular Pathology & Validation Erwin

More information

Drug Dosing in Renal Insufficiency. Coralie Therese D. Dimacali, MD College of Medicine University of the Philippines Manila

Drug Dosing in Renal Insufficiency. Coralie Therese D. Dimacali, MD College of Medicine University of the Philippines Manila Drug Dosing in Renal Insufficiency Coralie Therese D. Dimacali, MD College of Medicine University of the Philippines Manila Declaration of Conflict of Interest For today s lecture on Drug Dosing in Renal

More information

Chronic Calcineurin Inhibitor Nephrotoxicity: Myth or Reality?

Chronic Calcineurin Inhibitor Nephrotoxicity: Myth or Reality? Chronic Calcineurin Inhibitor Nephrotoxicity: Myth or Reality? Aji Djamali, MD Associate Professor of Medicine and Surgery Division Chief Nephrology University of Wisconsin School of Medicine and Public

More information

Structure. Lysosomes are membrane-enclosed organelles. Hydrolytic enzymes. Variable in size & shape need

Structure. Lysosomes are membrane-enclosed organelles. Hydrolytic enzymes. Variable in size & shape need Lysosomes Structure Lysosomes are membrane-enclosed organelles Hydrolytic enzymes Variable in size & shape need Degrade material taken up from outside and inside the cell Variable in size and shape Lysosomal

More information

Electron Transport Chain and Oxidative phosphorylation

Electron Transport Chain and Oxidative phosphorylation Electron Transport Chain and Oxidative phosphorylation So far we have discussed the catabolism involving oxidation of 6 carbons of glucose to CO 2 via glycolysis and CAC without any oxygen molecule directly

More information

AGING KIDNEY IN HIV DISEASE

AGING KIDNEY IN HIV DISEASE AGING KIDNEY IN HIV DISEASE Michael G. Shlipak, MD, MPH Professor of Medicine, Epidemiology and Biostatistics, UCSF Chief, General Internal Medicine, San Francisco VA Medical Center Kidney, Aging and HIV

More information

B. Incorrect! Compounds are made more polar, to increase their excretion.

B. Incorrect! Compounds are made more polar, to increase their excretion. Pharmacology - Problem Drill 04: Biotransformation Question No. 1 of 10 Instructions: (1) Read the problem and answer choices carefully, (2) Work the problems on paper as 1. What is biotransformation?

More information

Principles of Toxicology: The Study of Poisons

Principles of Toxicology: The Study of Poisons Principles of Toxicology: The Study of Poisons Elizabeth Casarez Department of Pharmacology and Toxicology University it of Arizona The study of the adverse effects of a toxicant on living organisms Adverse

More information

Increased oxidative and glyco-oxidative stress has

Increased oxidative and glyco-oxidative stress has Overexpression of Cu 2 /Zn 2 Superoxide Dismutase Protects Against Early Diabetic Glomerular Injury in Transgenic Mice Patricia A. Craven, 1 Mona F. Melhem, 2 Stephen L. Phillips, 3 and Frederick R. DeRubertis

More information

Moh Tarek + Faisal Massad. Tala Saleh ... Naif

Moh Tarek + Faisal Massad. Tala Saleh ... Naif 19 Moh Tarek + Faisal Massad Tala Saleh... Naif Last lecture we ve talked about the main antioxidant system which are the enzymes found in our body, mainly: 1. Glutathione peroxidase 2. Super oxide dismutase(sod)

More information

A. One to three months of age. Anterior Lens (Mean ± SEM) Posterior Lens (Mean ± SEM) Mid Lens (Mean ± SEM) Cornea (Mean ± SEM) Genotype

A. One to three months of age. Anterior Lens (Mean ± SEM) Posterior Lens (Mean ± SEM) Mid Lens (Mean ± SEM) Cornea (Mean ± SEM) Genotype Supplementary Table 1. Location of lens opacification in Aldh1a1(-/-), Aldh3a1(-/-) single and Aldh1a1(-/-)/Aldh3a1(-/-) double knockout mice (DKO) at different ages. A. One to three months of age Genotype

More information

Package Insert. Elkar

Package Insert. Elkar Package Insert Elkar Product Summary 1. Name of the medicinal product Elkar 500 mg tablets 2. Qualitative and quantitative composition Each tablet contains levocarnitine 500 mg. 3. Pharmaceutical form

