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Cardiac Immune Cell–Mediated Inflammatory Responses Exacerbate Myocardial Cell Injury in Mice

Daniel R. Whitfield, PhD1, Anil Kumar Sharma, PhD, Priya Menon, PhD ORCID *

1 Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), New Delhi, India

DOI: 10.18081/2378-5225/14.120  
Cited by 0

 Article history: Received 22 August 2025 · Revised 13 September 2025 · Accepted 01 October 2025 · Published 22 October 2025

© 2025 Donnelly, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0). 

CC BY 4.0                                                                                                   

Abstract

Background: Edox homeostasis is critical for maintaining cellular integrity, and its disruption has been increasingly implicated in cancer progression. Tumor cells are frequently exposed to sustained oxidative stress, resulting in cellular injury that paradoxically promotes survival and adaptation. However, the integrated role of redox dysregulation–induced cellular injury in driving tumor adaptation in vivo remains insufficiently understood. This study investigated the contribution of redox dysregulation and oxidative stress–mediated cellular injury to tumor adaptation using a rat experimental tumor model.

Methods: Tumors were induced in Wistar rats using a chemically mediated carcinogenesis protocol. Oxidative stress markers, antioxidant enzyme activities, and redox balance were assessed in tumor tissues at different stages of progression. Cellular injury was evaluated through biochemical indices of membrane damage, protein oxidation, DNA oxidative injury, and mitochondrial dysfunction. Histopathological analysis and immunohistochemistry were performed to assess tissue injury and activation of redox-responsive adaptive signaling pathways. Gene expression analysis was used to examine molecular responses associated with tumor adaptation.

Results: Tumor tissues exhibited pronounced redox dysregulation, characterized by elevated lipid peroxidation and depletion of intracellular glutathione. Antioxidant defenses showed selective modulation, with reduced superoxide dismutase and catalase activities and compensatory upregulation of glutathione peroxidase. Markers of cellular injury, including lactate dehydrogenase release, protein carbonyl accumulation, and oxidative DNA damage, were significantly increased in tumors. Mitochondrial membrane potential and ATP levels were markedly reduced, indicating mitochondrial injury and altered bioenergetics. Histological analysis revealed progressive tissue injury with reduced necrosis in advanced tumors, suggesting adaptive survival. Redox-responsive and stress-related signaling pathways were significantly upregulated and correlated with reduced injury severity and enhanced tumor adaptation.

Conclusions: The findings demonstrate that sustained redox dysregulation induces widespread cellular injury while simultaneously driving adaptive responses that promote tumor survival and progression. These results highlight redox imbalance as a central pathophysiological mechanism in tumor adaptation and underscore its potential as a therapeutic target, particularly in cancers associated with chronic oxidative stress.

Keywords: Redox dysregulation; oxidative stress; cellular injury; tumor adaptation; rat model; cancer pathophysiology.

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BM-Publisher · Pathophysiology of Cell Injury Journal (PCIJ) · E-ISSN 2378-5225 · DOI Prefix 10.18081/pcij/2378-5225

Pathophysiology of Cell Injury Journal (PCIJ)
E-ISSN 2378-5225 · Biannual
BM-Publisher (London, UK)
Open Access

Vol 14, Issue 2 (October 2025), pp. 120–139

How to cite (AMA)

Sharma A, Menon P. Redox Dysregulation and Cellular Injury Drive Tumor Adaptation in a Rat Model. Pathophysiology of Cell Injury Journal (PCIJ). 2025;14(2):120–139. doi: 10.18081/2378-5225/14.120.

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