Can oxidative stress be considered an illness?

Author: Faliboga Luana, 4th yearCo-author: Orosan Mihaela-Veronica, 4th yearAssociate professor: Croitoru Mircea, University of Medicine and Pharmacy Tîrgu Mureş, Departament of ToxicologyLecturer: Fogarasi Erzsébet, University of Medicine and Pharmacy Tîrgu Mureş, Departament of Toxicology

IntroductionOxidative stress results from an imbalance between the production of ROS and biological systems` ability to detoxify the reactive intermediates or to repair the resulting damages, which can impact all components of the cell, including proteins, lipids and DNA.

Oxygen is a vital element for all the organisms, but also an important element used in the mitochondria to generate energy when both ROS and RNS are formed.

PROBLEMS occur when the electron flow becomes un coupled generating free radicals.

FREE RADICALS AND OTHER REACTIVE SPECIES INVOLVED IN OXIDATIVE STRESS

ONOO-

[ HOOH]

HO OH

Fe(II),Cu(I),Mn(II),Cr(V),Ni(II)

Fe(III),Cu(II),Mn(III),Cr(VI),Ni(III)

Fenton Reaction

2H+

HOOH

O2O2

SODO2

NO

ONOOCO2-

NO2 CO2

CO2

IN THE ORGANISM ARE NUMEROUS ENZYMES WHICH HAVE THE CAPACITY TO FORM REACTIVE SPECIES

NADPH (CYP450) MPO XO NOS LO Dysfunction of mitochondrial respiratory chain

ANTIOXIDANTS IN THE HUMAN BODY VITAMINS (C,A,E)

GLUTATHIONE SOD CAT GPx Glut red thiol-disulfid and transferse peroxiredoxins oxidoreductase

PROXIDANT-ANTIOXIDANT BALANCE IN THE HUMAN BODY

Oxidative stress and metabolic pathologies

Oxidative stress appears when there is an unbalanced process between the formation of reactive species and the levels of antioxidants in the organism.

plays a pathological role in the development of various diseases including diabetes, atherosclerosis or cancer. The hypothesis that oxidative stress plays a significant role in the evolution of metabolic disorders, especially insulin-resistance state, is supported by several studies( where treatments reducing ROS production reverse metabolic alterations, notably through improvement od insulin sensivity or hyperlipidemia).

OXIDATIVE STRESS MARKERS

I. BIOMARKERS OF LIPID PEROXIDATION: MDA level modified proteins in atherosclerosis HNE level permanently formed at physiological conditions but in larger quantities in

neurodegenerative, atherosclerotic and inflammatory lesions Acrolein present in various environmental sources (cigarette smoke) but is increased in

cardiovascular diseases Isoprostanes family of prostaglandins generated by free radicals catalyzed peroxidation of esterified

arachidonic acidII. BIOMARKERS OF PROTEIN OXIDATION (major targets for reactive oxygen species): Carbonylated proteins level Lys, Arg, Pro and Hys are the principle aminoacid residues to form carbonyl derivates 3-nitrotyrosine (NO2-Tyr) Biomarkers derived from Tyr 3-chlorotyrosine (Cl-Tyr) 3-bromotyrosine(Br-Tyr) III. BIOMARKERS OF OXIDATIVE DAMAGE TO DNA 8-hydroxyl-2`-deoxyguanosine 8-oxo-7,8-dihydro-2`-deoxyguanosine 8-hydroxyguanineIV. OTHER BIOMARKERS Glutathion level

THERAPEUTIC STRATEGIES TO REDUCE OXIDATIVE STRESS

Vitamins with antioxidant effects ( vitamin C, A, E) and ω-3 which are used frequently after a heart surgery. When blood and nutrient flow are reduced during the surgery, ischemic diseases can appear. The ischemic period is followed by an over-active metabolic process soon after the blood and nutrient flow is re-established, leading to generation of high quantities of free radicals. This excess of free radicals is proved to have a high impact on the development of reperfusion injuries.

Polyphenols (resveratrol) found in wine, which have a direct antioxidant effect so they form ROS with lower reactivity and they also have the capacity to activate the endogenous antioxidant system and to inhibit ROS generating enzymatic system. New studies have shown their benefit in diabetes.

THE HUMAN DIET CONTAINS A VAST COMPOUNDS THAT POSSES

ANTIOXIDANT ACTIVITIES BUT IS IT ENOUGH??

Nitrones ( NXY-059) is a synthetic substance, tested in vitro and also in vivo (phase 3 clinical trials in cerebral infarction) being an important spin trap for the superoxide anion and hydroxyl radical and also a source of nitric oxide. Studies have shown it`s safety for the human body but the clinical trails failed in spite of the good results reported in vitro. Hence, NXY-059 can represent a new way in treating oxidative stress.

DISEASES ASSOCIATED WITH OXIDATIVE

STRESS Pulmonary diseases

Neurodegenerative

diseases

Cancer

Age-related

pathologies

Cardiovascular

diseases

Metabolic

diseases

(diabetes)

ATHEROSCLEROSIS

Cholesterol(HDL/LDL)

Atherosclerosis(DISEAS)

Treatment(STATINES)

25(OH)-CHOLESTEROL

OXIDATIVE STRESS

It is known that high level of LDL and low level of HDL is one of the cause of atherosclerosis so the cholesterol lowering medication appeared

NEW STUDIES have shown that oxidation of LDL, a result of oxidative stress via lipid peroxidation, is a good biomarker for the atherogenic process

Diabetes

HYPERGYLICEMIA

DIABETES

Antidiabetic medication

HB-A1c

OXIDATIVE STRESSS

High level of glucose in blood leads to hyperglycaemia, dieses known as DIABETES which has a strict medication and diet still the most useful biomarker used nowadays is Hb-A1c, a result of oxidative stress.

Hb-A1c appears physiologically but when the reactive species are higher than normal the plasma contains more than 5% of total haemoglobin.

Conclusions

There are a lot of biomarkers which show us that oxidative stress can be the key to prevent and to treat a lot of disease if it would be classified as an ILLNESS

Oxidative stress is the key in many pathological processes which could be avoided if the medication for this purpose would be studied

We consider that future design of molecules that will further promote ROS decrease might reveal particular interest

Having all these, we consider that OXIDATIVE STRESS should be considered an illness

THANK YOU FOR YOUR ATTENTION!