More information

Ανάπτυξη Βιοτράπεζας για την Ανίχνευση Πρώιμων Βιοδεικτών σε Ασθενείς με Χρόνια Νεφρική Νόσο

Ανάπτυξη Βιοτράπεζας για την Ανίχνευση Πρώιμων Βιοδεικτών σε Ασθενείς με Χρόνια Νεφρική Νόσο Ανάπτυξη Βιοτράπεζας για την Ανίχνευση Πρώιμων Βιοδεικτών σε Ασθενείς με Χρόνια Νεφρική Νόσο ΔΗΜΗΤΡΙΟΣ Σ. ΓΟΥΜΕΝΟΣ Νεφρολογικό και Μεταμοσχευτικό Κέντρο Πανεπιστημιακό Νοσοκομείο Πατρών Causes of chronic

More information

>4000 mg/dl (=20000/(500/100)) >615 mmol/l (=20000/(65*0.5))

>4000 mg/dl (=20000/(500/100)) >615 mmol/l (=20000/(65*0.5)) Supplemental Table 1 Thresholds to define outliers of lab values in screening test for proteinuria Type of screening test Unit Threshold for Outliers References 24 hour urine albumin mg/d >20000 experienced

More information

IVC History, Cancer Research

IVC History, Cancer Research Riordan Clinic IVC Academy 5 IVC History, Cancer Research O (slides 1 40) Riordan Clinic 2018 High Dose Vitamin C Adjunctive Care for Cancer Patients IVC and Cancer Research Overview History & Research

More information

2015 ICDM, 15-17, Jejudob Island, Korea Recent Advances in Diabetic Microvascular Complications. DPP-4 Inhibition and Diabetic Nephropathy

2015 ICDM, 15-17, Jejudob Island, Korea Recent Advances in Diabetic Microvascular Complications. DPP-4 Inhibition and Diabetic Nephropathy 2015 ICDM, 15-17, Jejudob Island, Korea Recent Advances in Diabetic Microvascular Complications DPP-4 Inhibition and Diabetic Nephropathy Daisuke Koya Department of Diabetology & Endocrinology Kanazawa

More information

Therapies for DILI: NAC, Steroids or NRF-2 activators?

Therapies for DILI: NAC, Steroids or NRF-2 activators? Therapies for DILI: NAC, Steroids or NRF-2 activators? William M. Lee, MD Professor of Internal Medicine Meredith Mosle Chair in Liver Diseases UT Southwestern Medical Center at Dallas Drug-Induced Liver

More information

International Journal of Chemistry and Pharmaceutical Sciences

International Journal of Chemistry and Pharmaceutical Sciences International Journal of Chemistry and Pharmaceutical Sciences Journal Home Page: www.pharmaresearchlibrary.com/ijcps Review Article Open Access Astashine Silver Capsules: An Excellent Choice as Anti-Diabetic

More information

Pro-Oxidant Environmental Exposures: Implications of Redox Imbalance in Autism S. Jill James, Ph.D.

Pro-Oxidant Environmental Exposures: Implications of Redox Imbalance in Autism S. Jill James, Ph.D. Pro-Oxidant Environmental Exposures: Implications of Redox Imbalance in Autism S. Jill James, Ph.D. Professor, Department of Pediatrics Director, Autism Metabolic Genomics Laboratory Arkansas Children

More information

Dr. Shiva Nazari Assistant Professor of Pediatric Oncologist & Hematologist Shahid Beheshti Medical Science University Mofid Children s Hospital

Dr. Shiva Nazari Assistant Professor of Pediatric Oncologist & Hematologist Shahid Beheshti Medical Science University Mofid Children s Hospital Dr. Shiva Nazari Assistant Professor of Pediatric Oncologist & Hematologist Shahid Beheshti Medical Science University Mofid Children s Hospital Reduction in the normal red cell survival (120 days) RBC

More information

Macrovascular Disease in Diabetes

Macrovascular Disease in Diabetes Macrovascular Disease in Diabetes William R. Hiatt, MD Professor of Medicine/Cardiology University of Colorado School of Medicine President, CPC Clinical Research Conflicts CPC Clinical Research (University-based

