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Pleiotropic Effects of Biguanides on Mitochondrial Reactive Oxygen Species Production

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F17%3A00484402" target="_blank" >RIV/67985823:_____/17:00484402 - isvavai.cz</a>

  • Result on the web

    <a href="http://dx.doi.org/10.1155/2017/7038603" target="_blank" >http://dx.doi.org/10.1155/2017/7038603</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1155/2017/7038603" target="_blank" >10.1155/2017/7038603</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Pleiotropic Effects of Biguanides on Mitochondrial Reactive Oxygen Species Production

  • Original language description

    Metformin is widely prescribed as a first-choice antihyperglycemic drug for treatment of type 2 diabetes mellitus, and additionally recent epidemiological studies showed its utility in cancer therapy. Although it is in use since the 1970s, its molecular target, either for antihyperglycemic or antineoplastic action, remains elusive. The body of the research on metformin effect oscillates around mitochondrial metabolism, including the function of oxidative phosphorylation (OXPHOS) apparatus. In this study, we focused on direct inhibitory mechanism of biguanides (metformin and phenformin) on OXPHOS complexes and its functional impact, using the model of isolated brown adipose tissue mitochondria. We demonstrate that biguanides nonspecifically target the activities of all respiratory chain dehydrogenases (mitochondrial NADH, succinate, and glycerophosphate dehydrogenases), but only at very high concentrations (0.01 – 0.1 M) that highly exceed cellular concentrations observed during the treatment. In addition, these concentrations of biguanides also trigger burst of reactive oxygen species production which, in combination with pleiotropic OXPHOS inhibition, can be toxic for the organism. We conclude that the beneficial effect of biguanides should probably be associated with subtler mechanism, different from the generalized inhibition of the respiratory chain.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2017

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Oxidative Medicine and Cellular Longevity

  • ISSN

    1942-0900

  • e-ISSN

  • Volume of the periodical

    2017

  • Issue of the periodical within the volume

    2017

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    11

  • Pages from-to

  • UT code for WoS article

    000407199100001

  • EID of the result in the Scopus database

    2-s2.0-85028431346