Hexarelin alleviates apoptosis on ischemic acute kidney injury via MDM2/p53 pathway.

Guan C, Li C, Shen X, Yang C, Liu Z, Zhang N, Xu L, Zhao L, Zhou B, Man X, Luo C, Luan H, Che L, Wang Y, Xu Y

European journal of medical research14 Sept 2023Cited by 11 (Europe PMC)

PMID37710348PMCIDPMC10500723DOI10.1186/s40001-023-01318-wPepBankPUB-37710348

Summary

IntroductionHexarelin exhibits significant protection against organ injury in models of ischemia/reperfusion (I/R)-induced injury (IRI). Nevertheless, the impact of Hexarelin on acute kidney injury (AKI) and its underlying mechanism remains unclear. In this study, we investigated the therapeutic potential of Hexarelin in I/R-induced AKI and elucidated its molecular mechanisms.MethodsWe assessed the protective effects of Hexarelin through both in vivo and in vitro experiments. In the I/R-induced AKI model, rats were pretreated with Hexarelin at 100 μg/kg/d for 7 days before being sacrificed 24 h post-IRI. Subsequently, kidney function, histology, and apoptosis were assessed. In vitro, hypoxia/reoxygenation (H/R)-induced HK-2 cell model was used to investigate the impact of Hexarelin on apoptosis in HK-2 cells. Then, we employed molecular docking using a pharmmapper server and autodock software to identify potential target proteins of Hexarelin.ResultsIn this study, rats subjected to I/R developed severe kidney injury characterized by tubular necrosis, tubular dilatation, increased serum creatinine levels, and cell apoptosis. However, pretreatment with Hexarelin exhibited a protective effect by mitigating post-ischemic kidney pathological changes, improving renal function, and inhibiting apoptosis. This was achieved through the downregulation of conventional apoptosis-related genes, such as Caspase-3, Bax and Bad, and the upregulation of the anti-apoptotic protein Bcl-2. Consistent with the in vivo results, Hexarelin also reduced cell apoptosis in post-H/R HK-2 cells. Furthermore, our analysis using GSEA confirmed the essential role of the apoptosis pathway in I/R-induced AKI. Molecular docking revealed a strong binding affinity between Hexarelin and MDM2, suggesting the potential mechanism of Hexarelin's anti-apoptosis effect at least partially through its interaction with MDM2, a well-known negative regulator of apoptosis-related protein that of p53. To validate these findings, we evaluated the relative expression of MDM2 and p53 in I/R-induced AKI with or without Hexarelin pre-administration and observed a significant suppression of MDM2 and p53 by Hexarelin in both in vivo and in vitro experiments.ConclusionCollectively, Hexarelin was identified as a promising medication in protecting apoptosis against I/R-induced AKI.