More information

Effective Treatment Strategies to Delay the Progression of Renal Disease in CKD

Effective Treatment Strategies to Delay the Progression of Renal Disease in CKD Effective Treatment Strategies to Delay the Progression of Renal Disease in CKD Csaba P Kovesdy, MD FASN Memphis VA Medical Center, Memphis TN University of Tennessee, Memphis TN Vitamin D Metabolic acidosis

More information

Introduction. Acute sodium overload produces renal tubulointerstitial inflammation in normal rats

Introduction. Acute sodium overload produces renal tubulointerstitial inflammation in normal rats Acute sodium overload produces renal tubulointerstitial inflammation in normal rats MI Roson, et al. Kidney International (2006) Introduction Present by Kanya Bunnan and Wiraporn paebua Tubular sodium

More information

Mechanism of Detoxification

Mechanism of Detoxification Mechanism of Detoxification Prof.Dr. Hedef Dhafir El-Yassin 1 Objectives: 1. To list the detoxification pathways 2. To describe detoxification pathways and phases in the liver, 2 3 4 o Xenobiotics are

More information

Bilirubin and biliverdin protect rodents against diabetic nephropathy by downregulating NAD(P)H oxidase

Bilirubin and biliverdin protect rodents against diabetic nephropathy by downregulating NAD(P)H oxidase http://www.kidney-international.org & 21 International Society of Nephrology Bilirubin and biliverdin protect rodents against diabetic nephropathy by downregulating NAD(P)H oxidase Masakazu Fujii 1, Toyoshi

More information

It the process by which a drug reversibly leaves blood and enter interstitium (extracellular fluid) and/ or cells of tissues.

It the process by which a drug reversibly leaves blood and enter interstitium (extracellular fluid) and/ or cells of tissues. It the process by which a drug reversibly leaves blood and enter interstitium (extracellular fluid) and/ or cells of tissues. Primarily depends on: 1.Regional blood flow. 2.Capillary permeability. 3.Protein

More information

CKDinform: A PCP s Guide to CKD Detection and Delaying Progression

CKDinform: A PCP s Guide to CKD Detection and Delaying Progression CKDinform: A PCP s Guide to CKD Detection and Delaying Progression Learning Objectives Describe suitable screening tools, such as GFR and ACR, for proper utilization in clinical practice related to the

More information

Biochemistry: A Short Course

Biochemistry: A Short Course Tymoczko Berg Stryer Biochemistry: A Short Course Second Edition CHAPTER 20 The Electron-Transport Chain 2013 W. H. Freeman and Company Chapter 20 Outline Oxidative phosphorylation captures the energy

More information

Aging and nutrition 03/11/2012. Why do people age? Oxidative stress and damage

Aging and nutrition 03/11/2012. Why do people age? Oxidative stress and damage Aging and nutrition % of elderly people in Canadian population is increasing more than for other age groups within the elderly age group there is great variability in terms health, metabolism, physical

More information

The 12 th Japan-Korea Diabetic Nephropathy Seminar

The 12 th Japan-Korea Diabetic Nephropathy Seminar FINAL REPORT For Japan-Korea Joint Seminar AREA 1. Humanities and Social Sciences 2. Science/Engineering(Excluding Biology and Medicine) 3. Biology/Medicine 4. Interdisciplinary Study 1. Title of Seminar:

More information

OH-selenomethionine: an efficient source of Se in fattening pigs

OH-selenomethionine: an efficient source of Se in fattening pigs OH-selenomethionine: an efficient source of Se in fattening pigs S. GREEN, K. COPPENS, P.-A. GERAERT Adisseo France SAS and Denkavit BV, Netherlands What are our challenges at the animal level? Pork: Transform

More information

HEMOLYSIS AND JAUNDICE:

HEMOLYSIS AND JAUNDICE: 1 University of Papua New Guinea School of Medicine and Health Sciences Division of Basic Medical Sciences Discipline of Biochemistry and Molecular Biology PBL SEMINAR HEMOLYSIS AND JAUNDICE: An overview

More information

BCH 447. Estimation of Serum Urea

BCH 447. Estimation of Serum Urea BCH 447 Estimation of Serum Urea 1 Objective: Estimation of Blood urea nitrogen (BUN) in serum sample. 2 -Urea: Urea is the highest non-protein nitrogen compound in the blood. Urea is the major excretory

