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Study · Animal study (in vivo) · rat · 2026

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Differential Protective Actions of Dulaglutide and Dexamethasone in Methotrexate Induced Pulmonary Fibrosis: Relationship with AMPK and Beclin-1 Levels.

Maher OW, El-Sayed NM, El-Awady EE, El-Orabi NF, Radwan A

Biomedicines30 Jul 2026

PMID42652097 (opens in a new tab)PMCIDPMC13509837 (opens in a new tab)DOI10.3390/biomedicines14081714 (opens in a new tab)PepBankPUB-42652097
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Summary

Background and Objectives: Pulmonary fibrosis (PF) is a life-threatening respiratory disorder involving complex pathophysiological mechanisms such as inflammation, collagen deposition, and epithelial cell injury. Methotrexate (MTX), a chemotherapeutic and immunosuppressive agent, is frequently associated with pulmonary toxicity, representing a significant adverse effect with unpredictable outcomes. Thus, the current study investigates the possible protective effect of dulaglutide (DUL) against MTX-induced lung injury. Methods: Sixty male Wistar rats were allocated into six groups: group 1 served as a control group, group 2 received MTX (14 mg/kg/week, p.o) for 2 weeks, group 3 was treated with MTX treatment (14 mg/kg/week, p.o) prior to dexamethasone (DEXA) (0.5 mg/kg/week i.p), Groups 4-5 were treated concurrently with MTX (14 mg/kg/week, p.o) and DUL at doses of 0.05 and 0.1 mg/kg/week, s.c. and Group 6 received DUL (0.1 mg/kg/week, s.c.) only. Animals were sacrificed on day 15 for histopathological and biochemical assessments. Results: Our data demonstrated that MTX markedly increased some oxidative stress markers, inflammatory biomarkers and fibrotic and apoptotic indicators, alongside a significant decrease in Beclin-1 and Adenosine Monophosphate Activated Protein Kinase (AMPK) levels. DUL administration significantly ameliorated these alternations in a dose-dependent manner, with histopathological findings corroborating biochemical data through Hematoxylin & Eosin (H&E) and Mason's Trichrome (MTC) staining. Conclusions: DUL confers significant protection against MTX-induced pulmonary fibrosis, likely through its antioxidant, anti-inflammatory, and anti-apoptotic properties, which are associated with the restoration of total AMPK and Beclin-1 levels. This highlights its therapeutic potential in preventing drug-induced lung toxicity.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study1

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In rats with methotrexate-induced lung injury, dulaglutide dose-dependently ameliorated biochemical alterations, with supportive histopathology.

    In plain wordsIn rats with methotrexate-induced lung injury, dulaglutide improved biochemical alterations in a dose-dependent manner, with supportive tissue findings.

    Peptide
    Dulaglutide (Trulicity)
    Outcome
    MixedLung injury biochemical and histological alterations
    Study

    ratn: not reported in source

    Male Wistar rats with methotrexate-induced lung injury
    Outcome group
    Lung injury and fibrosis · Respiratory
    Studied dose
    0.05 and 0.1 mg/kg/week · subcutaneousAs given in this study (rat).

    Source sentences

    Summary
    DUL administration significantly ameliorated these alternations in a dose-dependent manner, with histopathological findings corroborating biochemical data through Hematoxylin & Eosin (H&E) and Mason's Trichrome (MTC) staining.
    3 context sentences
    Summary · context
    Our data demonstrated that MTX markedly increased some oxidative stress markers, inflammatory biomarkers and fibrotic and apoptotic indicators, alongside a significant decrease in Beclin-1 and Adenosine Monophosphate Activated Protein Kinase (AMPK) levels.
    Summary · context
    Groups 4-5 were treated concurrently with MTX (14 mg/kg/week, p.o) and DUL at doses of 0.05 and 0.1 mg/kg/week, s.c.
    Summary · context
    Animals were sacrificed on day 15 for histopathological and biochemical assessments.

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Version history

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  1. Version 2Current

    22 Oct 2026, 02:25 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 18:59 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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