We are facing a revival of the strategy to counteract obesity and associated metabolic disorders by inducing thermogenesis mediated by mitochondrial uncoupling protein-1 (UCP1). Thus, the main focus is on the adaptive non-shivering thermogenesis occurring both in the typical depots of brown adipose tissue (BAT) and in UCP1-containing cells that could be induced in white adipose tissue (WAT). Because contribution of WAT to resting metabolic rate is relatively small, the possibility to reduce adiposity by enhancing energy expenditure in classical white adipocytes is largely neglected. However, several pieces of evidence support a notion that induction of energy expenditure based on oxidation of fatty acids (FA) in WAT may be beneficial for health, namely: (i) studies in both humans and rodents document negative association between oxidative capacity of mitochondria in WAT and obesity; (ii) pharmacological activation of AMPK in rats as well as cold-acclimation of UCP1-ablated mice results in obesity resistance associated with increased oxidative capacity in WAT; and (iii) combined intervention using long-chain n-3 polyunsaturated FA (omega 3) and mild calorie restriction exerted synergism in the prevention of obesity in mice fed a high-fat diet; this was associated with strong hypolipidemic and insulin-sensitizing effects, as well as prevention of inflammation, and synergistic induction of mitochondrial oxidative phosphorylation (OXPHOS) and FA oxidation, specifically in epididymal WAT. Importantly, these changes occurred without induction of UCP1 and suggested the involvement of: (i) futile substrate cycle in white adipocytes, which is based on lipolysis of intracellular triacylglycerols and re-esterification of FA, in association with the induction of mitochondrial OXPHOS capacity, β-oxidation, and energy expenditure; (ii) endogenous lipid mediators (namely endocannabinoids, eicosanoids, prostanoids, resolvins, and protectins) and their cognate receptors; and (iii) AMP-activated protein kinase in WAT. Quantitatively, the strong induction of FA oxidation in WAT in response to the combined intervention is similar to that observed in the transgenic mice rendered resistant to obesity by ectopic expression of UCP1 in WAT. The induction of UCP1-independent FA oxidation and energy expenditure in WAT in response to the above physiological stimuli could underlie the amelioration of obesity and low-grade WAT inflammation, and it could reduce the release of FA from adipose tissue and counteract harmful consequences of lipid accumulation in other tissues. In this respect, new combination treatments may be designed using naturally occurring micronutrients (e.g. omega 3), reduced calorie intake or pharmaceuticals, exerting synergism in the induction of the mitochondrial OXPHOS capacity and stimulation of lipid catabolism in white adipocytes, and improving metabolic flexibility of WAT. The role of mutual interactions between adipocytes and immune cells contained in WAT in tissue metabolism should be better characterised. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.
- MeSH
- Adipose Tissue, White cytology metabolism MeSH
- Energy Metabolism * MeSH
- Phenotype MeSH
- Ion Channels metabolism MeSH
- Rats MeSH
- Humans MeSH
- Lipid Metabolism * MeSH
- Mitochondrial Proteins metabolism MeSH
- Mitochondria physiology MeSH
- Mice MeSH
- Oxidative Stress MeSH
- Oxidative Phosphorylation * MeSH
- Signal Transduction MeSH
- Adipocytes cytology metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Corneal alkali burns are potentially blinding injuries. Alkali induces oxidative stress in corneas followed by excessive corneal inflammation, neovascularization, and untransparent scar formation. Molecular hydrogen (H2), a potent reactive oxygen species (ROS) scavenger, suppresses oxidative stress and enables corneal healing when applied on the corneal surface. The purpose of this study was to examine whether the H2 pretreatment of healthy corneas evokes a protective effect against corneal alkali-induced oxidative stress. Rabbit eyes were pretreated with a H2 solution or buffer solution, by drops onto the ocular surface, and the corneas were then burned with 0.25 M NaOH. The results obtained with immunohistochemistry and pachymetry showed that in the corneas of H2-pretreated eyes, slight oxidative stress appeared followed by an increased expression of antioxidant enzymes. When these corneas were postburned with alkali, the alkali-induced oxidative stress was suppressed. This was in contrast to postburned buffer-pretreated corneas, where the oxidative stress was strong. These corneas healed with scar formation and neovascularization, whereas corneas of H2-pretreated eyes healed with restoration of transparency in the majority of cases. Corneal neovascularization was strongly suppressed. Our results suggest that the corneal alkali-induced oxidative stress was reduced via the increased antioxidant capacity of corneal cells against reactive oxygen species (ROS). It is further suggested that the ability of H2 to induce the increase in antioxidant cell capacity is important for eye protection against various diseases or external influences associated with ROS production.
