BIOMARKERS AND TOXICITY MECHANISMS 07 Mechanisms Oxidative stress

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BIOMARKERS AND TOXICITY MECHANISMS 07 – Mechanisms Oxidative stress Luděk Bláha, PřF MU, RECETOX

BIOMARKERS AND TOXICITY MECHANISMS 07 – Mechanisms Oxidative stress Luděk Bláha, PřF MU, RECETOX www. recetox. cz

Importance of redox (oxido-reduction) homeostasis Traditional view – “too much oxidants” is bad Prooxidants

Importance of redox (oxido-reduction) homeostasis Traditional view – “too much oxidants” is bad Prooxidants (Oxidative stress) damage to macromolecules death

Importance of redox (oxido-reduction) homeostasis Modified view (2014) – “too much of anything is

Importance of redox (oxido-reduction) homeostasis Modified view (2014) – “too much of anything is bad” http: //www. nature. com/nrm/journal/v 15/n 6/full/nrm 3801. html

Importance of redox (oxido-reduction) homeostasis • Redox homeostasis – natural homeostatic levels of prooxidants

Importance of redox (oxido-reduction) homeostasis • Redox homeostasis – natural homeostatic levels of prooxidants and antioxidants – keeping cell metabolism and signalling balanced • Disruptions of homeostasis depletion of oxygen • Change in metabolism, acidosis in tissues, signalling (e. g. TUMORS) • Less studied – new field – REDOX SIGNALLING overproduction of prooxidants = oxidative stress • GENERAL MECHANISM OF TOXICITY AND AGING

Pro oxidants • Oxygen (O 2) – principal molecule in living organisms • –

Pro oxidants • Oxygen (O 2) – principal molecule in living organisms • – highly reactive molecule • • terminal acceptor of electones) Formation of reactive derivatives ROS toxicity Other reactive molecules and ROS sources – (details follow) • • • production in mitochondria (byproducts of metabolism) redox-cycling (quinones of xenobiotics) Fenton-reaction (metals) oxidations mediated via MFOs (CYPs) depletion of antioxidants (reactive molecules)

Key Reactive Oxygen Species (ROS) SOD = Superoxide dismutase

Key Reactive Oxygen Species (ROS) SOD = Superoxide dismutase

TERMS, NAMES, REACTIONS Fenton reaction (from organic chemistry classes) Fe 3+/2+ But also OTHER

TERMS, NAMES, REACTIONS Fenton reaction (from organic chemistry classes) Fe 3+/2+ But also OTHER METALS (!)

Reactivity of ROS (short rate instability = reactivity)

Reactivity of ROS (short rate instability = reactivity)

Mitochondria Superoxide production in oxidative respiration

Mitochondria Superoxide production in oxidative respiration

Redox cycling compounds and ROS production Toxicity = Interference with “xeno”quinones and similar compounds

Redox cycling compounds and ROS production Toxicity = Interference with “xeno”quinones and similar compounds Example 1 – Ba. P quinone Natural cycling quinone semiquinone Example 2 – Paraquate pesticide

Metals and impacts on redox homeostasis (* direct ROS production / * binding to

Metals and impacts on redox homeostasis (* direct ROS production / * binding to proteins) , Cr + H 2 O 2 (Fenton reaction)

CYP 450 as ROS source (example CYP 2 E 1, MEOS – microsomal ethanol

CYP 450 as ROS source (example CYP 2 E 1, MEOS – microsomal ethanol oxidising system)

Antioxidant responses 1 - enzymatic

Antioxidant responses 1 - enzymatic

Antioxidant responses 2 – GSH

Antioxidant responses 2 – GSH

Antioxidant responses 2 – dietary antioxidants Carotenoids Ascorbate Flavonoids

Antioxidant responses 2 – dietary antioxidants Carotenoids Ascorbate Flavonoids

EFFECTS Enzymes & DNA Other lectures Lipid peroxidation Following slide

EFFECTS Enzymes & DNA Other lectures Lipid peroxidation Following slide

Lipid peroxidation = radical reaction fast propagation MDA as a biomarker

Lipid peroxidation = radical reaction fast propagation MDA as a biomarker

Biomarkers of oxidative damage (will be discussed later)

Biomarkers of oxidative damage (will be discussed later)

Health effects of oxidative stress … multiple e. g. acute coronary syndrome (ACS) myocardial

Health effects of oxidative stress … multiple e. g. acute coronary syndrome (ACS) myocardial infarction

