Metformin overdose, but not lactic acidosis per se, inhibits oxygen consumption in pigs

Critical Care

Volumn 16, Issue 3, 2012, Pages

  Protti, Alessandro ^a   Fortunato, Francesco ^a   Monti, Massimo ^a   Vecchio, Sarah ^b   Gatti, Stefano ^a   Comi, Giacomo P ^a   Giuseppe, Rachele D ^a   Gattinoni, Luciano ^a  

^a UNIVERSITY OF MILAN   (Italy)

^b Servizio di Psicologia Fondazione Salvatore Maugeri   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CITRATE SYNTHASE; CYTOCHROME C OXIDASE; LACTIC ACID; METFORMIN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); SUCCINATE DEHYDROGENASE (UBIQUINONE); UBIQUINOL CYTOCHROME C REDUCTASE; ANTIDIABETIC AGENT;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTERIAL PH; ARTICLE; ARTIFICIAL VENTILATION; CONTROLLED STUDY; DRUG INTOXICATION; ENZYME ACTIVITY; EXPERIMENTAL PIG; HEART; HEART OUTPUT; KIDNEY; LACTIC ACIDOSIS; LIVER; NONHUMAN; OXYGEN CONSUMPTION; PRIORITY JOURNAL; SEDATION; SKELETAL MUSCLE; SPECTROPHOTOMETRY; THERMODILUTION; THROMBOCYTE; ANIMAL; DRUG EFFECTS; DRUG OVERDOSE; INTRAVENOUS DRUG ADMINISTRATION; METABOLISM; OXIDATIVE STRESS; PHYSIOLOGY; PIG;

ACIDOSIS, LACTIC; ANIMALS; DRUG OVERDOSE; HYPOGLYCEMIC AGENTS; INFUSIONS, INTRAVENOUS; METFORMIN; OXIDATIVE STRESS; OXYGEN CONSUMPTION; SWINE;

EID: 84860642779     PISSN: 13648535     EISSN: 1466609X     Source Type: Journal    
DOI: 10.1186/cc11332     Document Type: Article

References (41)

1. Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B, , . American Diabetes Association, European Association for the Study of Diabetes Medical management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 2009, 52:17-30. 10.1007/s00125-008-1157-y, 18941734, American Diabetes Association, European Association for the Study of Diabetes.
2. Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev 2010, 4:CD002967.
3. Peters N, Jay N, Barraud D, Cravoisy A, Nace L, Bollaert PE, Gibot S. Metformin-associated lactic acidosis in an intensive care unit. Crit Care 2008, 12:R149. 10.1186/cc7137, 2646313, 19036140.
4. Seidowsky A, Nseir S, Houdret N, Fourrier F. Metformin-associated lactic acidosis: a prognostic and therapeutic study. Crit Care Med 2009, 37:2191-2196. 10.1097/CCM.0b013e3181a02490, 19487945.
5. Friesecke S, Abel P, Roser M, Felix SB, Runge S. Outcome of severe lactic acidosis associated with metformin accumulation. Crit Care 2010, 14:R226. 10.1186/cc9376, 3220003, 21171991.
6. Lalau JD, Race JM. Lactic acidosis in metformin therapy: searching for a link with metformin in reports of 'metformin-associated lactic acidosis'. Diabetes Obes Metab 2001, 3:195-201. 10.1046/j.1463-1326.2001.00128.x, 11412284.
7. Protti A, Russo R, Tagliabue P, Vecchio S, Singer M, Rudiger A, Foti G, Rossi A, Mistraletti G, Gattinoni L. Oxygen consumption is depressed in patients with lactic acidosis due to biguanide intoxication. Crit Care 2010, 14:R22. 10.1186/cc8885, 2875537, 20170489.
8. Stacpoole PW. Metformin and lactic acidosis: guilt by association?. Diabetes Care 1998, 21:1587-1588. 10.2337/diacare.21.10.1587, 9773715.
9. Wang DS, Kusuhara H, Kato Y, Jonker JW, Schinkel AH, Sugiyama Y. Involvement of organic cation transporter 1 in the lactic acidosis caused by metformin. Mol Pharmacol 2003, 63:844-848. 10.1124/mol.63.4.844, 12644585.
10. Wang DS, Kusuhara H, Kato Y, Jonker JW, Schinkel AH, Sugiyama Y. Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin. J Pharmacol Exp Ther 2002, 302:510-515. 10.1124/jpet.102.034140, 12130709.
11. El-Mir MY, Nogueira V, Fontaine E, Avéret N, Rigoulet M, Leverve X. Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem 2000, 275:223-228. 10.1074/jbc.275.1.223, 10617608.
12. Owen MR, Doran E, Halestrap AP. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J 2000, 348:607-614. 10.1042/0264-6021:3480607, 1221104, 10839993.
13. Dykens JA, Jamieson J, Marroquin L, Nadanaciva S, Billis PA, Will Y. Biguanide-induced mitochondrial dysfunction yields increased lactate production and cytotoxicity of aerobically-poised HepG2 cells and human hepatocytes in vitro. Toxicol Appl Pharmacol 2008, 233:203-210. 10.1016/j.taap.2008.08.013, 18817800.
14. Radziuk J, Zhang Z, Wiernsperger N, Pye S. Effects of metformin on lactate uptake and gluconeogenesis in the perfused rat liver. Diabetes 1997, 46:1406-1413. 10.2337/diabetes.46.9.1406, 9287039.
15. Bailey CJ, Wilcock C, Scarpello JH. Metformin and the intestine. Diabetologia 2008, 51:1552-1553. 10.1007/s00125-008-1053-5, 18528677.
16. Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council Guide for the care and use of laboratory animals 1996, Washington, Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council.
17. Ragan CI, Wilson MT, Darley-Usmar VM, Lowe PN. Subfractionation of mitochondria and isolation of the proteins of oxidative phosphorylation. Mitochondria: a practical approach 1987, 79-112. Oxford: IRL Press, Darley-Usmar VM, Rickwood D, Wilson MT.
18. Campise M, Bamonti F, Novembrino C, Ippolito S, Tarantino A, Cornelli U, Lonati S, Cesana BM, Ponticelli C. Oxidative stress in kidney transplant patients. Transplantation 2003, 76:1474-8. 10.1097/01.TP.0000090344.61975.F0, 14657689.
19. Conover WJ, Iman RL. Rank transformations as a bridge between parametric and non-parametric statistics. American Statistician 1981, 35:124-129.
20. Cohen PJ. The metabolic function of oxygen and biochemical lesions of hypoxia. Anesthesiology 1972, 37:148-177. 10.1097/00000542-197208000-00007, 4557886.
21. Ronco JJ, Fenwick JC, Tweeddale MG, Wiggs BR, Phang PT, Cooper DJ, Cunningham KF, Russell JA, Walley KR. Identification of the critical oxygen delivery for anaerobic metabolism in critically ill septic and non septic humans. JAMA 1993, 270:1724-1730. 10.1001/jama.1993.03510140084034, 8411504.
22. Brooks GA. Cell-cell and intracellular lactate shuttles. J Physiol 2009, 587:5591-5600. 10.1113/jphysiol.2009.178350, 2805372, 19805739.
