2023_L8.pdf

Popławski Tomasz Reactive oxygen species 2 3 4 5 6 7 8  The origin of the multicellular Ediacarabiota  The Cambrian explosion  The trends in animal body size  Extinction and diversification events  Driver for evolutionary diversification...

Popławski Tomasz Reactive oxygen species 2 3 4 5 6 7 8  The origin of the multicellular Ediacarabiota  The Cambrian explosion  The trends in animal body size  Extinction and diversification events  Driver for evolutionary diversification 9 10  We metabolize and utilize oxygen to energy production.  The energy is created through mitochondrial oxidative phosphorylation ▪ the reduction of oxygen to water  It leads to the formation of oxygen free radicals. 11  Molecules with one or more unpaired electron(s)  Unstable and extremely reactive molecules  Can oxidize and modify nearby molecules  Oxidized molecules become free radicals themselves 12  Toxic Liver Injury (several examples)  Nutritional Liver Disease (some examples)  Alcoholism  Inflammation  Rheumatoid Arthritis  Atherosclerosis  Some Parasitic Infections  Some Lung Disorders  Photosensitisation  Reperfusion Injury  Tumour Promotion  Carcinogenesis (some examples) 13  CCl 4  Aromatic nitro-compounds  Aromatic amines  Nitrosamines  Hydrazines  Quinones  Adriamycin 14 15 16 17 18 19 20 21 22 23 24 25 26  monoamino oxidase,  a-ketoglutarae dehydrogenase,  glycerol phosphate dehydrogenase  p66shc ▪ upon oxidative stress, p66Shc translocates to mitochondrial intermembrane space, where it associates with cytochrome c. 27 28  The former (superoxide anion ) is an intramitochondrial metabolite and the latter (hydrogen peroxide ) is a cellular metabolite 29 30 31 32 Antioxidant defense system of human 33 The system includes endogenous and exogenous antioxidants, which plays an important role in maintaining the normal physiological function. Antioxidants Function Enzymatic SODs Catalyze the degradation of superoxide anions. Protect cells from oxygen toxicity and lipid peroxidation Catalase Catalyzes the degradation of hydrogen peroxide. Decreases lipid peroxidation Glutathione peroxidases Remove peroxyl radicals from peroxides Decrease lipid peroxidation 34 Nonenzymatic Glutathione Scavenges free radicals to buffer against high levels of ROS Vitamin C Counteracts superoxide, hydrogen peroxide, and hydroxyl radicals and singlet oxygen actions Prevents lipid peroxidation and reduces hydrogen peroxide–induced DNA damage Recycles vitamin E Vitamin E Traps and scavenges superoxide, hydrogen peroxide, and hydroxyl radicals Protects cell membranes from oxidative damage Coenzyme Q-10 Related to low-density lipoproteins Guards cells against peroxidative damage Recycles vitamin E and inhibits its pro-oxidant capacity Albumin, bilirubin, taurine, Do not prevent against actions of ROS or decrease hypotaurine their production Reduce the risk of the development of oxidative stress 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60