Pleiotropic Effects of Biguanides on Mitochondrial Reactive Oxygen Species Production
Joint Authors
Mracek, Tomas
Alán, Lukáš
Drahota, Zdenek
Pecinova, Alena
Kovalcikova, Jana
Kovarova, Nikola
Pecina, Petr
Zima, Michal
Houstek, Josef
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-08-09
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Metformin is widely prescribed as a first-choice antihyperglycemic drug for treatment of type 2 diabetes mellitus, and recent epidemiological studies showed its utility also in cancer therapy.
Although it is in use since the 1970s, its molecular target, either for antihyperglycemic or antineoplastic action, remains elusive.
However, 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 (10−2–10−1 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.
American Psychological Association (APA)
Pecinova, Alena& Drahota, Zdenek& Kovalcikova, Jana& Kovarova, Nikola& Pecina, Petr& Alán, Lukáš…[et al.]. 2017. Pleiotropic Effects of Biguanides on Mitochondrial Reactive Oxygen Species Production. Oxidative Medicine and Cellular Longevity،Vol. 2017, no. 2017, pp.1-11.
https://search.emarefa.net/detail/BIM-1195403
Modern Language Association (MLA)
Pecinova, Alena…[et al.]. Pleiotropic Effects of Biguanides on Mitochondrial Reactive Oxygen Species Production. Oxidative Medicine and Cellular Longevity No. 2017 (2017), pp.1-11.
https://search.emarefa.net/detail/BIM-1195403
American Medical Association (AMA)
Pecinova, Alena& Drahota, Zdenek& Kovalcikova, Jana& Kovarova, Nikola& Pecina, Petr& Alán, Lukáš…[et al.]. Pleiotropic Effects of Biguanides on Mitochondrial Reactive Oxygen Species Production. Oxidative Medicine and Cellular Longevity. 2017. Vol. 2017, no. 2017, pp.1-11.
https://search.emarefa.net/detail/BIM-1195403
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1195403