AICAR, an AMP-Activated Protein Kinase Activator, Ameliorates Acute Pancreatitis-Associated Liver Injury Partially Through Nrf2-Mediated Antioxidant Effects and Inhibition of NLRP3 Inflammasome Activation.

Kong L, Zhang H, Lu C, Shi K, Huang H, Zheng Y, Wang Y, Wang D, Wang H, Huang W

Frontiers in pharmacology31 Aug 2021Cited by 30 (Europe PMC)

PMID34531748PMCIDPMC8438129DOI10.3389/fphar.2021.724514PepBankPUB-34531748

Summary

Acute pancreatitis (AP) is a highly fatal acute inflammation and is often accompanied by multiple organ dysfunction syndrome (MODS). The liver, one of the most vulnerable extrapancreatic organs in AP, is the major organ involved in the evolution of the disease and correlates strongly with the occurrence of MODS. However, the etiology of pancreatitis-associated liver injury (PALI) has not been clarified and currently lacks an effective treatment. 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) is a cell permeable nucleoside with pleiotropic effects on anti-inflammatory and antioxidant stress that binds with adenosine monophosphate protein kinase (AMPK) and induces AMPK activation. However, the role of AICAR in PALI remains elusive. Here, we show that activation of AMPK by AICAR, a direct AMPK agonist, significantly ameliorates sodium taurocholate-induced PALI in rats, whereas treatment of PALI rats with the AMPK antagonist Compound C profoundly exacerbates the degree of liver injury, suggesting that hepatic AMPK activation exerts an essential protective role in PALI. Mechanistically, AICAR induces AMPK activation, which in turn activates nuclear factor erythroid 2-related factor 2(Nrf2) -regulated hepatic antioxidant capacity and inhibits NLRP3 inflammasome-mediated pyrolysis, protecting rats from sodium taurocholate-induced PALI. In addition, Nrf2 deficiency strikingly weakens the beneficial effects of AICAR on alleviation of liver injury, oxidative stress and NLRP3 inflammasome activation in L-arginine-induced PALI mice. Thus, AICAR protects against PALI in rodents by triggering AMPK, which is mediated at least in part by Nrf2-modulated antioxidant effects and NLRP3 inflammasome activation.

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

Results from this study7

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

01AnimalAnimal study (in vivo)Efficacy outcome
In rats, AICAR ameliorated pancreatitis-associated liver injury.
In plain wordsIn rats, AICAR reduced pancreatitis-associated liver injury.
Peptide
AICAR (acadesine)
Outcome
DecreaseLiver injury
Study
ratn: not reported in source
sodium taurocholate-induced pancreatitis-associated liver injury
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated
Source sentences
Summary
Here, we show that activation of AMPK by AICAR, a direct AMPK agonist, significantly ameliorates sodium taurocholate-induced PALI in rats,
Show in the study text Report a problemFND-3453174801
02AnimalAnimal study (in vivo)Mechanism
In rats, AICAR activated AMPK.
In plain wordsIn rats, AICAR activated AMPK.
Peptide
AICAR (acadesine)
Outcome
IncreaseAMPK activation
Study
ratn: not reported in source
sodium taurocholate-induced pancreatitis-associated liver injury
Outcome group
Receptor activity and mechanism · Liver
Studied dose
Dose not stated
Source sentences
Summary
Mechanistically, AICAR induces AMPK activation, which in turn activates nuclear factor erythroid 2-related factor 2(Nrf2) -regulated hepatic antioxidant capacity and inhibits NLRP3 inflammasome-mediated pyrolysis, protecting rats from sodium taurocholate-induced PALI.
Show in the study text Report a problemFND-3453174802
03AnimalAnimal study (in vivo)Mechanism
In rats, AICAR activated Nrf2-regulated hepatic antioxidant capacity.
In plain wordsIn rats, AICAR increased liver antioxidant capacity through Nrf2.
Peptide
AICAR (acadesine)
Outcome
IncreaseHepatic antioxidant capacity
Study
ratn: not reported in source
sodium taurocholate-induced pancreatitis-associated liver injury
Outcome group
Receptor activity and mechanism · Liver
Studied dose
Dose not stated
Source sentences
Summary
Mechanistically, AICAR induces AMPK activation, which in turn activates nuclear factor erythroid 2-related factor 2(Nrf2) -regulated hepatic antioxidant capacity and inhibits NLRP3 inflammasome-mediated pyrolysis, protecting rats from sodium taurocholate-induced PALI.
Show in the study text Report a problemFND-3453174803
04AnimalAnimal study (in vivo)Mechanism
In rats, AICAR inhibited NLRP3 inflammasome-mediated pyrolysis.
In plain wordsIn rats, AICAR inhibited NLRP3 inflammasome-mediated cell damage.
Peptide
AICAR (acadesine)
Outcome
DecreaseNLRP3 inflammasome-mediated pyrolysis
Study
ratn: not reported in source
sodium taurocholate-induced pancreatitis-associated liver injury
Outcome group
Inflammation markers · Liver
Studied dose
Dose not stated
Source sentences
Summary
Mechanistically, AICAR induces AMPK activation, which in turn activates nuclear factor erythroid 2-related factor 2(Nrf2) -regulated hepatic antioxidant capacity and inhibits NLRP3 inflammasome-mediated pyrolysis, protecting rats from sodium taurocholate-induced PALI.
Show in the study text Report a problemFND-3453174804

Studies that did not test the peptide alone3

In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking AICAR (acadesine).

05AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In mice, Nrf2 deficiency weakened AICAR-associated alleviation of liver injury.
In plain wordsIn mice, Nrf2 deficiency weakened liver protection associated with AICAR.
Peptide
AICAR (acadesine)
Outcome
DecreaseLiver injury protection after Nrf2 deficiency
Study
mousen: not reported in source
Nrf2-deficient L-arginine-induced PALI
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
In addition, Nrf2 deficiency strikingly weakens the beneficial effects of AICAR on alleviation of liver injury, oxidative stress and NLRP3 inflammasome activation in L-arginine-induced PALI mice.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3453174805
06AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In mice, Nrf2 deficiency weakened AICAR-associated alleviation of oxidative stress.
In plain wordsIn mice, Nrf2 deficiency weakened oxidative stress protection associated with AICAR.
Peptide
AICAR (acadesine)
Outcome
DecreaseOxidative stress protection after Nrf2 deficiency
Study
mousen: not reported in source
Nrf2-deficient L-arginine-induced PALI
Outcome group
Inflammation markers · Liver
Source sentences
Summary
In addition, Nrf2 deficiency strikingly weakens the beneficial effects of AICAR on alleviation of liver injury, oxidative stress and NLRP3 inflammasome activation in L-arginine-induced PALI mice.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3453174806
07AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In mice, Nrf2 deficiency weakened AICAR-associated alleviation of NLRP3 inflammasome activation.
In plain wordsIn mice, Nrf2 deficiency weakened NLRP3 inhibition associated with AICAR.
Peptide
AICAR (acadesine)
Outcome
DecreaseNLRP3 inhibition after Nrf2 deficiency
Study
mousen: not reported in source
Nrf2-deficient L-arginine-induced PALI
Outcome group
Inflammation markers · Liver
Source sentences
Summary
In addition, Nrf2 deficiency strikingly weakens the beneficial effects of AICAR on alleviation of liver injury, oxidative stress and NLRP3 inflammasome activation in L-arginine-induced PALI mice.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3453174807

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
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

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Terms as the source lists them.

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Keywords

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