- MeSH
- Alkalies toxicity MeSH
- Antioxidants metabolism MeSH
- Burns, Chemical drug therapy metabolism pathology MeSH
- Epithelial Cells drug effects metabolism pathology MeSH
- Wound Healing drug effects MeSH
- Rabbits MeSH
- Disease Models, Animal MeSH
- Corneal Neovascularization prevention & control MeSH
- Oxidative Stress drug effects MeSH
- Eye Burns chemically induced drug therapy metabolism pathology MeSH
- Reactive Oxygen Species metabolism MeSH
- Cornea blood supply drug effects metabolism pathology MeSH
- Hydrogen pharmacology therapeutic use MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Autoři uvádějí vztah mezi produkcí volných radikálů a antioxidační ochranou organismu. Je probírán význam antioxidačni kapacity plazmy a hlavní látky, které se na ní podílejí. V přehledu jsou pak anlioxidanty děleny na endo- a exogenní, membránové a nemembránové, enzymové a ostatní Stručně je probrána funkce hlavních látek s antioxidačním účinkem a jejich význam i strategie použití v terapii a prevenci poškození organismu volnými radikály.
The authors present the connection between the production of free radicals and antioxidative protection of the organism. The importance of antioxidative capacity of plasma and its main components are discussed. In a review antioxidants are divided into endogenous and exogenous, membrane and non-membrane, enzyme and others. The function of key substances with antioxidative properties is briefly reviewed, along with the importance and the treatment strategy for its use in the therapy and prevention of injury caused by free radicals.
Hyperbarická oxygenácia sa okrem iných indikácií používa ako doplnková liečba nehojacich sa diabetických vredov dolných končatín. Zisťovali sme, či sa po hyperbarickej oxygenoterapii zmení biotransformačná funkcia pečene, peroxidácia lipidov a koncentrácia glukózy, celkového cholesterolu a triacylglycerolov u pacientov s diabetes mellitus typu 2. Súbor tvorili pacienti s diabetes mellitus typu 2 liečení inzulínom. Hyperbarická oxygenácia sa aplikovala raz denne, päťkrát za sebou. Stanovili sme biologický polčas antipyrínu ako modelovej látky, ktorá sa biotransformuje v pečeni. Koncentráciu antipyrínu v plazme sme stanovili plynovou chromatografiou. Koncentráciu malóndialdehydu, ako produktu lipoperoxidácie, kvapalinovou chromatografiou. V súbore pacientov boli sledované parametre a priori horšie oproti fyziologickým hodnotám. Po sérii hyperbarickej oxygenácie sa koncentrácia glukózy významne znížila, koncentrácia celkového cholesterolu a triacylglycerolov sa nezmenila. Hyperbarická oxygenácia neovplyvnila biotransformačnú kapacitu pečene a nespôsobila ďalšie zvýšenie oxidačného stresu u pacientov s diabetes mellitus typu 2, liečených inzulínom. Hyperbarická oxygenácia sa v uvedených podmienkach ukázala ako bezpečná.
Besides other indications, hyperbaric oxygen therapy (HBO) is used as a supplementary treatment of unhealed diabetic ulcers of lower extremities. We examined if the liver function of biotransformation, peroxidation of lipids and concentration of glucose, total cholesterol and triacylglycerols in patients with the type II diabetes would change after hyperbaric oxygen therapy. The sample consisted of patients with the type II diabetes treated with insulin. HBO was applied once a day during the five consecutive days. We examined the biological half-life of antipyrine used as a model substance, which is biotransformed in liver. The concentration of antipyrine in serum was determined by gas chromatography. The concentration of malondialdehyde as a product of lipoperoxidation was determined by liquid chromatography. The parameters measured in the sample of patients before the therapy were worse than physiological values. Following the series of HBO, the concentration of glucose significantly dropped, concentration of total cholesterol and triacylglycerols did not change. HBO did not influenced the biotransformation capacity of liver and did not increase further the oxidative stress in patients with the type II diabetes treated with insulin. HBO proved safe under defined conditions.
