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Once inside the cell, metformins positive charge leads to its sequestration within the negatively charged mitochondrial matrix, where it can reach concentrations up to 1,000-fold higher than in the extracellular space ( The cardioprotective effects of metformin are both dose-dependent and tissue-specific (Table 2)

Curr Cancer Drug Targ 3:219236 Chen ML et al (2016) Resveratrol attenuates trimethylamine- N -oxide (TMAO)-induced atherosclerosis by regulating TMAO synthesis and bile acid metabolism via remodeling of the gut microbiota

Park SB, Kwok JB, Asher R, Lee CK, Beale P, Selle F, Friedlander M (2017) Clinical and genetic predictors of paclitaxel neurotoxicity based on patient- versus clinicianreported incidence and severity of neurotoxicity in the ICON7 trial