Evaluation of oxidative stress and the microenvironment in oral submucous fibrosis

Oral Submucous fibrosis (OSF) is a chronic inflammatory mucosal disease of unknown etiology. Statistics show cases of OSF which has a high rate of overall prevalence and increase the chance of malignant transformation. As we know malignant cells is situated in a very complex microenvironment with altered metabolic pathway including intermediates which participate in oxidative stress process which enhances metabolic rewiring and promotes tumor progression. This study aims to evaluate the tumor microenvironment and their role in metabolic reprogramming.

This study was conducted on the serum sample of OSF (n = 20) compared to the healthy group (n = 20) using ELISA. The serum levels of intermediate by-products of metabolic pathway and oxidative stress induced biomolecular damage products were determined. The sensitivity of results was analyzed by correlating it with markers of metabolic status (Glucose, Total cholesterol, Total protein).

Metabolic pathway intermediates molecules like Fatty Acids (FAA), Ascorbic acid, Citrate, Oxaloacetate (OAA), levels were significantly high in the serum of OSF cases. This indicated that intermediates act as a metabolic switch that drives cells to adapt malignant transformation pathway. Markers related to oxidative DNA damage (8-hydroxy-2' -deoxyguanosine), Oxidative lipid peroxidation (8-epi-Prostaglandin F2α), and Protein carbonyl were significantly up-regulated. This significant increase in oxidative stress marker revealed the reprogramming of the metabolic pathway for fulfilling the nutritional requirement of cancer cells. A further significant correlation was observed with metabolic products confirmed altered metabolic status.

Our findings could identify the differentiating intermediate pathway metabolites and oxidative damage to biomolecules that are leading to rewiring of metabolism in the OSF group. Findings described in the study can be helpful to explain further the molecular aspects that lead to the progression of OSF towards carcinogenesis.