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MansouraUniversity: Pharma102 Rupatadine modulates TLR4/MYD88/NF-κB and AKT/PI3K signaling pathways, attenuating sepsis-induced liver injury in mice

Rupatadine modulates TLR4/MYD88/NF-κB and AKT/PI3K signaling pathways, attenuating sepsis-induced liver injury in mice

MansouraUniversity
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About Rupatadine Alleviates Sepsis-Induced Liver Injury by Modulating TLR4/NF-κB and PI3K/AKT Signaling Pathways in Mice Search

Sepsis — a life-threatening medical condition that triggers widespread inflammation, multi-organ failure, and high mortality rates in intensive care units — remains one of the most urgent challenges in global healthcare. Among the most vulnerable organs during sepsis is the liver, which suffers severe inflammatory and oxidative stress, often leading to irreversible damage. Against this critical backdrop, a research team from the Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University — Dr. Abeer G. Sakr, Dr. Hoda E. Kafl, and Dr. Dalia H. El-Kashef — introduces a novel therapeutic hypothesis: repurposing the well-known antihistamine Rupatadine to protect against sepsis-induced liver injury.

Study Overview

Rupatadine, a second-generation antihistamine widely prescribed for allergic conditions, has shown promising anti-inflammatory and immunomodulatory properties. This study aimed to explore its potential beyond allergy treatment, targeting critical immune signaling pathways — TLR4/MYD88/NF-κB and PI3K/AKT — that are deeply involved in sepsis pathogenesis.

Using a carefully designed mouse model, researchers divided the subjects into three groups: a healthy control group, a sepsis group, and two rupatadine-treated groups (3 and 6 mg/kg). The team conducted a comprehensive analysis, including liver enzyme assays (ALT, AST), oxidative stress biomarkers (MDA, GSH), histopathological liver tissue examination, and protein expression profiling for inflammatory mediators and signaling pathway components.

Key Findings

    • Liver Function: Rupatadine significantly reduced ALT and AST levels, indicating functional recovery.
    • Oxidative Stress: MDA levels were decreased, while GSH levels were enhanced, reflecting boosted antioxidant defenses.
    • Histology: Microscopic analysis revealed restored liver architecture and reduced tissue damage.
    • Molecular Pathways: Downregulation of TLR4, MYD88, NF-κB was observed, alongside rebalancing of the PI3K/AKT signaling cascade, reducing inflammatory overactivation.

Why This Study Matters

With no definitive cure for sepsis-induced liver injury, this research introduces a cost-effective and clinically feasible approach by repurposing an existing drug with a well-established safety profile. It highlights how targeting immune signaling can open new therapeutic avenues for managing severe systemic inflammation.

Who Should Watch This Lecture?

This in-depth lecture is essential for:

    • Researchers in pharmacology, toxicology, and immunology who are seeking novel intervention strategies.
    • Clinicians manage critical care and inflammatory disorders, looking for translational applications.
    • Postgraduate students in medical and pharmaceutical sciences aim to understand preclinical study design.
    • Drug development professionals are interested in repurposing strategies.
    • Faculty and academics engaged in animal model-based experimental research.

Authors and Contributors

Dr. Dalia El Kashef

- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University.

About Knowture Platform

Knowture is an academic digital platform under the Postgraduate Studies Sector at Mansoura University, Egypt. It specializes in delivering high-quality, research-based content for postgraduate students, with the goal of bridging applied science and academic knowledge across diverse disciplines.

Publication Reference

This research has been peer-reviewed and published in a reputable scientific journal. You can access the full paper via PubMed: https://pubmed.ncbi.nlm.nih.gov/40562198/

Course Summary

  1. Course Number

    Pharma102

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