NDLI: Metformin overdose causes platelet mitochondrial dysfunction in humans

Content Provider	Springer Nature : BioMed Central
Author	Protti, Alessandro Lecchi, Anna Fortunato, Francesco Artoni, Andrea Greppi, Noemi Vecchio, Sarah Fagiolari, Gigliola Moggio, Maurizio Comi, Giacomo Pietro Mistraletti, Giovanni Lanticina, Barbara Faraldi, Loredana Gattinoni, Luciano
Abstract	Introduction We have recently demonstrated that metformin intoxication causes mitochondrial dysfunction in several porcine tissues, including platelets. The aim of the present work was to clarify whether it also causes mitochondrial dysfunction (and secondary lactate overproduction) in human platelets, in vitro and ex vivo. Methods Human platelets were incubated for 72 hours with saline or increasing doses of metformin (in vitro experiments). Lactate production, respiratory chain complex activities (spectrophotometry), mitochondrial membrane potential (flow-cytometry after staining with JC-1) and oxygen consumption (Clark-type electrode) were then measured. Platelets were also obtained from ten patients with lactic acidosis (arterial pH 6.97 ± 0.18 and lactate 16 ± 7 mmol/L) due to accidental metformin intoxication (serum drug level 32 ± 14 mg/L) and ten healthy volunteers of similar sex and age. Respiratory chain complex activities were measured as above (ex vivo experiments). Results In vitro, metformin dose-dependently increased lactate production (P < 0.001), decreased respiratory chain complex I activity (P = 0.009), mitochondrial membrane potential (P = 0.003) and oxygen consumption (P < 0.001) of human platelets. Ex vivo, platelets taken from intoxicated patients had significantly lower complex I (P = 0.045) and complex IV (P < 0.001) activity compared to controls. Conclusions Depending on dose, metformin can cause mitochondrial dysfunction and lactate overproduction in human platelets in vitro and, possibly, in vivo. Trial registration NCT%2000942123 .
Related Links	https://ccforum.biomedcentral.com/counter/pdf/10.1186/cc11663.pdf
Ending Page	8
Page Count	8
Starting Page	1
File Format	HTM / HTML
ISSN	13648535
DOI	10.1186/cc11663
Journal	Critical Care
Issue Number	5
Volume Number	16
Language	English
Publisher	BioMed Central
Publisher Date	2012-10-03
Access Restriction	Open
Subject Keyword	Intensive Critical Care Medicine Emergency Medicine Metformin Mitochondrial Membrane Potential Lactic Acidosis Human Platelet Respiratory Chain Complex
Content Type	Text
Resource Type	Article
Subject	Critical Care and Intensive Care Medicine
Journal Impact Factor	8.8/2023
5-Year Journal Impact Factor	10.4/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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