More information

BASELINE CHARACTERISTICS OF THE STUDY POPULATION

BASELINE CHARACTERISTICS OF THE STUDY POPULATION COMPARISON OF TREATING METABOLIC ACIDOSIS IN CKD STAGE 4 HYPERTENSIVE KIDNEY DISEASE WITH FRUITS & VEGETABLES OR SODIUM BICARBONATE This was a 1-year, single-center, prospective, randomized, interventional

More information

BASELINE CHARACTERISTICS OF THE STUDY POPULATION

BASELINE CHARACTERISTICS OF THE STUDY POPULATION Study Summary DAILY ORAL SODIUM BICARBONATE PRESERVES GLOMERULAR FILTRATION RATE BY SLOWING ITS DECLINE IN EARLY HYPERTENSIVE NEPHROPATHY This was a 5-year, single-center, prospective, randomized, placebo-controlled,

More information

Citric acid cycle and respiratory chain. Pavla Balínová

Citric acid cycle and respiratory chain. Pavla Balínová Citric acid cycle and respiratory chain Pavla Balínová Mitochondria Structure of mitochondria: Outer membrane Inner membrane (folded) Matrix space (mtdna, ribosomes, enzymes of CAC, β-oxidation of FA,

More information

Novel function of NADPH oxidase in atherosclerosis. Yun Soo Bae Department of Life Science Ewha Womans University

Novel function of NADPH oxidase in atherosclerosis. Yun Soo Bae Department of Life Science Ewha Womans University Novel function of NADPH oxidase in atherosclerosis Yun Soo Bae Department of Life Science Ewha Womans University Recent understanding of ROS: act as second messengers e e Catalase/peroxidase O 2 H 2 O

More information

HEMOLYSIS & JAUNDICE: An Overview

HEMOLYSIS & JAUNDICE: An Overview HEMOLYSIS & JAUNDICE: An Overview University of Papua New Guinea School of Medicine and Health Sciences Division of Basic Medical Sciences Discipline of Biochemistry and Molecular Biology PBL MBBS III

More information

Reactive oxygen species: Importance for ischemia/reperfusion (injury)

Reactive oxygen species: Importance for ischemia/reperfusion (injury) Physiologisches Institut Reactive oxygen species: Importance for ischemia/reperfusion (injury) Prof. Dr. Rainer Schulz Reactive oxygen species (ROS) in ischemia/reperfusion injury (IRI) ROS GOOD: Endogenous

More information

Metals in Redox Biology C O R Y B O O N E, C E C I L I A H A G E R T, Q I A N G MA R E D O X - C O U R S E

Metals in Redox Biology C O R Y B O O N E, C E C I L I A H A G E R T, Q I A N G MA R E D O X - C O U R S E Metals in Redox Biology C O R Y B O O N E, C E C I L I A H A G E R T, Q I A N G MA R E D O X - C O U R S E 2 0 1 2 Metals Producing ROS M A Q I A N G ROS as a class includes superoxide radical anion (O

More information

Estimation of Serum Creatinine, Urine Creatinine and Creatinine Clearance. BCH472 [Practical] 1

Estimation of Serum Creatinine, Urine Creatinine and Creatinine Clearance. BCH472 [Practical] 1 Estimation of Serum Creatinine, Urine Creatinine and Creatinine Clearance BCH472 [Practical] 1 -Kidney functions: - The kidneys serve three essential functions: 1. They function as filters, removing metabolic

More information

Plasma proteins Quantitatively, proteins are the most important part of the soluble components of the blood plasma.

Plasma proteins Quantitatively, proteins are the most important part of the soluble components of the blood plasma. Plasma proteins 42 Plasma proteins Quantitatively, proteins are the most important part of the soluble components of the blood plasma. concentrations of between 60 and 80 g L 1, they constitute approximately

More information

PRIMARY PHASE 2 ANALYSES FROM CARDINAL: A PHASE 2/3 STUDY OF BARDOXOLONE METHYL IN PATIENTS WITH ALPORT SYNDROME

PRIMARY PHASE 2 ANALYSES FROM CARDINAL: A PHASE 2/3 STUDY OF BARDOXOLONE METHYL IN PATIENTS WITH ALPORT SYNDROME PRIMARY PHASE 2 ANALYSES FROM CARDINAL: A PHASE 2/3 STUDY OF BARDOXOLONE METHYL IN PATIENTS WITH ALPORT SYNDROME 217 American Society of Nephrology Meeting Geoffrey A. Block 1, Pablo E. Pergola 2, Lesley