- MeSH
- Biotransformation physiology MeSH
- Cholesterol blood MeSH
- Diabetes Mellitus, Type 2 therapy MeSH
- Antipyrine administration & dosage blood MeSH
- Hyperbaric Oxygenation methods utilization MeSH
- Liver metabolism MeSH
- Malondialdehyde blood MeSH
- Oxidative Stress MeSH
- Triglycerides blood MeSH
- Publication type
- Review MeSH
V posledních letech je věnována značná pozornost problematice oxidativního stresu ve vztahu k nádorovým onemocněním. Volné kyslíkové radikály o jsou molekuly s jedním nebo více volnými elektrony, které se velmi pohotově vážou s nitrobuněčnými strukturami za poškozování jejich funkce. Mezi hlavní volné radikály (VR) patří superoxidový anion, hydroxylový radikál, singletový kyslík, peroxynitrit, peroxid vodíku atd. Za fyziologických podmínek je v každé buňce stav dynamické rovnováhy, která je udržována odstraňováním nově vznikajících VR a reparací oxidativním stresem poškozených buněčných struktur. Všeobecný konsenzus přijímá významnou roli oxidativního stresu v karcinogenezi. Předpokládá se, že část nádorových onemocnění vzniká při dlouhodobé oxidativní zátěži v prostředí chronického zánětu. Je prokázaný vztah významných zdrojů VR (kouření, alkohol) v etiologii karcinomů hlavy a krku. Kauzalita vztahu oxidativního stresu a rakoviny je podmíněná chronickým poškozováním struktury DNA volnými radikály. V případě nadměrného poškozování DNA organismus nestíhá reparovat pozměněnou DNA, která má pak významný mutagenní potenciál. Autoři v předkládaném sdělení popisují souhrn teoretických poznatků o vzniku, působení oxidativního stresu a ochraně před ním. Dále uvádí přehled hypotéz jeho vztahu ke kancerogenezi.
Potentially causal relationship between oxidative stress and cancer attracted much attention over the past several years since balance between pro-oxidant and antioxidant capacities is supposed to play an important role in cancer development. Reactive oxygen species (ROS) is a term usually reserved to describe group of highly reactive forms of oxygen carrying one or more unpaired electrons. They include superoxide anion, hydrogen peroxide, hydroxyl radical, singlet oxygen, etc. Surplus electrons, unused for generation of proton gradient, can interact with oxygen to produce superoxide. If not neutralized rapidly enough by the action of antioxidative enzymes and non-enzymatic antioxidants, the intracellular structures are damaged by oxidation. Source of ROS evoking oxidative stress is either exogenous or endogenous. The most important exogenous oxidants are ozone and cigarette smoke. Endogenously, numerous inflammatory cells, e.g. eosinophils, alveolar macrophages, etc., release ROS. However, mitochondria, more precisely protein complexes of the mitochondrial respiratory chain, are a dominant source of endogenous ROS. Pro-oxidant and antioxidant capacities in a healthy cell are kept in dynamic equilibrium by neutralizing overproduction of ROS and rebuilding of damaged intracellular structures. Clinical and experimental studies have provided sufficient background supporting an important role of oxidative stress in cancer development. Oxidative stress is related to cancer in multiple ways. First, oxidative stress can mediate oxidative damage to DNA and thereby initially promote carcinogenesis. Second, many malignant cells have an abnormal ability to cope with oxidative stress due to alterations in their antioxidant properties. One of the cancers with strongest link to oxidative damage and oxidative stress is head and neck squamous cell carcinoma since tobacco and alcohol as sources of massive quantities of ROS are clearly identified as etiologic factors of these malignancies. The authors present theoretical background of genesis and effect of oxidative stress in head and neck cancer. Furthermore, hypotheses of its impact on carcinogenesis are discussed.
- MeSH
- Financing, Government MeSH
- Cocarcinogenesis MeSH
- Humans MeSH
- Biomarkers, Tumor MeSH
- Head and Neck Neoplasms etiology metabolism prevention & control MeSH
- Neoplasms etiology genetics prevention & control MeSH
- Oxidative Stress MeSH
- Oxidants metabolism MeSH
- Free Radicals classification adverse effects MeSH
- Check Tag
- Humans MeSH
Pacienti s chronickým onemocněním ledvin jsou vystaveni oxidačnímu stresu (OS), který se podílí na zhoršení zdravotního stavu. Snížená exkreční schopnost ledvin vede k akumulaci látek s prooxidačními vlastnostmi, které poškozují nejen ledviny, ale celý organizmus, včetně kardiovaskulárního systému. Jednotlivé složky antioxidačního systému hrají významnou roli v eliminaci OS. Právě sledování hladin antioxidantů a produktů OS u těchto pacientů a jejich správná interpretace ve vztahu k funkci ledvin a dalších orgánů, může přispět k zefektivnění jejich léčby a zlepšení zdravotního stavu.
Patients with chronic kidney disease are exposed to oxidative stress (OS) that contributes to deterioration of health. Decrease in renal excretory capacity contributes to the accumulation of pro-oxidative substances that are detrimental not only to kidney but to the whole organism including the cardiovascular system. Components of antioxidant system play an important role in the elimination of the OS. The monitoring of antioxidant levels and products of oxidative damage in these patients and the correct interpretation of relationship between these markers and the function of kidney and other organs may contribute to the more effective treatment and health improvement of the patients.