23. James JH, Luchette FA, McCarter FD, Fischer JE. Lactate is an unreliable indicator of tissue hypoxia in injury or sepsis. Lancet 1999, 354:505-508. 10.1016/S0140-6736(98)91132-1, 10465191.
24. Levy B, Gibot S, Franck P, Cravoisy A, Bollaert PE. Relation between muscle Na+K+ ATPase activity and raised lactate concentrations in septic shock: a prospective study. Lancet 2005, 365:871-875. 10.1016/S0140-6736(05)71045-X, 15752531.
25. Peddy SB, Rigby MR, Shaffner DH. Acute cyanide poisoning. Pediatr Crit Care Med 2006, 7:79-82. 10.1097/01.PCC.0000192508.92993.D1, 16395080.
26. Wilcock C, Bailey CJ. Accumulation of metformin by tissues of the normal and diabetic mouse. Xenobiotica 1994, 24:49-57. 10.3109/00498259409043220, 8165821.
27. Brunmair B, Staniek K, Gras F, Scharf N, Althaym A, Clara R, Roden M, Gnaiger E, Nohl H, Waldhäusl W, Fürnsinn C. Thiazolidinediones, like metformin, inhibit respiratory complex I: a common mechanism contributing to their antidiabetic actions?. Diabetes 2004, 53:1052-1059. 10.2337/diabetes.53.4.1052, 15047621.
28. El-Mir MY, Detaille D, R-Villanueva G, Delgado-Esteban M, Guigas B, Attia S, Fontaine E, Almeida A, Leverve X. Neuroprotective role of antidiabetic drug metformin against apoptotic cell death in primary cortical neurons. J Mol Neurosci 2008, 34:77-87. 10.1007/s12031-007-9002-1, 18040888.
29. Morales AI, Detaille D, Prieto M, Puente A, Briones E, Arévalo M, Leverve X, López-Novoa JM, El-Mir MY. Metformin prevents experimental gentamicin-induced nephropathy by a mitochondria-dependent pathway. Kidney Int 2010, 77:861-869. 10.1038/ki.2010.11, 20164825.
30. Detaille D, Guigas B, Chauvin C, Batandier C, Fontaine E, Wiernsperger N, Leverve X. Metformin prevents high-glucose-induced endothelial cell death through a mitochondrial permeability transition-dependent process. Diabetes 2005, 54:2179-2187. 10.2337/diabetes.54.7.2179, 15983220.
31. Zmijewski JW, Lorne E, Zhao X, Tsuruta Y, Sha Y, Liu G, Siegal GP, Abraham E. Mitochondrial respiratory complex I regulates neutrophil activation and severity of lung injury. Am J Respir Crit Care Med 2008, 178:168-179. 10.1164/rccm.200710-1602OC, 2453511, 18436790.
32. Hinke SA, Martens GA, Cai Y, Finsi J, Heimberg H, Pipeleers D, Van de Casteele M. Methyl succinate antagonises biguanide-induced AMPK-activation and death of pancreatic beta-cells through restoration of mitochondrial electron transfer. Br J Pharmacol 2007, 150:1031-1043. 2013909, 17339833.
33. Huckabee WE. Relationships of pyruvate and lactate during anaerobic metabolism. I. Effects of infusion of pyruvate or glucose and of hyperventilation. J Clin Invest 1958, 37:244-254. 10.1172/JCI103603, 293081, 13513755.
34. Suwa M, Egashira T, Nakano H, Sasaki H, Kumagai S. Metformin increases the PGC-1alpha protein and oxidative enzyme activities possibly via AMPK phosphorylation in skeletal muscle in vivo. J Appl Physiol 2006, 101:1685-1692.
35. Nisoli E, Clementi E, Paolucci C, Cozzi V, Tonello C, Sciorati C, Bracale R, Valerio A, Francolini M, Moncada S, Carruba MO. Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science 2003, 299:896-899. 10.1126/science.1079368, 12574632.
36. Clementi E, Brown GC, Feelisch M, Moncada S. Persistent inhibition of cell respiration by nitric oxide: crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione. Proc Natl Acad Sci USA 1998, 95:7631-7636. 10.1073/pnas.95.13.7631, 22706, 9636201.
37. Zou MH, Kirkpatrick SS, Davis BJ, Nelson JS, Wiles WG, Schlattner U, Neumann D, Brownlee M, Freeman MB, Goldman MH. Activation of the AMP-activated protein kinase by the anti-diabetic drug metformin in vivo. Role of mitochondrial reactive nitrogen species. J Biol Chem 2004, 279:43940-51. 10.1074/jbc.M404421200, 15265871.
38. Castro L, Demicheli V, Tórtora V, Radi R. Mitochondrial protein tyrosine nitration. Free Radic Res 2011, 45:37-52. 10.3109/10715762.2010.516254, 20942571.
39. Ensinger H, Weichel T, Lindner KH, Grünert A, Ahnefeld FW. Effects of norepinephrine, epinephrine, and dopamine infusions on oxygen consumption in volunteers. Crit Care Med 1993, 21:1502-1508. 10.1097/00003246-199310000-00018, 8403959.
40. Porta F, Bracht H, Weikert C, Beck M, Takala J, Brandt S, Hiltebrand LB, Jakob SM. Effects of endotoxin and catecholamines on hepatic mitochondrial respiration. Inflammation 2009, 32:315-321. 10.1007/s10753-009-9138-y, 19603262.
41. Vuda M, Brander L, Schröeder R, Jakob SM, Takala J, Djafarzadeh S. Effects of catecholamines on hepatic and skeletal muscle mitochondrial respiration after prolonged exposure to faecal peritonitis in pigs. Innate Immun 2012, 18:217-230. 10.1177/1753425911398279, 21525237.