A Mitochondrion-Targeted Antioxidant Ameliorates Isoflurane-Induced Cognitive Deficits in Aging Mice.

Wu J, Li H, Sun X, Zhang H, Hao S, Ji M, Yang J, Li K

PloS one17 Sept 2015Cited by 43 (Europe PMC)

PMID26379247PMCIDPMC4575031DOI10.1371/journal.pone.0138256PepBankPUB-26379247

Summary

Isoflurane possesses neurotoxicity and can induce cognitive deficits, particularly in aging mammals. Mitochondrial reactive oxygen species (mtROS) have been linked to the early pathogenesis of this disorder. However, the role of mtROS remains to be evaluated due to a lack of targeted method to treat mtROS. Here, we determined in aging mice the effects of the mitochondrion-targeted antioxidant SS-31, on cognitive deficits induced by isoflurane, a general inhalation anesthetic. We further investigated the possible mechanisms underlying the effects of SS-31 on hippocampal neuro-inflammation and apoptosis. The results showed that isoflurane induced hippocampus-dependent memory deficit, which was associated with mitochondrial dysfunction including reduced ATP contents, increased ROS levels, and mitochondrial swelling. Treatment with SS-31 significantly ameliorated isoflurane-induced cognitive deficits through the improvement of mitochondrial integrity and function. Mechanistically, SS-31 treatment suppressed pro-inflammatory responses by decreasing the levels of NF-κB, NLRP3, caspase 1, IL-1β, and TNF-α; and inhibited the apoptotic pathway by decreasing the Bax/Bcl-2 ratio, reducing the release of cytochrome C, and blocking the cleavage of caspase 3. Our results indicate that isoflurane-induced cognitive deficits may be attenuated by mitochondrion-targeted antioxidants, such as SS-31. Therefore, SS-31 may have therapeutic potentials in preventing injuries from oxidative stresses that contribute to anesthetic-induced neurotoxicity.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study10

