Growth hormone releasing peptide-6 (GHRP-6) prevents doxorubicin-induced myocardial and extra-myocardial damages by activating prosurvival mechanisms.

Berlanga-Acosta J, Cibrian D, Valiente-Mustelier J, Suárez-Alba J, García-Ojalvo A, Falcón-Cama V, Jiang B, Wang L, Guillén-Nieto G

Frontiers in pharmacology30 May 2024Cited by 11 (Europe PMC)

PMID38873418PMCIDPMC11169835DOI10.3389/fphar.2024.1402138PepBankPUB-38873418

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Summary

Introduction: Dilated cardiomyopathy (DCM) is a fatal myocardial condition with ventricular structural changes and functional deficits, leading to systolic dysfunction and heart failure (HF). DCM is a frequent complication in oncologic patients receiving Doxorubicin (Dox). Dox is a highly cardiotoxic drug, whereas its damaging spectrum affects most of the organs by multiple pathogenic cascades. Experimentally reproduced DCM/HF through Dox administrations has shed light on the pathogenic drivers of cardiotoxicity. Growth hormone (GH) releasing peptide 6 (GHRP-6) is a GH secretagogue with expanding and promising cardioprotective pharmacological properties. Here we examined whether GHRP-6 administration concomitant to Dox prevented the onset of DCM/HF and multiple organs damages in otherwise healthy rats. Methods: Myocardial changes were sequentially evaluated by transthoracic echocardiography. Autopsy was conducted at the end of the administration period when ventricular dilation was established. Semiquantitative histopathologic study included heart and other internal organs samples. Myocardial tissue fragments were also addressed for electron microscopy study, and characterization of the transcriptional expression ratio between Bcl-2 and Bax. Serum samples were destined for REDOX system balance assessment. Results and discussion: GHRP-6 administration in parallel to Dox prevented myocardial fibers consumption and ventricular dilation, accounting for an effective preservation of the LV systolic function. GHRP-6 also attenuated extracardiac toxicity preserving epithelial organs integrity, inhibiting interstitial fibrosis, and ultimately reducing morbidity and mortality. Mechanistically, GHRP-6 proved to sustain cellular antioxidant defense, upregulate prosurvival gene Bcl-2, and preserve cardiomyocyte mitochondrial integrity. These evidences contribute to pave potential avenues for the clinical use of GHRP-6 in Dox-treated subjects.

