Restoring the Hypoxic Microenvironment in Oral Submucous Fibrosis Through Intralesional Nitroglycerin: A Therapeutic Hypothesis

ABSTRACT Background Oral submucous fibrosis (OSMF) is a progressive oral potentially malignant disorder where persistent fibrosis, microvascular compromise and tissue hypoxia leads to functional impairment. Current therapies mainly target inflammation, collagen deposition or restricted motion, but the hypoxic vascular microenvironment is not sufficiently addressed. Hypothesis We hypothesize that local nitric oxide donation by intralesional nitroglycerin may restore microvascular perfusion in fibrotic tissues and change the hypoxic environment of OSMF. Possible Mechanism Nitric oxide may induce vasodilation, increase local blood flow and tissue oxygenation, and stimulate angiogenesis by activating soluble guanylate cyclase. These effects may indirectly alleviate hypoxia‐related fibrotic signalling, increase tissue compliance and improve mouth opening rather than direct collagenolytic effect. Conclusion Intralesional nitroglycerin represents a mechanistically plausible, vascular‐targeted therapeutic hypothesis for OSMF. However, its safety, optimal dose, administration protocol and clinical efficacy remain unestablished. Sequential preclinical studies followed by carefully designed clinical trials are essential before clinical translation.