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Related Concept Videos

Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

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Related Experiment Video

Updated: Jun 21, 2026

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
15:43

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Published on: January 7, 2013

Tacrolimus and sirolimus decrease oxidative phosphorylation of isolated rat kidney mitochondria.

Nicolas Simon1, Christophe Morin, Saïk Urien

  • 1Laboratoire de Pharmacologie, Faculté de Médecine de Marseille, 27 Bd Jean Moulin, F-13385 Marseille cedex, France. Nicolas.simon@medecine.univ-mrs.fr

British Journal of Pharmacology
|January 24, 2003
PubMed
Summary

Tacrolimus and sirolimus, potent immunosuppressors, impair mitochondrial respiration in rat kidneys at therapeutic concentrations. This uncoupling effect may contribute to long-term kidney toxicity observed in transplant patients.

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Last Updated: Jun 21, 2026

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15:43

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Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
08:38

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS

Published on: November 8, 2015

Area of Science:

  • Pharmacology
  • Nephrology
  • Mitochondrial Biology

Background:

  • Tacrolimus and sirolimus are crucial immunosuppressants in organ transplantation.
  • Tacrolimus is suspected to affect mitochondrial respiration, but sirolimus's effects remain unevaluated.
  • Understanding these drugs' mitochondrial impact is vital for managing transplant patient outcomes.

Purpose of the Study:

  • To investigate the in vitro effects of tacrolimus and sirolimus on oxidative phosphorylation in isolated rat kidney mitochondria.
  • To determine if these immunosuppressants alter mitochondrial respiration at therapeutic concentrations.
  • To explore potential cellular consequences and clinical implications, including nephrotoxicity.

Main Methods:

  • Isolated rat kidney mitochondria were utilized for in vitro experiments.
  • Oxygen consumption was measured using a Clark-type electrode to assess mitochondrial respiration.
  • The effects on state 3 and state 4 respiration, respiratory control ratio, and EC50 values were quantified.

Main Results:

  • Both tacrolimus and sirolimus increased resting mitochondrial respiration (state 4) but did not significantly affect ADP-stimulated respiration (state 3).
  • A concentration-dependent decrease in respiratory control ratio was observed, with maximal inhibition of 20% for tacrolimus and 14% for sirolimus.
  • An uncoupling effect on oxidative phosphorylation was noted, linked to reduced inner mitochondrial membrane fluidity.

Conclusions:

  • Tacrolimus and sirolimus exhibit an uncoupling effect on mitochondrial oxidative phosphorylation at therapeutic concentrations.
  • These findings suggest a potential mechanism for long-term nephrotoxicity associated with tacrolimus and raise concerns about sirolimus potentiating cyclosporine A-induced nephrotoxicity.