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
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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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
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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
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UT code for WoS article
000407199100001
EID of the result in the Scopus database
2-s2.0-85028431346