AIM: Because "metformin-associated lactic acidosis" refers to metformin and concurrent pathologies as co-precipitating factors, the respective impact in the outcome of metformin therapy, metformin accumulation, and general diseases should be determined. We therefore constructed a model of sepsis in mice treated with metformin at a dose corresponding to clinical practice, or to accumulation. METHODS: 460 mice were separated in 3 groups: no metformin therapy, a 7-day metformin therapy at 50 mg.kg(-1).day(-1) (MET50) or 500 mg.kg(-1).day(-1) (MET500). Blood was drawn on day 7 in 40 metformin-treated animals for determining metformin concentrations. The 420 other mice were divided in 14 subgroups according to the amount of an intra-peritoneal inoculum of E. coli ranging from 5.103 to 1010 CFU/ml in order to construct a lethal dose curve. The survival rate was assessed at 7, 13, 24, 36, 60 and 120 hours thereafter. RESULTS: Plasma metformin concentrations were 0.26 +/- 0.13 mg/l in MET50, and 4.63 +/- 1.92 mg/l in MET500. The comparative analysis of the survival rates at 120 hours showed no difference of mortality, always occurring for an inoculum amount > 10(8) CFU/ml. Comparing the survival rates from time 0 to 120 hours using Kaplan-Meyer curves and the Logrank test, there was no difference between the different groups. CONCLUSION: Metformin, even at a dose mimicking accumulation, does not aggravate the mortality rate in this model of sepsis. Consequently, metformin can not be considered as toxic in such a condition.
AIM: Because "metformin-associated lactic acidosis" refers to metformin and concurrent pathologies as co-precipitating factors, the respective impact in the outcome of metformin therapy, metformin accumulation, and general diseases should be determined. We therefore constructed a model of sepsis in mice treated with metformin at a dose corresponding to clinical practice, or to accumulation. METHODS: 460 mice were separated in 3 groups: no metformin therapy, a 7-day metformin therapy at 50 mg.kg(-1).day(-1) (MET50) or 500 mg.kg(-1).day(-1) (MET500). Blood was drawn on day 7 in 40 metformin-treated animals for determining metformin concentrations. The 420 other mice were divided in 14 subgroups according to the amount of an intra-peritoneal inoculum of E. coli ranging from 5.103 to 1010 CFU/ml in order to construct a lethal dose curve. The survival rate was assessed at 7, 13, 24, 36, 60 and 120 hours thereafter. RESULTS: Plasma metformin concentrations were 0.26 +/- 0.13 mg/l in MET50, and 4.63 +/- 1.92 mg/l in MET500. The comparative analysis of the survival rates at 120 hours showed no difference of mortality, always occurring for an inoculum amount > 10(8) CFU/ml. Comparing the survival rates from time 0 to 120 hours using Kaplan-Meyer curves and the Logrank test, there was no difference between the different groups. CONCLUSION:Metformin, even at a dose mimicking accumulation, does not aggravate the mortality rate in this model of sepsis. Consequently, metformin can not be considered as toxic in such a condition.
Authors: Konstantin Tsoyi; Hwa Jin Jang; Irina Tsoy Nizamutdinova; Young Min Kim; Young Soo Lee; Hye Jung Kim; Han Geuk Seo; Jae Heun Lee; Ki Churl Chang Journal: Br J Pharmacol Date: 2011-04 Impact factor: 8.739
Authors: Mary Ellen Sanders; Louis M A Akkermans; Dirk Haller; Cathy Hammerman; James Heimbach; Gabriele Hörmannsperger; Geert Huys; Dan D Levy; Femke Lutgendorff; David Mack; Phoukham Phothirath; Gloria Solano-Aguilar; Elaine Vaughan Journal: Gut Microbes Date: 2010-03-04
Authors: Theodora Tzanavari; Aimilia Varela; Stamatis Theocharis; Elpinickie Ninou; Alkistis Kapelouzou; Dennis V Cokkinos; Maria I Kontaridis; Katia P Karalis Journal: Metabolism Date: 2016-07-09 Impact factor: 8.694