More information

Figure S1 Generation of γ-gt DTR transgenic mice. (A) Schematic construct of the transgene. (B)

Figure S1 Generation of γ-gt DTR transgenic mice. (A) Schematic construct of the transgene. (B) Figure S1 Generation of γ-gt DTR transgenic mice. (A) Schematic construct of the transgene. (B) PCR identified expected hhb-egf band (left panel) and HA tag band (right) in kidneys of transgenic (TG) mice

More information

Appropriate Laboratory Testing for Toxic Metals

Appropriate Laboratory Testing for Toxic Metals Appropriate Laboratory Testing for Toxic Metals David Quig, PhD Doctor s Data, Inc. Exposure to Toxic Metals Metals Adversely Affect Every Organ System Neurotoxic (ASD, ADHD, PD, Alzhiemers) Cardiovascular

More information

OVERVIEW M ET AB OL IS M OF FR EE FA TT Y AC ID S

OVERVIEW M ET AB OL IS M OF FR EE FA TT Y AC ID S LIPOLYSIS LIPOLYSIS OVERVIEW CATABOLISM OF FREE FATTY ACIDS Nonesterified fatty acids Source:- (a) breakdown of TAG in adipose tissue (b) action of Lipoprotein lipase on plasma TAG Combined with Albumin

More information

Center for Colon Cancer Research at the University of South Carolina. Dr. Franklin G. Berger Director

Center for Colon Cancer Research at the University of South Carolina. Dr. Franklin G. Berger Director Center for Colon Cancer Research at the University of South Carolina Dr. Franklin G. Berger Director WHY COLORECTAL CANCER? **** 4 th highest in cancer incidence and 2 nd highest in mortality. **** Diagnosed

More information

DRIED URINE TESTING-INTEGRATIVE MEDICINE

DRIED URINE TESTING-INTEGRATIVE MEDICINE P: 1300 688 522 E: info@nutripath.com.au A: PO Box 442 Ashburton VIC 3142 TEST PATIENT Sex : D Collected : 00-00-0000 111 ROAD TEST SUBURB AB : 00000000 UR#:0000000 TEST PHYSICIAN DR JOHN DOE 111 CLINIC

More information

New Treatment Options for Diabetic Nephropathy patients. Prof. M. Burnier, Service of Nephrology and Hypertension CHUV, Lausanne, Switzerland

New Treatment Options for Diabetic Nephropathy patients. Prof. M. Burnier, Service of Nephrology and Hypertension CHUV, Lausanne, Switzerland New Treatment Options for Diabetic Nephropathy patients Prof. M. Burnier, Service of Nephrology and Hypertension CHUV, Lausanne, Switzerland Diabetes and nephropathy Diabetic nephropathy is the most common

More information

Convergent and Divergent Mechanisms in Aging and Cancer

Convergent and Divergent Mechanisms in Aging and Cancer Convergent and Divergent Mechanisms in Aging and Cancer Mariana S. De Lorenzo, PhD Department of Cell Biology & Molecular Medicine delorems@umdnj.edu LEARNING OBJECTIVES 1. To identify convergent and divergent

More information

Biological Chemistry of Hydrogen Peroxide

Biological Chemistry of Hydrogen Peroxide Biological Chemistry of Hydrogen Peroxide Christine Winterbourn Department of Pathology University of Otago, Christchurch New Zealand Hydrogen Peroxide Intermediate in reduction of oxygen to water A major

More information

LIST OF FIGURES AND TABLES

LIST OF FIGURES AND TABLES ii LIST OF FIGURES AND TABLES GENERAL INTRODUCTION Fig. 1 Effect of Pb on antioxidant enzymes and cofactors leading to inactivation of enzyme activity Fig. 2 Rationale between Pb exposures among low SES

More information

SALICYLATES. Anthony F. Pizon, M.D. Associate Professor Division Medical Toxicology University of Pittsburgh School of Medicine

SALICYLATES. Anthony F. Pizon, M.D. Associate Professor Division Medical Toxicology University of Pittsburgh School of Medicine SALICYLATES Anthony F. Pizon, M.D. Associate Professor Division Medical Toxicology University of Pittsburgh School of Medicine Overview: Salicylates Found in Willow bark (Salix alba vulgaris) Widely used