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 doxorubicin-treated rats, GHRP‑6 prevented myocardial fiber consumption.
In plain wordsIn rats receiving doxorubicin, GHRP‑6 prevented heart muscle fiber loss compared with doxorubicin alone.
Peptide
GHRP-6
Outcome
DecreaseMyocardial fiber consumption
Study
ratn: not reported in source
Doxorubicin-induced myocardial and extra-myocardial injury
Comparator
Doxorubicin
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
GHRP-6 administration in parallel to Dox prevented myocardial fibers consumption and ventricular dilation, accounting for an effective preservation of the LV systolic function.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we examined whether GHRP-6 administration concomitant to Dox prevented the onset of DCM/HF and multiple organs damages in otherwise healthy rats.
Show in the study text Report a problemFND-3887341801
02AnimalAnimal study (in vivo)Efficacy outcome
In doxorubicin-treated rats, GHRP‑6 prevented ventricular dilation.
In plain wordsIn rats receiving doxorubicin, GHRP‑6 prevented ventricular widening compared with doxorubicin alone.
Peptide
GHRP-6
Outcome
DecreaseVentricular dilation
Study
ratn: not reported in source
Doxorubicin-induced myocardial and extra-myocardial injury
Comparator
Doxorubicin
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
GHRP-6 administration in parallel to Dox prevented myocardial fibers consumption and ventricular dilation, accounting for an effective preservation of the LV systolic function.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we examined whether GHRP-6 administration concomitant to Dox prevented the onset of DCM/HF and multiple organs damages in otherwise healthy rats.
Show in the study text Report a problemFND-3887341802
03AnimalAnimal study (in vivo)Efficacy outcome
In doxorubicin-treated rats, GHRP‑6 preserved LV systolic function.
In plain wordsIn rats receiving doxorubicin, GHRP‑6 preserved heart pumping function compared with doxorubicin alone.
Peptide
GHRP-6
Outcome
Direction not reportedLV systolic function
Study
ratn: not reported in source
Doxorubicin-induced myocardial and extra-myocardial injury
Comparator
Doxorubicin
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
GHRP-6 administration in parallel to Dox prevented myocardial fibers consumption and ventricular dilation, accounting for an effective preservation of the LV systolic function.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we examined whether GHRP-6 administration concomitant to Dox prevented the onset of DCM/HF and multiple organs damages in otherwise healthy rats.
Show in the study text Report a problemFND-3887341803
04AnimalAnimal study (in vivo)Efficacy outcome
In doxorubicin-treated rats, GHRP‑6 preserved epithelial organ integrity.
In plain wordsIn rats receiving doxorubicin, GHRP‑6 preserved epithelial organ integrity compared with doxorubicin alone.
Peptide
GHRP-6
Outcome
Direction not reportedEpithelial organ integrity
Study
ratn: not reported in source
Doxorubicin-induced myocardial and extra-myocardial injury
Comparator
Doxorubicin
Outcome group
Organ injury · Whole body
Studied dose
Dose not stated
Source sentences
Summary
GHRP-6 also attenuated extracardiac toxicity preserving epithelial organs integrity, inhibiting interstitial fibrosis, and ultimately reducing morbidity and mortality.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we examined whether GHRP-6 administration concomitant to Dox prevented the onset of DCM/HF and multiple organs damages in otherwise healthy rats.
Show in the study text Report a problemFND-3887341804
05AnimalAnimal study (in vivo)Efficacy outcome
In doxorubicin-treated rats, GHRP‑6 inhibited interstitial fibrosis.
In plain wordsIn rats receiving doxorubicin, GHRP‑6 reduced tissue scarring compared with doxorubicin alone.
Peptide
GHRP-6
Outcome
DecreaseInterstitial fibrosis
Study
ratn: not reported in source
Doxorubicin-induced myocardial and extra-myocardial injury
Comparator
Doxorubicin
Outcome group
Organ injury · Whole body
Studied dose
Dose not stated
Source sentences
Summary
GHRP-6 also attenuated extracardiac toxicity preserving epithelial organs integrity, inhibiting interstitial fibrosis, and ultimately reducing morbidity and mortality.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we examined whether GHRP-6 administration concomitant to Dox prevented the onset of DCM/HF and multiple organs damages in otherwise healthy rats.
Show in the study text Report a problemFND-3887341805
06AnimalAnimal study (in vivo)Efficacy outcome
In doxorubicin-treated rats, GHRP‑6 reduced morbidity.
In plain wordsIn rats receiving doxorubicin, GHRP‑6 reduced illness compared with doxorubicin alone.
Peptide
GHRP-6
Outcome
DecreaseMorbidity
Study
ratn: not reported in source
Doxorubicin-induced myocardial and extra-myocardial injury
Comparator
Doxorubicin
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated
Source sentences
Summary
GHRP-6 also attenuated extracardiac toxicity preserving epithelial organs integrity, inhibiting interstitial fibrosis, and ultimately reducing morbidity and mortality.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we examined whether GHRP-6 administration concomitant to Dox prevented the onset of DCM/HF and multiple organs damages in otherwise healthy rats.
Show in the study text Report a problemFND-3887341806
07AnimalAnimal study (in vivo)Safety outcome
In doxorubicin-treated rats, GHRP‑6 reduced mortality.
In plain wordsIn rats receiving doxorubicin, GHRP‑6 reduced deaths compared with doxorubicin alone.
Peptide
GHRP-6
Outcome
DecreaseMortality
Study
ratn: not reported in source
Doxorubicin-induced myocardial and extra-myocardial injury
Comparator
Doxorubicin
Outcome group
Mortality · Whole body
Studied dose
Dose not stated
Source sentences
Summary
GHRP-6 also attenuated extracardiac toxicity preserving epithelial organs integrity, inhibiting interstitial fibrosis, and ultimately reducing morbidity and mortality.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we examined whether GHRP-6 administration concomitant to Dox prevented the onset of DCM/HF and multiple organs damages in otherwise healthy rats.
Show in the study text Report a problemFND-3887341807
08AnimalAnimal study (in vivo)Mechanism
In doxorubicin-treated rats, GHRP‑6 sustained cellular antioxidant defense.
In plain wordsIn rats receiving doxorubicin, GHRP‑6 maintained cellular antioxidant defenses compared with doxorubicin alone.
Peptide
GHRP-6
Outcome
Direction not reportedCellular antioxidant defense
Study
ratn: not reported in source
Doxorubicin-induced myocardial and extra-myocardial injury
Comparator
Doxorubicin
Outcome group
Receptor activity and mechanism · Whole body
Studied dose
Dose not stated
Source sentences
Summary
Mechanistically, GHRP-6 proved to sustain cellular antioxidant defense, upregulate prosurvival gene Bcl-2, and preserve cardiomyocyte mitochondrial integrity.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we examined whether GHRP-6 administration concomitant to Dox prevented the onset of DCM/HF and multiple organs damages in otherwise healthy rats.
Show in the study text Report a problemFND-3887341808
09AnimalAnimal study (in vivo)Mechanism
In doxorubicin-treated rats, GHRP‑6 increased prosurvival Bcl-2 gene expression.
In plain wordsIn rats receiving doxorubicin, GHRP‑6 increased Bcl-2 gene expression compared with doxorubicin alone.
Peptide
GHRP-6
Outcome
IncreaseBcl-2 expression
Study
ratn: not reported in source
Doxorubicin-induced myocardial and extra-myocardial injury
Comparator
Doxorubicin
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Mechanistically, GHRP-6 proved to sustain cellular antioxidant defense, upregulate prosurvival gene Bcl-2, and preserve cardiomyocyte mitochondrial integrity.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we examined whether GHRP-6 administration concomitant to Dox prevented the onset of DCM/HF and multiple organs damages in otherwise healthy rats.
Show in the study text Report a problemFND-3887341809
10AnimalAnimal study (in vivo)Mechanism
In doxorubicin-treated rats, GHRP‑6 preserved cardiomyocyte mitochondrial integrity.
In plain wordsIn rats receiving doxorubicin, GHRP‑6 preserved heart muscle cell mitochondria compared with doxorubicin alone.
Peptide
GHRP-6
Outcome
Direction not reportedCardiomyocyte mitochondrial integrity
Study
ratn: not reported in source
Doxorubicin-induced myocardial and extra-myocardial injury
Comparator
Doxorubicin
Outcome group
Mitochondrial function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Mechanistically, GHRP-6 proved to sustain cellular antioxidant defense, upregulate prosurvival gene Bcl-2, and preserve cardiomyocyte mitochondrial integrity.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we examined whether GHRP-6 administration concomitant to Dox prevented the onset of DCM/HF and multiple organs damages in otherwise healthy rats.
Show in the study text Report a problemFND-3887341810

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
9 Oct 2026, 03:13 UTC
First added · source update from Europe PMC

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