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Fig. 1 | Intensive Care Medicine Experimental

Fig. 1

From: Bioenergetic bypass using cell-permeable succinate, but not methylene blue, attenuates metformin-induced lactate production

Fig. 1

Dose-response of methylene blue and NV118 on oxygen consumption in rotenone-intoxicated human platelets. Respiration was measured in human platelets with complex I inhibition induced by rotenone (2 μM). The potential of the pharmacological bypass strategies methylene blue (a black square) and the cell-permeable succinate prodrug NV118 (b black triangle) to increase rotenone-inhibited respiration was evaluated by titrating increasing doses of drug or vehicle (a white square, double-deionized water; b white triangle, DMSO). After maximal respiration was reached, the contribution of non-mitochondrial respiration to total respiration was evaluated by addition of the complex III inhibitor antimycin A (1 μg/ml) followed by the complex IV inhibitor sodium azide (10 mM). The residual respiration shows the non-mitochondrial respiration at the highest dose of each drug. Data are expressed as mean ± SD. Non-linear curve fitting was applied for generation of the dose-response curves. n = 4. Two-way ANOVA with Bonferroni post hoc test was performed for analysis of differences. **p < 0.01, ***p < 0.001, compared to vehicle control

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