More information

23-Jun-15. Albuminuria Renal and Cardiovascular Consequences A history of progress since ,490,000. Kidney Center, UMC Groningen

23-Jun-15. Albuminuria Renal and Cardiovascular Consequences A history of progress since ,490,000. Kidney Center, UMC Groningen Kidney function (egfr in ml/min) Albuminuria (mg/hr) Incidentie ESRD (%) 3-Jun- Number of patients worldwide that receives kidney replacement therapy Albuminuria Renal and Cardiovascular Consequences A

More information

Antioxidant Enzymes. - Superoxide dismutases (SODs) - Catalases - Peroxiredoxins - Glutathione peroxidases

Antioxidant Enzymes. - Superoxide dismutases (SODs) - Catalases - Peroxiredoxins - Glutathione peroxidases Antioxidant Enzymes - Superoxide dismutases (SODs) - Catalases - Peroxiredoxins - Glutathione peroxidases Eva Maria Steiner, Samantha Swenson, Mattias Günther and Xiaoxiao Peng 1 Eva Maria Steiner June

More information

Biologic Oxidation BIOMEDICAL IMPORTAN

Biologic Oxidation BIOMEDICAL IMPORTAN Biologic Oxidation BIOMEDICAL IMPORTAN Chemically, oxidation is defined as the removal of electrons and reduction as the gain of electrons. Thus, oxidation is always accompanied by reduction of an electron

More information

Biomarkers of acrylamide

Biomarkers of acrylamide Biomarkers of acrylamide Jan Alexander Department of Food Safety and Nutrition EFSA Colloquium on Acrylamide, Tabiano, Italy, 22-23 May 2008 Scheme of biomarkers Exposure Internal concentration Internal

More information

AMDCC Progress Report Duke/UNC/Stanford Unit. Program Director Thomas M. Coffman, MD

AMDCC Progress Report Duke/UNC/Stanford Unit. Program Director Thomas M. Coffman, MD AMDCC Progress Report Duke/UNC/Stanford Unit Program Director Thomas M. Coffman, MD Susceptibility Mutation Model Development + ApoE-/- +STZ Kidney Phenotype Screen Vascular & Kidney Phenotype Screen Generate

More information

Long-term Resveratrol Administration Reduces Renal Oxidative Stress and Apoptosis Rate In Experimental Model of Type 2 Diabetes.

Long-term Resveratrol Administration Reduces Renal Oxidative Stress and Apoptosis Rate In Experimental Model of Type 2 Diabetes. Long-term Resveratrol Administration Reduces Renal Oxidative Stress and Apoptosis Rate In Experimental Model of Type 2 Diabetes. Saeed Khamneh 1, Farhad Ghadiri Soufi 2, Fatemeh Afshar 3 1 Department of

More information

Physiopathologie de la Néphropathie Diabétique

Physiopathologie de la Néphropathie Diabétique Physiopathologie de la Néphropathie Diabétique Philippe Rieu Service de Néphrologie et de Transplantation UMR CNRS 6198 Reims Development of diabetic nephropathy 160 14 12 GFR (ml/min) 120 80 40 I II III

More information

Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus

Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus Submit a Manuscript: http://www.wjgnet.com/esps/ Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx DOI: 10.4239/wjd.v6.i3.456 World J Diabetes 2015 April 15; 6(3): 456-480 ISSN 1948-9358 (online) 2015

More information

Renal Clearance. Dr. Eman El Eter

Renal Clearance. Dr. Eman El Eter Renal Clearance Dr. Eman El Eter Concept of clearance Clearance is the volume of plasma that is completely cleared of a substance each minute. Example: Renal clearance of Substance X is defined as the

More information

Morbidity & Mortality from Chronic Kidney Disease

Morbidity & Mortality from Chronic Kidney Disease Morbidity & Mortality from Chronic Kidney Disease Dr. Lam Man-Fai ( 林萬斐醫生 ) Honorary Clinical Assistant Professor MBBS, MRCP, FHKCP, FHKAM, PDipID (HK), FRCP (Edin, Glasg) Hong Kong Renal Registry Report

More information

2. List routes of exposure in the order of most rapid response.

2. List routes of exposure in the order of most rapid response. Practice Test questions: 1. What are the two areas of toxicology that a regulatory toxicologist must integrate in order to determine the "safety" of any chemical? 2. List routes of exposure in the order

