Mitochondria as the Bridge between Injury and Protection: The Role of Melatonin in Non-Steroidal Anti-Inflammatory Drug-Induced Gastric Ulcers

Debasish Bandyopadhyay^1,*, Romit Majumder^1,2,#, Madhuri Datta^1,2,#, Adrita Banerjee^1,2, Aindrila Chattopadhyay²
1 Oxidative Stress and Free Radical Biology Laboratory, Department of Physiology, University of Calcutta, 92, APC Road, Kolkata, India
2 Department of Physiology, Vidyasagar College, 39, Sankar Ghosh Lane, Kolkata, India
* Corresponding Author: Debasish Bandyopadhyay. Email: email , email
# These authors contributed equally to this work

BIOCELL https://doi.org/10.32604/biocell.2026.075963

Received 11 November 2025; Accepted 22 January 2026; Published online 11 February 2026

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Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed, but their long-term use frequently results in gastric mucosal injury. Emerging evidence indicates that, beyond cyclooxygenase inhibition, mitochondrial dysfunction represents a central mechanism driving NSAID-induced gastric epithelial damage. This review aims to critically synthesize current evidence on mitochondria-centered pathways involved in NSAID-induced gastric ulceration and to evaluate the therapeutic relevance of melatonin in this context. We highlight how NSAIDs impair mitochondrial bioenergetics, promote excessive reactive oxygen species generation, disrupt membrane potential, and activate apoptotic signaling, thereby compromising mucosal integrity. Importantly, melatonin exerts multifaceted gastroprotective actions by preserving mitochondrial function, restoring redox homeostasis, modulating apoptosis, and facilitating mucosal repair. Collectively, the available data identify mitochondria as both the primary site of injury and a viable therapeutic target in NSAID-induced gastric ulcers. This mechanistic framework positions melatonin as a promising adjunct strategy for mitigating NSAID-associated gastric damage and improving mucosal defense.