**5. Conclusions**

Taken together, we show new findings about organ-specific and concentration-dependent e ffects of two clinically important and widely used drugs, pravastatin and gemfibrozil, on hepatic and colonic mitochondrial respiration. Results from this study reveal a rather negative e ffect of both drugs on hepatic mitochondrial respiration. This could possibly be one of the mechanisms contributing to elevated liver enzymes during the therapy with these drugs. This hypothesis must be considered very carefully because we examined the mitochondrial oxygen consumption, which depicts only one aspect of the complex mitochondrial function within a cell. Furthermore, our experiments are conducted in vitro with animal tissues and these adverse e ffects are not fully understood and are complex processes including many factors like preexisting organ damage and co-medication.

The positive e ffects of pravastatin and gemfibrozil on colonic mitochondria could contribute to adaptive cell mechanisms under pathological conditions like sepsis or hemorrhagic shock, where tissue hypoxia may occur, allowing better oxygen utilization. Also in this case, the results must be interpreted very cautiously and further research in this field is needed. Our data extend our knowledge about a possible mode of action of both drugs and o ffer a new insight into conceivable mechanisms of their side e ffects.

**Author Contributions:** Conceptualization: A.H., I.B. and O.P.; Methodology: A.H. and E.L.; Software: A.H. and E.L.; Validation: A.H., E.L., J.S. and R.T.; Formal Analysis: A.H, I.B. and O.P.; Investigation: A.H. and E.L.; Resources: I.B. and O.P.; Data Curation: A.H. and E.L.; Writing—Original Draft Preparation: A.H.; Writing—Review and Editing: A.H., J.S., R.T., C.V., I.B. and O.P.; Visualization: A.H.; Supervision: C.V., I.B. and O.P.; Project Administration: A.H., I.B., O.P.

**Funding:** This research received no external funding.

**Acknowledgments:** The authors would like to thank Adelheid Weidinger for scientifical and Birgitt Berke and Claudia Dohle for technical support.

**Conflicts of Interest:** The authors declare no conflict of interest.