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

Results from this study9

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

01AnimalAnimal study (in vivo)Efficacy outcome
In rats with ischemia/reperfusion-induced acute kidney injury, hexarelin pretreatment mitigated post-ischemic kidney pathological changes.
In plain wordsIn rats with kidney injury from interrupted blood flow, hexarelin given beforehand reduced the damage seen in kidney tissue.
Peptide
Hexarelin
Outcome
DecreasePost-ischemic kidney pathological changes
Study
ratn: not reported in source
Ischemia/reperfusion-induced acute kidney injury
Outcome group
Organ injury · Kidney and urinary
Studied dose
100 μg/kg/d · 7 days before ischemia/reperfusionAs given in this study (rat).
Source sentences
Summary
pretreatment with Hexarelin exhibited a protective effect by mitigating post-ischemic kidney pathological changes
1 context sentence(design, population, supporting numbers)
Summary · context
In the I/R-induced AKI model, rats were pretreated with Hexarelin at 100 μg/kg/d for 7 days before being sacrificed 24 h post-IRI.
Show in the study text Report a problemFND-3771034801
02AnimalAnimal study (in vivo)Efficacy outcome
In rats with ischemia/reperfusion-induced acute kidney injury, hexarelin pretreatment improved renal function.
In plain wordsIn rats with kidney injury from interrupted blood flow, hexarelin given beforehand improved kidney function.
Peptide
Hexarelin
Outcome
IncreaseRenal function
Study
ratn: not reported in source
Ischemia/reperfusion-induced acute kidney injury
Outcome group
Kidney function · Kidney and urinary
Studied dose
100 μg/kg/d · 7 days before ischemia/reperfusionAs given in this study (rat).
Source sentences
Summary
improving renal function
1 context sentence(design, population, supporting numbers)
Summary · context
In the I/R-induced AKI model, rats were pretreated with Hexarelin at 100 μg/kg/d for 7 days before being sacrificed 24 h post-IRI.
Show in the study text Report a problemFND-3771034802
03AnimalAnimal study (in vivo)Efficacy outcome
In rats with ischemia/reperfusion-induced acute kidney injury, hexarelin pretreatment inhibited apoptosis.
In plain wordsIn rats with kidney injury from interrupted blood flow, hexarelin given beforehand reduced cell death in the kidney.
Peptide
Hexarelin
Outcome
DecreaseKidney apoptosis
Study
ratn: not reported in source
Ischemia/reperfusion-induced acute kidney injury
Outcome group
Organ injury · Kidney and urinary
Studied dose
100 μg/kg/d · 7 days before ischemia/reperfusionAs given in this study (rat).
Source sentences
Summary
inhibiting apoptosis.
1 context sentence(design, population, supporting numbers)
Summary · context
In the I/R-induced AKI model, rats were pretreated with Hexarelin at 100 μg/kg/d for 7 days before being sacrificed 24 h post-IRI.
Show in the study text Report a problemFND-3771034803
04AnimalAnimal study (in vivo)Mechanism
In rats with ischemia/reperfusion-induced acute kidney injury, hexarelin downregulated the apoptosis-related genes Caspase-3, Bax and Bad.
In plain wordsIn rats with kidney injury from interrupted blood flow, hexarelin lowered activity of genes that drive cell death.
Peptide
Hexarelin
Outcome
DecreaseCaspase-3, Bax and Bad expression
Study
ratn: not reported in source
Ischemia/reperfusion-induced acute kidney injury
Outcome group
Organ injury · Kidney and urinary
Studied dose
100 μg/kg/d · 7 days before ischemia/reperfusionAs given in this study (rat).
Source sentences
Summary
the downregulation of conventional apoptosis-related genes, such as Caspase-3, Bax and Bad
1 context sentence(design, population, supporting numbers)
Summary · context
In the I/R-induced AKI model, rats were pretreated with Hexarelin at 100 μg/kg/d for 7 days before being sacrificed 24 h post-IRI.
Show in the study text Report a problemFND-3771034804
05AnimalAnimal study (in vivo)Mechanism
In rats with ischemia/reperfusion-induced acute kidney injury, hexarelin upregulated the anti-apoptotic protein Bcl-2.
In plain wordsIn rats with kidney injury from interrupted blood flow, hexarelin raised levels of a protein that protects cells from death.
Peptide
Hexarelin
Outcome
IncreaseBcl-2 expression
Study
ratn: not reported in source
Ischemia/reperfusion-induced acute kidney injury
Outcome group
Organ injury · Kidney and urinary
Studied dose
100 μg/kg/d · 7 days before ischemia/reperfusionAs given in this study (rat).
Source sentences
Summary
the upregulation of the anti-apoptotic protein Bcl-2.
1 context sentence(design, population, supporting numbers)
Summary · context
In the I/R-induced AKI model, rats were pretreated with Hexarelin at 100 μg/kg/d for 7 days before being sacrificed 24 h post-IRI.
Show in the study text Report a problemFND-3771034805
06AnimalAnimal study (in vivo)Mechanism
In rats with ischemia/reperfusion-induced acute kidney injury, hexarelin pre-administration significantly suppressed MDM2 and p53.
In plain wordsIn rats with kidney injury from interrupted blood flow, hexarelin given beforehand lowered levels of the MDM2 and p53 proteins.
Peptide
Hexarelin
Outcome
DecreaseMDM2 and p53 expression in kidney
Study
ratn: not reported in source
Ischemia/reperfusion-induced acute kidney injury
Outcome group
Organ injury · Kidney and urinary
Studied dose
100 μg/kg/d · 7 days before ischemia/reperfusionAs given in this study (rat).
Source sentences
Summary
observed a significant suppression of MDM2 and p53 by Hexarelin in both in vivo and in vitro experiments.
1 context sentence(design, population, supporting numbers)
Summary · context
In the I/R-induced AKI model, rats were pretreated with Hexarelin at 100 μg/kg/d for 7 days before being sacrificed 24 h post-IRI.
Show in the study text Report a problemFND-3771034806
07LabIn vitro (cells)Efficacy outcome
In HK-2 human kidney cells after hypoxia/reoxygenation, hexarelin reduced cell apoptosis.
In plain wordsIn cells, hexarelin reduced cell death in human kidney cells exposed to low oxygen followed by reoxygenation.
Peptide
Hexarelin
Outcome
DecreaseApoptosis in post-H/R HK-2 cells
Study
humann: not reported in source
Hypoxia/reoxygenation-induced HK-2 cells
Outcome group
Organ injury · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
Consistent with the in vivo results, Hexarelin also reduced cell apoptosis in post-H/R HK-2 cells.
1 context sentence(design, population, supporting numbers)
Summary · context
In vitro, hypoxia/reoxygenation (H/R)-induced HK-2 cell model was used to investigate the impact of Hexarelin on apoptosis in HK-2 cells.
Show in the study text Report a problemFND-3771034807
08LabIn vitro (cells)Mechanism
In HK-2 human kidney cells after hypoxia/reoxygenation, hexarelin significantly suppressed MDM2 and p53.
In plain wordsIn cells, hexarelin lowered levels of the MDM2 and p53 proteins in human kidney cells exposed to low oxygen followed by reoxygenation.
Peptide
Hexarelin
Outcome
DecreaseMDM2 and p53 expression in HK-2 cells
Study
humann: not reported in source
Hypoxia/reoxygenation-induced HK-2 cells
Outcome group
Organ injury · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
observed a significant suppression of MDM2 and p53 by Hexarelin in both in vivo and in vitro experiments.
1 context sentence(design, population, supporting numbers)
Summary · context
In vitro, hypoxia/reoxygenation (H/R)-induced HK-2 cell model was used to investigate the impact of Hexarelin on apoptosis in HK-2 cells.
Show in the study text Report a problemFND-3771034808
09Computer modelIn silicoActivity measurement
Molecular docking predicted a strong binding affinity between hexarelin and MDM2.
In plain wordsIn computer docking, hexarelin was predicted to bind strongly to the MDM2 protein.
Peptide
Hexarelin
Outcome
Not applicableBinding affinity of hexarelin for MDM2
Study
n: not reported in source
Molecular docking (pharmmapper server and autodock)
Outcome group
Receptor activity and mechanism · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
Molecular docking revealed a strong binding affinity between Hexarelin and MDM2
1 context sentence(design, population, supporting numbers)
Summary · context
Then, we employed molecular docking using a pharmmapper server and autodock software to identify potential target proteins of Hexarelin.
Show in the study text Report a problemFND-3771034809

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
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

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