- Keywords
- reaktivní formy kyslíku a dusíku, antioxidanty,
- MeSH
- Antioxidants physiology chemistry MeSH
- Kidney Failure, Chronic MeSH
- Dialysis MeSH
- Enzymes physiology chemistry MeSH
- Financing, Organized MeSH
- Immunosuppressive Agents MeSH
- Humans MeSH
- Nucleic Acids MeSH
- Oxidative Stress physiology MeSH
- Lipid Peroxidation MeSH
- Proteins MeSH
- Reactive Nitrogen Species MeSH
- Reactive Oxygen Species MeSH
- Transplantation MeSH
- Free Radicals MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Pre zachovanie optimálneho zdravia je potrebná optimálna hladina každého antioxidanta. Kombinovaný efekt neenzymatickej ochrany (ferric reducing ability of plasma - FRAP) je indexom schopnosti odolávať oxidačnému poškodeniu. Plazmatické hladiny vitamínov C, E, A, β-karotén ako aj molámy pomer vitamín E/cholesterol a vitamín C/vitamín E sú signifikantne vyššie v alternatívnej nutričnej skupine (vegetariáni) v porovnaní s kontrolnou skupinou tradičnej výživy. Nadprahové hodnoty esenciálnych antioxidantov (z potravy) znamenitú redukované riziko voľnoradikálových ochorení. Priemerné hodnoty vitamínu C, vitamínu E, vitamínu E/cholesterol, vitamínu C/vitamínu E, vitamínu A a β-kuroténu V skupine vegetariánov sú nadprahové s vysokým percentom individuálnych hodnôt nad limitom (92 % vs 42 % - vitamín C, 88 % vs 50 % - vitamín E/cholesterol, 100 % vs 79 % - vitamín C/vitamín E, 75 % vs 38 % - vitamín A, 67 % vs 17 % - β-karotén). V kontrolnej skupine má nadprahovú hodnotu len vitamín C/vitamín E. Typickým rozdielom alternatívneho stravovania v porovnaní s tradičným je vyššia konzumácia ovocia a zeleniny (vyšší príjem vitamínu C a β-karoténu), ďalej konzumácia celozmných produktov, klíčkov, semien a netradičných rastlinných tukov (tiež vyšší príjem vitamínov E a A). Hladiny exogénnych antioxidantov u zdravej populácie s normálnou absorpciou živín sú plne závislé na skladbe potravy. Hodnoty FRAP sú vyrovnané pre obidve sledované skupiny. Podiel aktivity jednotlivých antioxidantov na celkovej hodnote FRAP je vyšší pre vitamín C a vitamín E u vegetariánov a pre kyselinu močovú v kontrolnej skupine. V prípade celkových bielkovín podiel aktivity je rovnaký vo vegetariánskej aj kontrolnej skupine.
Optimal level of each antioxidant is required for maintenance of optimal health. Combined antioxidant effect of nonenzymatic defenses (ferric reducing ability of plasma - FRAP) is useful as index of ability to resist oxidative damage. Plasma values of vitamins C, E, A, β-carotene as well as molar ratios vitamin E/cholesterol and vitamin C/vitamin E are significantly higher in alternative nutrition group (vegetarians) vs. subjects on traditional nutrition (control group). Overthreshold plasma values of essential antioxidants (from food) mean a reduced risk of freeradical diseases. Average values of vitamin C, vitamin E, vitamin E/cholesterol, vitamin C/vitamin E, vitamin A and β-carotene in vegetarian group are overthreshold with high percent of individual values over limit (92 % vs. 42 % - vitamin C, 88 % vs. 50 % - vitamin E/cholesterol, 100 % vs. 79 % - vitamin C/vitamin E, 75 % vs. 38 % - vitamin A, 67 % vs. 17 % - β-carotene). In control group, overthreshold in only ratio vitamin C/vitamin E. A typical difference of alternative nutrition in comparison to traditional nutrition is higher consumption of fruit and vegetables (higher intake of vitamin C and β-carotene), further consumption of whole grain products, sprouts, seeds and nontraditional plant fats (also higher intake of vitamin E and A). Levels of exogenous antioxidants in healthy population with normal nutrient absorption are fully influenced by food composition. The values of FRAP are equal in both investigated groups. Activity contribution of individual antioxidants to total FRAP is higher for vitamins C and E in vegetarian group and for uric acid in control group. In case of total proteins, the activity contribution is similar in vegetarian group as well as in control group.
