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Bioenergetic bypass...
Bioenergetic bypass using cell-permeable succinate, but not methylene blue, attenuates metformin-induced lactate production
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- Piel, Sarah (författare)
- Lund University,Lunds universitet,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Mitochondrial Medicine,Lund University Research Groups,NeuroVive Pharmaceutical AB
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- Ehinger, Johannes K (författare)
- Lund University,Lunds universitet,Öron-, näs- och halssjukdomar, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Otorhinolaryngology (Lund),Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Mitochondrial Medicine,Lund University Research Groups,NeuroVive Pharmaceutical AB
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- Chamkha, Imen (författare)
- Lund University,Lunds universitet,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Mitochondrial Medicine,Lund University Research Groups,NeuroVive Pharmaceutical AB
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- Frostner, Eleonor Åsander (författare)
- Lund University,Lunds universitet,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Mitochondrial Medicine,Lund University Research Groups,NeuroVive Pharmaceutical AB
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- Sjövall, Fredrik (författare)
- Lund University,Lunds universitet,Klinisk neurofysiologi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Clinical Neurophysiology,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Mitochondrial Medicine,Lund University Research Groups,Skåne University Hospital
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- Elmér, Eskil (författare)
- Lund University,Lunds universitet,Klinisk neurofysiologi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Clinical Neurophysiology,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Mitochondrial Medicine,Lund University Research Groups,NeuroVive Pharmaceutical AB
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- Hansson, Magnus J (författare)
- Lund University,Lunds universitet,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Mitochondrial Medicine,Lund University Research Groups,NeuroVive Pharmaceutical AB
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(creator_code:org_t)
- 2018-08-01
- 2018
- Engelska.
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Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 6:1
- Relaterad länk:
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http://dx.doi.org/10... (free)
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visa fler...
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https://icm-experime...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- BACKGROUND: Metformin is the most common pharmacological treatment for type 2 diabetes. It is considered safe but has been associated with the development of lactic acidosis under circumstances where plasma concentrations exceed therapeutic levels. Metformin-induced lactic acidosis has been linked to the drug's toxic effect on mitochondrial function. Current treatment strategies aim to remove the drug and correct for the acidosis. With a mortality of 20%, complementary treatment strategies are needed. In this study, it was investigated whether targeting mitochondria with pharmacological agents that bypass metformin-induced mitochondrial dysfunction can counteract the energetic deficit linked to toxic doses of metformin.METHODS: The redox agent methylene blue and the cell-permeable succinate prodrug NV118 were evaluated by measuring mitochondrial respiration and lactate production of human platelets exposed to metformin and co-treated with either of the two pharmacological bypass agents.RESULTS: The cell-permeable succinate prodrug NV118 increased mitochondrial respiration which was linked to phosphorylation by the ATP-synthase and alleviated the increase in lactate production induced by toxic doses of metformin. The redox agent methylene blue, in contrast, failed to mitigate the metformin-induced changes in mitochondrial respiration and lactate generation.CONCLUSIONS: The cell-permeable succinate prodrug NV118 bypassed the mitochondrial dysfunction and counteracted the energy deficit associated with toxic doses of metformin. If similar effects of NV118 prove translatable to an in vivo effect, this pharmacological strategy presents as a promising complementary treatment for patients with metformin-induced lactic acidosis.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- mitochondria
- metformin
- methylene blue
- lactic acidosis
- coupled respiration
- succinate
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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