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Study · In vitro (cells) · rat · 2016

10 results

AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function.

Kang SW, Haydar G, Taniane C, Farrell G, Arias IM, Lippincott-Schwartz J, Fu D

PloS one28 Oct 2016Cited by 83 (Europe PMC)

PMID27792760 (opens in a new tab)PMCIDPMC5085033 (opens in a new tab)DOI10.1371/journal.pone.0165638 (opens in a new tab)PepBankPUB-27792760
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Summary

Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK). When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury.
CC0Text 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.

  1. 01LabIn vitro (cells)Mechanism

    In rat and human hepatocyte cultures, AICAR prevented and reversed drug-induced loss of viability.

    In plain wordsIn lab tests, AICAR protected hepatocyte survival compared with hepatotoxic drug exposure alone.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseHepatocyte viability
    Study

    rat and humann: not reported in source

    Collagen sandwich hepatocyte cultures exposed to acetaminophen or diclofenac
    Comparator
    Hepatotoxic drug exposure without AMPK activation
    Outcome group
    Cell viability and death · Liver
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects.
    2 context sentences
    Summary · context
    In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability.
    Summary · context
    To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac.
  2. 02LabIn vitro (cells)Mechanism

    In rat and human hepatocyte cultures, AICAR prevented and reversed drug-induced loss of mitochondrial membrane potential.

    In plain wordsIn lab tests, AICAR protected mitochondrial membrane potential compared with hepatotoxic drug exposure alone.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseMitochondrial membrane potential
    Study

    rat and humann: not reported in source

    Collagen sandwich hepatocyte cultures exposed to acetaminophen or diclofenac
    Comparator
    Hepatotoxic drug exposure without AMPK activation
    Outcome group
    Mitochondrial function · Liver
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects.
    2 context sentences
    Summary · context
    At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1.
    Summary · context
    To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac.
  3. 03LabIn vitro (cells)Mechanism

    In drug-exposed rat and human hepatocyte cultures, AICAR promoted highly fused mitochondria.

    In plain wordsIn lab tests, AICAR increased mitochondrial fusion compared with hepatotoxic drug exposure alone.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseMitochondrial fusion
    Study

    rat and humann: not reported in source

    Collagen sandwich hepatocyte cultures exposed to acetaminophen or diclofenac
    Comparator
    Hepatotoxic drug exposure without AMPK activation
    Outcome group
    Mitochondrial function · Liver
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology.
    2 context sentences
    Summary · context
    To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac.
    Summary · context
    Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects.
  4. 04LabIn vitro (cells)Mechanism

    In drug-exposed rat and human hepatocyte cultures, AICAR increased ATP production.

    In plain wordsIn lab tests, AICAR increased ATP production compared with hepatotoxic drug exposure alone.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseATP production
    Study

    rat and humann: not reported in source

    Collagen sandwich hepatocyte cultures exposed to acetaminophen or diclofenac
    Comparator
    Hepatotoxic drug exposure without AMPK activation
    Outcome group
    Mitochondrial function · Liver
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology.
    2 context sentences
    Summary · context
    To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac.
    Summary · context
    Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects.
  5. 05LabIn vitro (cells)Mechanism

    In drug-exposed rat and human hepatocyte cultures, AICAR maintained polarized hepatocyte morphology.

    In plain wordsIn lab tests, AICAR preserved hepatocyte shape compared with hepatotoxic drug exposure alone.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreasePolarized hepatocyte morphology
    Study

    rat and humann: not reported in source

    Collagen sandwich hepatocyte cultures exposed to acetaminophen or diclofenac
    Comparator
    Hepatotoxic drug exposure without AMPK activation
    Outcome group
    Cytoskeleton and cell structure · Liver
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology.
    2 context sentences
    Summary · context
    To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac.
    Summary · context
    Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects.
  6. 06LabIn vitro (cells)Mechanism

    In hepatocyte cultures, AICAR-associated AMPK activation prevented drug-mediated decreases in Mfn1 expression.

    In plain wordsIn lab tests, AICAR prevented the loss of Mfn1 compared with hepatotoxic drug exposure alone.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseMfn1 expression
    Study

    rat and humann: not reported in source

    Collagen sandwich hepatocyte cultures exposed to acetaminophen or diclofenac
    Comparator
    Hepatotoxic drug exposure without AMPK activation
    Outcome group
    Mitochondrial function · Liver
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1.
    2 context sentences
    Summary · context
    To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac.
    Summary · context
    Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects.
  7. 07LabIn vitro (cells)Mechanism

    In hepatocyte cultures, AICAR-associated AMPK activation prevented drug-mediated decreases in Mfn2 expression.

    In plain wordsIn lab tests, AICAR prevented the loss of Mfn2 compared with hepatotoxic drug exposure alone.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseMfn2 expression
    Study

    rat and humann: not reported in source

    Collagen sandwich hepatocyte cultures exposed to acetaminophen or diclofenac
    Comparator
    Hepatotoxic drug exposure without AMPK activation
    Outcome group
    Mitochondrial function · Liver
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1.
    2 context sentences
    Summary · context
    To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac.
    Summary · context
    Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects.
  8. 08LabIn vitro (cells)Mechanism

    In hepatocyte cultures, AICAR-associated AMPK activation prevented drug-mediated decreases in Opa1 expression.

    In plain wordsIn lab tests, AICAR prevented the loss of Opa1 compared with hepatotoxic drug exposure alone.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseOpa1 expression
    Study

    rat and humann: not reported in source

    Collagen sandwich hepatocyte cultures exposed to acetaminophen or diclofenac
    Comparator
    Hepatotoxic drug exposure without AMPK activation
    Outcome group
    Mitochondrial function · Liver
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1.
    2 context sentences
    Summary · context
    To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac.
    Summary · context
    Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects.
  9. 09LabIn vitro (cells)Mechanism

    In hepatocyte cultures, AICAR-associated AMPK activation stimulated autophagy, most significantly in acetaminophen-treated cells.

    In plain wordsIn cells, AICAR increased autophagy compared with drug exposure alone, most significantly with acetaminophen.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseAutophagy
    Study

    rat and humann: not reported in source

    Collagen sandwich hepatocyte cultures exposed to acetaminophen or diclofenac
    Comparator
    Hepatotoxic drug exposure without AMPK activation
    Outcome group
    Receptor activity and mechanism · Liver
    Studied dose
    Dose not stated

    Source sentences

    Summary
    AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells.
    2 context sentences
    Summary · context
    To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac.
    Summary · context
    Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects.
  10. 10LabIn vitro (cells)Mechanism

    In hepatocyte cultures, AICAR-associated AMPK activation stimulated mitophagy, most significantly in acetaminophen-treated cells.

    In plain wordsIn cells, AICAR increased mitophagy compared with drug exposure alone, most significantly with acetaminophen.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseMitophagy
    Study

    rat and humann: not reported in source

    Collagen sandwich hepatocyte cultures exposed to acetaminophen or diclofenac
    Comparator
    Hepatotoxic drug exposure without AMPK activation
    Outcome group
    Mitochondrial function · Liver
    Studied dose
    Dose not stated

    Source sentences

    Summary
    AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells.
    2 context sentences
    Summary · context
    To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac.
    Summary · context
    Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects.

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.

  1. Version 2Current

    21 Oct 2026, 15:58 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 12:50 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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