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Therapeutic potential of c-Raf in LPS-stimulated acute lung injury: Anti-inflammatory and protective effects in mice model

Renas Younus Haddad
Department of Clinical Analysis, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
Mohammed Merza
Department of Clinical Analysis, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
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Copyright (c) 2025 Renas Younus Haddad, Mohammed Merza (Author)

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Abstract

Background and objective: Acute lung injury (ALI) it considered as a very serious illness characterized by inflammatory lung swelling, leading to acute hypoxic respiratory failure. c-Raf G-protein has been shown to regulate inflammation we predicted that c-Raf could regulate neutrophil infiltration in LPS induced sepsis in mice model.

Methods: 18 albino mice (6 weeks age, weighing 26±2 grams) were randomly assigned to three groups: the control group (they were injected by normal saline intraperitoneally, n=6), the LPS (lipopolysaccharide) group (50 mg/kg LPS Were injected intraperitoneally, n=6), the GW5074 + LPS group (2 mg/kg of the selective c-Raf inhibitor GW5074 were given intraperitoneally 15 minutes before LPS injection, n=6). After 24 hours, the mice were sacrificed, then inflammatory cell counts, proinflammatory cytokines (TNF-α, IL-1β, MPO activity, CXCL-2, IL-6) were measured. The lungs were then isolated for molecular target analysis, histopathological, and immunohistochemical evaluations.

Results: Resemble to the LPS group, pretreatment of mice with c-Raf inhibitor significantly decreased MPO, CXCL-2, TNF-α, IL-1β and IL-6, activity. GW5074 weakened migration and infiltration of inflammatory cells, showing a marked reduce in MPO (6.0 ±0.2 vs. 2.2±2.0 P <0.05) as well as CXCL-2(132.8± 2.0 vs. 80.4±6.0 P <0.05) in the sham, LPS, and GW5074 + LPS. Additionally, IL-6 levels in treatment group significantly decrease compared with LPS group (123 ± 4.0 vs. 71.2 ± 6.0 P <0.05).

Conclusion: The conclusions of this research propose that c-Raf may have anti-inflammatory and protective effects against LPS-stimulated ALI in mice.

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How to Cite
Haddad, R. Y., & Merza, M. . (2025). Therapeutic potential of c-Raf in LPS-stimulated acute lung injury: Anti-inflammatory and protective effects in mice model. Zanco Journal of Medical Sciences (Zanco J Med Sci), 29(3), 652–657. https://doi.org/10.15218/zjms.2025.070

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