With Bonferroni post hoc test was performed on antimycin-corrected data. way ANOVA with Bonferroni post

With Bonferroni post hoc test was performed on antimycin-corrected data. way ANOVA with Bonferroni post hoc test was performed on antimycin-corrected information. ATORVA, ATORVA, atorvastatin; DMSO, dimethyl sulfoxide; ET, electron transport. ns = no significance; p atorvastatin; DMSO, dimethyl sulfoxide; ET, electron transport. ns = no significance; p 0.05; 0.05; p 0.01; p 0.0001. p 0.01; p 0.0001.3. Discussion 3. DiscussionThe primary locating of this study study statins triggered a important reduction of OXPHOS from the principal getting of this really is which is that statins brought on a substantial reduction coupling efficiency, i.e., the respiratorythe respiratory capacity even in the low even in the OXPHOS coupling efficiency, i.e., capacity to produce ATP, to produce ATP, range. The impact variety. The effect a two level-impairment of level-impairment of CDK19 web mitochondrial reslow was BACE1 list mediated through was mediated by means of a two mitochondrial respiration: enhanced uncouplingincreased uncoupling and inhibition of electron transport, mostly through piration: (elevated LEAK state) (increased LEAK state) and inhibition of electron the reduction of NADH-linked respiration. of NADH-linkedeach statin are exclusive and of transport, largely by means of the reduction The properties of respiration. The properties are summarized special and are summarized in Table 1. each statin are in Table 1.Table 1. Summary of the respiratory effects on the studied statins.Effect OXPHOS coupling efficiency reduction ET capacity inhibitionSimvastatin Atorvastatin Cerivastatin YES YES YES YES YES YESInt. J. Mol. Sci. 2021, 22,8 ofTable 1. Summary in the respiratory effects in the studied statins. Effect OXPHOS coupling efficiency reduction ET capacity inhibition NADH-linked ETS inhibition Direct inhibition of NADH-dehydrogenase Succinate-linked ETS inhibition Uncoupling (elevated LEAK respiration) Simvastatin YES YES YES YES YES NO Atorvastatin YES YES YES YES NO YES Cerivastatin YES YES YES NO NO YESIn our study we applied human platelets as a supply of main human mitochondria. As platelets are recognized to depend on OXPHOS they are able to act as a mirror of mitochondrial function in other tissues. The comparable mitochondrial effects of drug-induced toxicity amongst human platelets and HepG2 cells we observed, have been previously shown by Piel et al. [18] confirming the suitability of platelets for the study of drug-induced mitochondrial effects. Our observations are in line with all the pioneering study of Kaufmann et al. [23], which reported that exposure of rat myoblasts to cerivastatin, atorvastatin and simvastatin for 24 h at 100 resulted in cytotoxicity, inhibition of complexes I, III, IV and decreased mitochondrial membrane possible. However, the uncoupling effects of statins appears to be cell type-dependent. In contrast to our data in freshly isolated human platelets, Kaufman et al. [23] reported that cerivastatin, but not atorvastatin or simvastatin elicited uncoupling in rat myoblasts. More lately, Broniarek et al. [24] reported in mitochondria isolated from a stable human endothelial cell line (EA.hy926 derived from human umbilical vein) an uncoupling effect at concentration as much as one hundred and inhibition of respiration for larger concentrations (up to 300 ) for atorvastatin (but not for pravastatin). Exactly the same group additional reported within the very same in vitro experimental model that even lower concentrations of atorvastatin (100 nM) elicited a reduce in each maximal respiration (as result of sup.