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 h with saline or increasing dose 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 00942123

Metformin overdose causes platelet mitochondrial dysfunction in humans / A. Protti, A. Lecchi, F. Fortunato, A. Artoni, N. Greppi, S. Vecchio, G. Fagiolari, M. Moggio, G.P. Comi, G. Mistraletti, B. Lanticina, L. Faraldi, L. Gattinoni. - In: CRITICAL CARE. - ISSN 1466-609X. - 16:5(2012 Oct 03), pp. R180.1-R180.9.

Metformin overdose causes platelet mitochondrial dysfunction in humans

A. Protti
Primo
;
F. Fortunato;G.P. Comi;G. Mistraletti;L. Gattinoni
Ultimo
2012

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 h with saline or increasing dose 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 00942123
Settore MED/41 - Anestesiologia
3-ott-2012
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/209093
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