Related Experiment Video
Updated: Oct 26, 2025
Standardized Colon Ascendens Stent Peritonitis in Rats - a Simple, Feasible Animal Model to Induce Septic Acute Kidney Injury
Published on: February 15, 2022
Selective mitochondrial antioxidant MitoTEMPO reduces renal dysfunction and systemic inflammation in experimental
Nishkantha Arulkumaran1, Sean J Pollen1, Robert Tidswell1
1Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, London, UK.
Background:
Excess mitochondrial reactive oxygen species (mROS) in sepsis is associated with organ failure, in part by generating inflammation through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome. We determined the impact of a mitochondrial-targeted antioxidant (MitoTEMPO) on mitochondrial dysfunction in renal proximal tubular epithelial cells, peritoneal immune cell function ex vivo, and organ dysfunction in a rat model of sepsis.
Methods:
The effects of MitoTEMPO were assessed ex vivo using adenosine triphosphate and lipopolysaccharide-stimulated rat peritoneal immune cells and fresh rat kidney slices exposed to serum from septic rats. We assessed mROS production and phagocytotic capacity (flow cytometry), mitochondrial functionality (multiphoton imaging, respirometry), and NLRP3 inflammasome activation in cell culture. The effect of MitoTEMPO on organ dysfunction was evaluated in a rat model of faecal peritonitis.
Results:
MitoTEMPO decreased septic serum-induced mROS (P<0.001) and maintained normal reduced nicotinamide adenine dinucleotide redox state (P=0.02) and mitochondrial membrane potential (P<0.001) in renal proximal tubular epithelial cells ex vivo. In lipopolysaccharide-stimulated peritoneal immune cells, MitoTEMPO abrogated the increase in mROS (P=0.006) and interleukin-1β (IL-1β) (P=0.03) without affecting non-mitochondrial oxygen consumption or the phagocytotic-induced respiratory burst (P>0.05). In vivo, compared with untreated septic animals, MitoTEMPO reduced systemic IL-1β (P=0.01), reduced renal oxidative stress as determined by urine isoprostane levels (P=0.04), and ameliorated renal dysfunction (reduced serum urea (P<0.001) and creatinine (P=0.05).
Conclusions:
Reduction of mROS by a mitochondria-targeted antioxidant reduced IL-1β, and protected mitochondrial, cellular, and organ functionality after septic insults.
Insights
Mitochondrial-targeted antioxidants like MitoTEMPO can reduce inflammation and protect organs during sepsis. This study shows MitoTEMPO mitigates mitochondrial dysfunction and improves outcomes in a rat sepsis model.
Area of Science:
- Biomedical Science
- Cellular Biology
- Pathophysiology
Background:
- Sepsis-induced excess mitochondrial reactive oxygen species (mROS) contribute to organ failure by activating the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome.
- Mitochondrial dysfunction plays a critical role in the pathophysiology of sepsis-associated organ damage.
Purpose of the Study:
- To investigate the therapeutic potential of MitoTEMPO, a mitochondrial-targeted antioxidant, in mitigating sepsis-induced mitochondrial dysfunction and organ injury.
- To evaluate the impact of MitoTEMPO on mROS production, inflammasome activation, and cellular and organ function in sepsis.
Main Methods:
- Ex vivo assessment of MitoTEMPO effects on immune cells and kidney cells exposed to septic serum.
- Measurement of mROS, mitochondrial function, and inflammasome activation in vitro.
- In vivo evaluation of MitoTEMPO's impact on organ dysfunction in a rat model of sepsis.
Main Results:
- MitoTEMPO significantly reduced mROS and preserved mitochondrial function in renal cells exposed to septic serum.
- In immune cells, MitoTEMPO decreased mROS and interleukin-1β (IL-1β) production without affecting phagocytosis.
- In vivo, MitoTEMPO treatment reduced systemic IL-1β, renal oxidative stress, and ameliorated renal dysfunction in septic rats.
Conclusions:
- Targeting mitochondrial ROS with antioxidants like MitoTEMPO can effectively reduce inflammation (IL-1β) and protect mitochondrial, cellular, and organ function following septic insults.
- MitoTEMPO demonstrates promise as a therapeutic agent for sepsis by addressing key mechanisms of organ damage.
More Related Videos
Related Concept Videos
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
01:45Mitochondrial Membranes