Succinate ameliorates mitochondrial oxygen consumption of metformin-intoxicated human platelets
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KeywordsOxygen Public Health Glutamate Final Concentration Cyanide
Metformin intoxication inhibits mitochondrial complex I and oxygen consumption (VO2). Succinate bypasses complex I by donating electrons to complex II. The aim of this study was to clarify whether succinate ameliorates mitochondrial VO2 of metformin-intoxicated human platelets.
Platelet-rich-plasma was incubated for 72 hours with metformin at a final concentration of 0 mg/l (control), 1.66 mg/l (therapeutic dose) or 166 mg/l (toxic dose). Platelet VO2 was then measured with a Clark-type electrode, in the presence of glutamate plus malate (complex I electron donors) (final concentration: 20 mmol/l for both) or succinate (complex II electron donor) (30 mmol/l), before and after adding cyanide (40 mmol/l). Mitochondrial (cyanide-sensitive) and extra-mitochondrial (cyanide-insensitive) VO2 were corrected for platelet count.
Succinate ameliorates (but does not return to normal) mitochondrial VO2 of human platelets incubated with a toxic dose of metformin.
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