More information

Ministry of Health, Labour and Welfare Prevention of Kidney Disease Progression Action Plan

Ministry of Health, Labour and Welfare Prevention of Kidney Disease Progression Action Plan 9 th IKEAJ-CKD International Symposium Ministry of Health, Labour and Welfare Prevention of Kidney Disease Progression Action Plan Division of Nephrology, Hypertension and Endocrinology, Department of

More information

Oxidative stress and antioxidative status in patients with alcoholic liver disease

Oxidative stress and antioxidative status in patients with alcoholic liver disease Biomedical Research 2012; 23 (1): 105-108 Oxidative stress and antioxidative status in patients with alcoholic liver disease Ashok Shinde 1, Jayshree Ganu 2, Pankaja Naik 3, Annasaheb Sawant 4 1 Department

More information

Cellular functions of protein degradation

Cellular functions of protein degradation Protein Degradation Cellular functions of protein degradation 1. Elimination of misfolded and damaged proteins: Environmental toxins, translation errors and genetic mutations can damage proteins. Misfolded

More information

Dr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA

Dr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Dr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Medical Director, Banarsidas Chandiwala Institute of Medical Sciences Chief Consultant, Centre for Diabetes & Lifestyle Diseases,

More information

Lab Values Explained. working at full strength. Other possible causes of an elevated BUN include dehydration and heart failure.

Lab Values Explained. working at full strength. Other possible causes of an elevated BUN include dehydration and heart failure. Patient Education Lab Values Explained Common Tests to Help Diagnose Kidney Disease Lab work, urine samples and other tests may be given as you undergo diagnosis and treatment for renal failure. The test

More information

Lipid Metabolism. Remember fats?? Triacylglycerols - major form of energy storage in animals

Lipid Metabolism. Remember fats?? Triacylglycerols - major form of energy storage in animals Remember fats?? Triacylglycerols - major form of energy storage in animals Your energy reserves: ~0.5% carbs (glycogen + glucose) ~15% protein (muscle, last resort) ~85% fat Why use fat for energy? 1 gram

More information

Protocol GTC : A Randomized, Open Label, Parallel Design Study of Sevelamer Hydrochloride (Renagel ) in Chronic Kidney Disease Patients.

Protocol GTC : A Randomized, Open Label, Parallel Design Study of Sevelamer Hydrochloride (Renagel ) in Chronic Kidney Disease Patients. Protocol GTC-68-208: A Randomized, Open Label, Parallel Design Study of Sevelamer Hydrochloride (Renagel ) in Chronic Kidney Disease Patients. These results are supplied for informational purposes only.

More information

Cardiovascular Implications of Proteinuria

Cardiovascular Implications of Proteinuria Cardiovascular Implications of Proteinuria B. S. Kasinath, MD University of Texas Health Science Center South Texas Veterans Health Care System San Antonio Objectives Mechanisms of albumin handling by

More information

Supplementary Table 1. Criteria for selection of normal control individuals among healthy volunteers

Supplementary Table 1. Criteria for selection of normal control individuals among healthy volunteers Supplementary Table 1. Criteria for selection of normal control individuals among healthy volunteers Medical parameters Cut-off values BMI (kg/m 2 ) 25.0 Waist (cm) (Men and Women) (Men) 85, (Women) 90

More information

Biomarkers of Oxidative Stress and Antioxidant Status in Type 2 Diabetes: Importance in treatment Professor Grace George

Biomarkers of Oxidative Stress and Antioxidant Status in Type 2 Diabetes: Importance in treatment Professor Grace George Division of Medical Biochemistry, Department of Human Biology, Faculty of Health Sciences, Mthatha, South Africa Biomarkers of Oxidative Stress and Antioxidant Status in Type 2 Diabetes: Importance in

More information

PHARMACOLOGY: DEFINITION: CHRONIC BRONCHITIS: CLINICAL USE:

PHARMACOLOGY: DEFINITION: CHRONIC BRONCHITIS: CLINICAL USE: 1 PHARMACOLOGY: HSCH2CH(NHCOCH3)COOH Crystals with a melting point of 109-110 C; used as a mucolytic drug. DEFINITION: Acetylcysteine, also known as N- acetylcysteine (abbreviated NAC), is a pharmacological

More information