ArticleIntensive care medicine experimental2018
Bioenergetic bypass using cell-permeable succinate, but not methylene blue, attenuates metformin-induced lactate production.
Article in Intensive care medicine experimental, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Focally administered succinate improves cerebral metabolism in traumatic brain injury patients with mitochondrial dysfunction.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Trial
- Phenazine Methosulfate Rewires Mitochondrial Redox Circuits to Restore Membrane Potential and ATP Synthesis Under ETC Blockade in Glioblastoma Cells.Antioxidants (Basel, Switzerland) · 2026Article
- The succinate prodrug NV354 prevents brain lesions and late-stage motor dysfunction in mitochondrial complex I deficiency.iScience · 2026Article
- Optical and Microdialysis Monitoring of Succinate Prodrug Treatment in a Rotenone-Induced Model of Mitochondrial Dysfunction in Swine.Metabolites · 2026Article
- Cell-Free DNA as a Biomarker in a Rodent Model of Chlorpyrifos Poisoning Causing Mitochondrial Dysfunction.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2023Article
- Article
- Succinate prodrugs in combination with atropine and pralidoxime protect cerebral mitochondrial function in a rodent model of acute organophosphate poisoning.Scientific reports · 2022Article
- Impairment of Mitochondrial Respiration in Metabolic Diseases: An Overview.International journal of molecular sciences · 2022Review
- Cell-Permeable Succinate Rescues Mitochondrial Respiration in Cellular Models of Amiodarone Toxicity.International journal of molecular sciences · 2021Article
- Article
- Improvement of Platelet Respiration by Cell-Permeable Succinate in Diabetic Patients Treated with Statins.Life (Basel, Switzerland) · 2021Article
- Cell-Permeable Succinate Rescues Mitochondrial Respiration in Cellular Models of Statin Toxicity.International journal of molecular sciences · 2021Article
- αInternational journal of molecular sciences · 2020Article
- Review
- Mitochondrial respiratory chain complex I dysfunction induced by N-methyl carbamate ex vivo can be alleviated with a cell-permeable succinate prodrug.Toxicology in vitro : an international journal published in association with BIBRA · 2020Article
- Prophylaxis of mitochondrial dysfunction caused by cellular decompression from hyperbaric exposure.Mitochondrion · 2020Article
- Cell-permeable succinate prodrugs rescue mitochondrial respiration in cellular models of acute acetaminophen overdose.PloS one · 2020Article
- Mitochondria-Derived Damage-Associated Molecular Patterns in Sepsis: From Bench to Bedside.Oxidative medicine and cellular longevity · 2019Review
- Succinate and the shortcut to the cure of metformin-induced lactic acidosis.Intensive care medicine experimental · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMetformin 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.
methodsThe 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.
resultsThe 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.
conclusionsThe 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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.