Small molecule antioxidants in action Antioxidants Macromolecule – enzymatic, non-enzymatic Small molecule – natural, synthetic Physical abundance – cytoplasmatic (hydrophilic), membrane (lipophilic) When to use antioxidants Therapy of disease (inflammation, ischemia) Support therapy (diabetes mellitus) Prevention (food supplements) Food preservation (nontoxic, healthy) Technical products stabilization (low toxicity) Mechanism of action Prevention of forming RONS – chelating agents Removing RONS – trapping, quenching Decomposition of products of reactions with RONS – repairing mechanisms EDARAVON - Therapy of neurodegenerative disease and stroke Antioxidant efficiency 1. Highest possible reduction potentials between radical and antioxidant 2. Radicals formed from antioxidants must be relatively stable ROS E (mV) Asc∙ – 282 TO∙ 480 O2 ∙ – 940 RO∙ 1600 HO∙ 2310 Antioxidants – hydrogen donors Most commonly contains aromatic cycle with one or more hydroxyl groups Radical is stabilized by electron delocalization Radical can oxidize further Antioxidants – hydrogen donors Lipoperoxidation Deterioration of sensorics properties ● Odor after "rancidity" ● Changes in color and texture ● Loss of consumer interest ● Economic losses Deterioration of nutrition quality ● Essential fat acids Health risks ● GIT, cardiovascular diseases Dietary antioxidants Ascorbic acid (vitamin C) Strong reducing agent High intake – risk of Fenton reaction Hydroxyl radical formation Fe(III) + ascorbate Fe(II) + ascorbate. H2O2 + Fe(II) HO· + OH- + Fe(III) Dietary antioxidants Tocopherols (vitamin E) Dietary antioxidants Tocopherols (vitamin E) Flavonoids– example of action Curcumin – neuroprotective, anti-inflammatory Carnosol – lipoperoxidation reduction Quercetin – colorectal carcinom reduction Resveratrol – antiaging, CVS, CA, diabetes Sofalcone - antiulcerosum, anti-inflammatory Dietary antioxidants Carotenoids Dietary antioxidants Carotenoids – mechanism of action Dietary antioxidants - Flavonoids Dietary antioxidants - Flavonoids Dietary antioxidants - Flavonoids Dietary antioxidants - Flavonoids Dietary antioxidants – Flavonoids Mechanism of action Dietary antioxidants - Stilbens Dietary antioxidants - Stilbens Dietary antioxidants - Stilbens Resveratrol Dietary antioxidants - Curcumin Curcuma longa L. (Zingiberaceae) Dietary antioxidants – Aromatic acids Rosmarinic acid Chlorogenic acid Dietary antioxidants – Nitrogen based antioxidants Caffeine Dietary antioxidants – Chelating agens Formation complexes with metallic ions Prevention of oxidative state changes of metallic ion Sterically shielding metallic ion and lipid radical Dietary antioxidants – Chelating agents Endogenous antioxidants Ubiquinone (coenzyme Q10) Bilirubin Melatonin Lipoic acid Uric acid Melanine Retarders vs. antioxidants Retarders – just slowing oxidation and requires high concentration HO* - reaction rate constant - 109 – 1010 M-1 * s-1 Effective antioxidant 1 * 1013 M-1 * s-1 Impossible in water 1 * 1011 M-1 * s-1 HO∙ no antioxidants just retarders Reaction rate constants SOD 7 x 109 M−1s−1 HO· 1.1 x 1010 M−1s−1 RO· (tert-butyl alkoxyl radical) 1.6 x 109 M−1s−1 ROO· (alkyl peroxyl radical, e.g. CH3OO·) 1-2 x 106 M−1s−1 Cl3COO· 1.8 x 108 M−1s−1 GS· (glutathiyl radical) 6 x 108 M−1s−1 UH·- (Urate radical) 1 x 106 M−1s−1 TO· (Tocopheroxyl radical) 2 x 105 M−1s−1 Asc·- (dismutation) 2 x 105 M−1s−1 CPZ·+ (Clorpromazine radical radical) 1.4 x 109 M−1s−1 Fe(III)EDTA/ Fe(II)EDTA » 1 x 102 M−1s−1 O2·-/HO2· 2.7 x 105 M−1s−1 Thank you