Interplay Between Sepsis and Ferroptosis: Unraveling Molecular Insights on Cellular Integrity

Sathish Jawahar; Karthika S; Shalinipriya Mc; Venkatesh Gunasekaran

doi:10.52794/hujpharm.1809259

Interplay Between Sepsis and Ferroptosis: Unraveling Molecular Insights on Cellular Integrity

Abstract

Sepsis is a complex, life-threatening disease characterized by multiple organ failure due to an abnormal systemic response to infection. Its multifaceted pathophysiology involves a dynamic balance linked pro-inflammatory and anti-inflammatory mediators, coagulation activation, and altered cellular functions. Although different kinds of regulated cell death (RCD) are implicated in sepsis pathogenesis, ferroptosis has emerged as an iron-mediated cell death. Molecular drivers of ferroptosis include iron accumulation, lipid peroxidation, production of reactive oxygen species (ROS), and inhibition of Glutathione peroxidase 4 (GPX4), eventually causing cell death. Current pre-clinical studies are aimed at modulating the ferroptosis pathway, and clinical studies are exploring the therapeutic strategies across diseases. The connection between sepsis and ferroptosis is bound by cellular abnormalities participating in several RCD mechanisms, including apoptosis, pyroptosis, necroptosis, ferroptosis, and autophagy. These cellular abnormalities encompass mitochondrial shrinkage, collapse of cristae, increased membrane density, activation of unfolded protein response, hydrolytic enzyme leakage, and enhanced lysosomal degradation. Additionally, genes associated with ferroptosis, such as Mitogen-Activated Protein Kinase 14 (MAPK14), Acyl-CoA Synthetase Long-Chain Family Member (ACSL4), Ribonucleotide Reductase Regulatory Subunit M2 (RRM2), and GPX4, have altered expression during sepsis, which impacts both the susceptibility and the progression of ferroptotic cell death.

Keywords

Supporting Institution

The authors acknowledge PSG College of Pharmacy for providing the necessary facilities and academic resources for this work.

Project Number

1

Ethical Statement

This article does not contain any studies involving human participants or animals performed by any of the authors.

Thanks

The authors express their sincere thanks to all Co-authers , for their support and critical insights.

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Details

Primary Language

English

Subjects

Basic Pharmacology

Journal Section

Review

Authors

Sathish Jawahar
0009-0005-3831-814X
India

Karthika S
0009-0006-8667-6360
India

Shalinipriya Mc
0009-0001-6516-0190
India

Venkatesh Gunasekaran ^*
0000-0002-4057-520X
India

Publication Date

September 1, 2026

Submission Date

October 23, 2025

Acceptance Date

August 19, 2026

Published in Issue

Year 2026 Volume: 46 Number: 3

DOI

https://doi.org/10.52794/hujpharm.1809259

IZ

https://izlik.org/JA33PA84EX

Cite

RIS / Bibtex

APA

Jawahar, S., S, K., Mc, S., & Gunasekaran, V. (2026). Interplay Between Sepsis and Ferroptosis: Unraveling Molecular Insights on Cellular Integrity. Hacettepe University Journal of the Faculty of Pharmacy, 46(3), 261-272. https://doi.org/10.52794/hujpharm.1809259

AMA

1.Jawahar S, S K, Mc S, Gunasekaran V. Interplay Between Sepsis and Ferroptosis: Unraveling Molecular Insights on Cellular Integrity. HUJPHARM. 2026;46(3):261-272. doi:10.52794/hujpharm.1809259

Chicago

Jawahar, Sathish, Karthika S, Shalinipriya Mc, and Venkatesh Gunasekaran. 2026. “Interplay Between Sepsis and Ferroptosis: Unraveling Molecular Insights on Cellular Integrity”. Hacettepe University Journal of the Faculty of Pharmacy 46 (3): 261-72. https://doi.org/10.52794/hujpharm.1809259.

EndNote

Jawahar S, S K, Mc S, Gunasekaran V (September 1, 2026) Interplay Between Sepsis and Ferroptosis: Unraveling Molecular Insights on Cellular Integrity. Hacettepe University Journal of the Faculty of Pharmacy 46 3 261–272.

IEEE

[1]S. Jawahar, K. S, S. Mc, and V. Gunasekaran, “Interplay Between Sepsis and Ferroptosis: Unraveling Molecular Insights on Cellular Integrity”, HUJPHARM, vol. 46, no. 3, pp. 261–272, Sept. 2026, doi: 10.52794/hujpharm.1809259.

ISNAD

Jawahar, Sathish - S, Karthika - Mc, Shalinipriya - Gunasekaran, Venkatesh. “Interplay Between Sepsis and Ferroptosis: Unraveling Molecular Insights on Cellular Integrity”. Hacettepe University Journal of the Faculty of Pharmacy 46/3 (September 1, 2026): 261-272. https://doi.org/10.52794/hujpharm.1809259.

JAMA

1.Jawahar S, S K, Mc S, Gunasekaran V. Interplay Between Sepsis and Ferroptosis: Unraveling Molecular Insights on Cellular Integrity. HUJPHARM. 2026;46:261–272.

MLA

Jawahar, Sathish, et al. “Interplay Between Sepsis and Ferroptosis: Unraveling Molecular Insights on Cellular Integrity”. Hacettepe University Journal of the Faculty of Pharmacy, vol. 46, no. 3, Sept. 2026, pp. 261-72, doi:10.52794/hujpharm.1809259.

Vancouver

1.Sathish Jawahar, Karthika S, Shalinipriya Mc, Venkatesh Gunasekaran. Interplay Between Sepsis and Ferroptosis: Unraveling Molecular Insights on Cellular Integrity. HUJPHARM. 2026 Sep. 1;46(3):261-72. doi:10.52794/hujpharm.1809259