10 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In aging mice, SS‑31 treatment ameliorated isoflurane-induced cognitive deficits.
In plain wordsIn aging mice, SS‑31 reduced the memory problems caused by the anaesthetic isoflurane.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseIsoflurane-induced cognitive deficits
Study
mousen: not reported in source
Aging mice with isoflurane-induced cognitive deficits
Comparator
Isoflurane without SS-31
Outcome group
Cognition and memory · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Treatment with SS-31 significantly ameliorated isoflurane-induced cognitive deficits
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we determined in aging mice the effects of the mitochondrion-targeted antioxidant SS-31, on cognitive deficits induced by isoflurane, a general inhalation anesthetic.
Show in the study text Report a problemFND-2637924701
02AnimalAnimal study (in vivo)Mechanism
In aging mice given isoflurane, SS‑31 improved mitochondrial integrity and function.
In plain wordsIn aging mice given isoflurane, SS‑31 improved the structure and function of mitochondria.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseMitochondrial integrity and function
Study
mousen: not reported in source
Aging mice with isoflurane-induced cognitive deficits
Comparator
Isoflurane without SS-31
Outcome group
Mitochondrial function · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Treatment with SS-31 significantly ameliorated isoflurane-induced cognitive deficits through the improvement of mitochondrial integrity and function.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we determined in aging mice the effects of the mitochondrion-targeted antioxidant SS-31, on cognitive deficits induced by isoflurane, a general inhalation anesthetic.
Show in the study text Report a problemFND-2637924702
03AnimalAnimal study (in vivo)Mechanism
In aging mice given isoflurane, SS‑31 decreased NF-κB levels.
In plain wordsIn aging mice given isoflurane, SS‑31 lowered the inflammation marker NF-κB.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseNF-κB level
Study
mousen: not reported in source
Aging mice with isoflurane-induced cognitive deficits
Comparator
Isoflurane without SS-31
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
Dose not stated
Source sentences
Summary
SS-31 treatment suppressed pro-inflammatory responses by decreasing the levels of NF-κB, NLRP3, caspase 1, IL-1β, and TNF-α
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we determined in aging mice the effects of the mitochondrion-targeted antioxidant SS-31, on cognitive deficits induced by isoflurane, a general inhalation anesthetic.
Show in the study text Report a problemFND-2637924703
04AnimalAnimal study (in vivo)Mechanism
In aging mice given isoflurane, SS‑31 decreased NLRP3 levels.
In plain wordsIn aging mice given isoflurane, SS‑31 lowered the inflammation marker NLRP3.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseNLRP3 level
Study
mousen: not reported in source
Aging mice with isoflurane-induced cognitive deficits
Comparator
Isoflurane without SS-31
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
Dose not stated
Source sentences
Summary
SS-31 treatment suppressed pro-inflammatory responses by decreasing the levels of NF-κB, NLRP3, caspase 1, IL-1β, and TNF-α
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we determined in aging mice the effects of the mitochondrion-targeted antioxidant SS-31, on cognitive deficits induced by isoflurane, a general inhalation anesthetic.
Show in the study text Report a problemFND-2637924704
05AnimalAnimal study (in vivo)Mechanism
In aging mice given isoflurane, SS‑31 decreased caspase 1 levels.
In plain wordsIn aging mice given isoflurane, SS‑31 lowered the inflammation marker caspase 1.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseCaspase 1 level
Study
mousen: not reported in source
Aging mice with isoflurane-induced cognitive deficits
Comparator
Isoflurane without SS-31
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
Dose not stated
Source sentences
Summary
SS-31 treatment suppressed pro-inflammatory responses by decreasing the levels of NF-κB, NLRP3, caspase 1, IL-1β, and TNF-α
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we determined in aging mice the effects of the mitochondrion-targeted antioxidant SS-31, on cognitive deficits induced by isoflurane, a general inhalation anesthetic.
Show in the study text Report a problemFND-2637924705
06AnimalAnimal study (in vivo)Mechanism
In aging mice given isoflurane, SS‑31 decreased IL-1β levels.
In plain wordsIn aging mice given isoflurane, SS‑31 lowered the inflammation marker IL-1β.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseIL-1β level
Study
mousen: not reported in source
Aging mice with isoflurane-induced cognitive deficits
Comparator
Isoflurane without SS-31
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
Dose not stated
Source sentences
Summary
SS-31 treatment suppressed pro-inflammatory responses by decreasing the levels of NF-κB, NLRP3, caspase 1, IL-1β, and TNF-α
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we determined in aging mice the effects of the mitochondrion-targeted antioxidant SS-31, on cognitive deficits induced by isoflurane, a general inhalation anesthetic.
Show in the study text Report a problemFND-2637924706
07AnimalAnimal study (in vivo)Mechanism
In aging mice given isoflurane, SS‑31 decreased TNF-α levels.
In plain wordsIn aging mice given isoflurane, SS‑31 lowered the inflammation marker TNF-α.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseTNF-α level
Study
mousen: not reported in source
Aging mice with isoflurane-induced cognitive deficits
Comparator
Isoflurane without SS-31
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
Dose not stated
Source sentences
Summary
SS-31 treatment suppressed pro-inflammatory responses by decreasing the levels of NF-κB, NLRP3, caspase 1, IL-1β, and TNF-α
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we determined in aging mice the effects of the mitochondrion-targeted antioxidant SS-31, on cognitive deficits induced by isoflurane, a general inhalation anesthetic.
Show in the study text Report a problemFND-2637924707
08AnimalAnimal study (in vivo)Mechanism
In aging mice given isoflurane, SS‑31 decreased the Bax/Bcl-2 ratio.
In plain wordsIn aging mice given isoflurane, SS‑31 lowered a marker of cell death signalling.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseBax/Bcl-2 ratio
Study
mousen: not reported in source
Aging mice with isoflurane-induced cognitive deficits
Comparator
Isoflurane without SS-31
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
inhibited the apoptotic pathway by decreasing the Bax/Bcl-2 ratio, reducing the release of cytochrome C, and blocking the cleavage of caspase 3.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we determined in aging mice the effects of the mitochondrion-targeted antioxidant SS-31, on cognitive deficits induced by isoflurane, a general inhalation anesthetic.
Show in the study text Report a problemFND-2637924708
09AnimalAnimal study (in vivo)Mechanism
In aging mice given isoflurane, SS‑31 reduced the release of cytochrome C.
In plain wordsIn aging mice given isoflurane, SS‑31 reduced the release of cytochrome C, a cell death signal.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseCytochrome C release
Study
mousen: not reported in source
Aging mice with isoflurane-induced cognitive deficits
Comparator
Isoflurane without SS-31
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
inhibited the apoptotic pathway by decreasing the Bax/Bcl-2 ratio, reducing the release of cytochrome C, and blocking the cleavage of caspase 3.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we determined in aging mice the effects of the mitochondrion-targeted antioxidant SS-31, on cognitive deficits induced by isoflurane, a general inhalation anesthetic.
Show in the study text Report a problemFND-2637924709
10AnimalAnimal study (in vivo)Mechanism
In aging mice given isoflurane, SS‑31 blocked the cleavage of caspase 3.
In plain wordsIn aging mice given isoflurane, SS‑31 blocked activation of caspase 3, a cell death enzyme.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseCaspase 3 cleavage
Study
mousen: not reported in source
Aging mice with isoflurane-induced cognitive deficits
Comparator
Isoflurane without SS-31
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
inhibited the apoptotic pathway by decreasing the Bax/Bcl-2 ratio, reducing the release of cytochrome C, and blocking the cleavage of caspase 3.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we determined in aging mice the effects of the mitochondrion-targeted antioxidant SS-31, on cognitive deficits induced by isoflurane, a general inhalation anesthetic.
Show in the study text Report a problemFND-2637924710

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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