Oxidative stress Oxidative Stress Reactive oxygen species ROSOxidative stress Oxidative Stress Reactive oxygen species ROS
Assessment of Oxidative Stress Oxidative stress involves inAssessment of Oxidative Stress Oxidative stress involves in
BIOMARKERS AND TOXICITY MECHANISMS 04 Mechanisms membranes LudkBIOMARKERS AND TOXICITY MECHANISMS 04 Mechanisms membranes Ludk
BIOMARKERS AND TOXICITY MECHANISMS 03 Mechanisms proteins partBIOMARKERS AND TOXICITY MECHANISMS 03 Mechanisms proteins part
BIOMARKERS AND TOXICITY MECHANISMS 06 Mechanisms Metabolism DetoxificationBIOMARKERS AND TOXICITY MECHANISMS 06 Mechanisms Metabolism Detoxification
BIOMARKERS AND TOXICITY MECHANISMS 05 Mechanisms DNA LudkBIOMARKERS AND TOXICITY MECHANISMS 05 Mechanisms DNA Ludk
BIOMARKERS AND TOXICITY MECHANISMS 02 MECHANISMS OVERVIEW LudkBIOMARKERS AND TOXICITY MECHANISMS 02 MECHANISMS OVERVIEW Ludk
Mechanisms of toxicity Mechanisms of toxicity l lMechanisms of toxicity Mechanisms of toxicity l l
Oxidative Stress and Repair Oxidative DNA modifications FaiezOxidative Stress and Repair Oxidative DNA modifications Faiez
BIOMARKERS AND TOXICITY MECHANISMS 01 INTRODUCTION Ludk BlhaBIOMARKERS AND TOXICITY MECHANISMS 01 INTRODUCTION Ludk Blha
Biomarkers and mechanisms of toxicity Course summary 1Biomarkers and mechanisms of toxicity Course summary 1
Biomarkers and mechanisms of toxicity Course summary 1Biomarkers and mechanisms of toxicity Course summary 1
BIOMARKERS AND TOXICITY MECHANISMS 01 INTRODUCTION Ludk BlhaBIOMARKERS AND TOXICITY MECHANISMS 01 INTRODUCTION Ludk Blha
STRESS AND STRESS DISORDERS Stress and stress disordersSTRESS AND STRESS DISORDERS Stress and stress disorders
Mechanisms of toxicity overview What is the toxicityMechanisms of toxicity overview What is the toxicity
MECHANISMS OF TOXICITY ACUTE TOXICITY LD 50 lethalMECHANISMS OF TOXICITY ACUTE TOXICITY LD 50 lethal
Mechanisms of toxicity overview What is the toxicityMechanisms of toxicity overview What is the toxicity
Oxidative Decarboxylation and Krebs Cycle Objectives Oxidative DecarboxylationOxidative Decarboxylation and Krebs Cycle Objectives Oxidative Decarboxylation
Oxidative Decarboxylation and Krebs Cycle Objectives Oxidative DecarboxylationOxidative Decarboxylation and Krebs Cycle Objectives Oxidative Decarboxylation
Oxidative Damage of DNA Oxidative damage results fromOxidative Damage of DNA Oxidative damage results from
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Oxidative Coupling Scott Dufour Oxidative coupling of aromaticOxidative Coupling Scott Dufour Oxidative coupling of aromatic
glyoxylate cycle Oxidative phosphorylation Oxidative phosphorylation Electrotransfer reactionglyoxylate cycle Oxidative phosphorylation Oxidative phosphorylation Electrotransfer reaction
OXIDATIVE PHOSPHORYLATION MITOCHONDRIA OXIDATIVE PHOSPHORYLATION acceptors electron nicotinamideOXIDATIVE PHOSPHORYLATION MITOCHONDRIA OXIDATIVE PHOSPHORYLATION acceptors electron nicotinamide
LECTURE 16 OXIDATIVE ADDITION OXIDATIVE ADDITION We haveLECTURE 16 OXIDATIVE ADDITION OXIDATIVE ADDITION We have
Thymoquinone attenuates cisplatin induced toxicity and oxidative damageThymoquinone attenuates cisplatin induced toxicity and oxidative damage
MERCURY TOXICITY IN FISH EYES DISCLOSED BY OXIDATIVEMERCURY TOXICITY IN FISH EYES DISCLOSED BY OXIDATIVE
Mechanisms of toxicity mirka rovenskalfmotol cuni cz MechanismsMechanisms of toxicity mirka rovenskalfmotol cuni cz Mechanisms
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Toxicity and Human Health Inneke Hantoro Toxicity isToxicity and Human Health Inneke Hantoro Toxicity is
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Mechanismy toxicity mirka rovenskalfmotol cuni cz Mechanismy toxicityMechanismy toxicity mirka rovenskalfmotol cuni cz Mechanismy toxicity
Hlavn mechanismy toxicity cizorodch ltek HLAVN MECHANISMY TOXICITYHlavn mechanismy toxicity cizorodch ltek HLAVN MECHANISMY TOXICITY
Tylenol Toxicity Kelly Kasteel 1 OBJECTIVES Tylenol toxicityTylenol Toxicity Kelly Kasteel 1 OBJECTIVES Tylenol toxicity
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Managing Stress and Change Stress and Change StressManaging Stress and Change Stress and Change Stress
Stress Analysis Mechanics Stress and strain Stress andStress Analysis Mechanics Stress and strain Stress and
Stress Motivation Theories and Emotional Responses STRESS STRESSStress Motivation Theories and Emotional Responses STRESS STRESS
Stress and Stress Management STRESS SURVEY How WellStress and Stress Management STRESS SURVEY How Well
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