Differential metabolic responses to hydrogen peroxide-induced oxidative stress in parotid and submandibular gland acinar cell lines

This study explored how oxidative stress induced by hydrogen peroxide alters metabolite levels in submandibular and parotid salivary gland acinar cells. We investigated the impact of oxidative stress on the metabolite profiles of two salivary gland cell lines and examined differences in response. Rat-derived immortalized acinar epithelial cell lines from the parotid and submandibular salivary glands were exposed to 50 μM and 150 μM hydrogen peroxide for 24 h. Metabolite levels were then analyzed using liquid chromatography mass spectrometry, and succinate levels were independently assessed using a succinic acid quantification kit. We observed a metabolic divergence between the two cell types. Succinate, fumarate, malate, and aspartate levels were increased in parotid gland cells but decreased in submandibular gland cells. Conversely, NADPH levels increased in submandibular gland cells but remained below the limit of detection in parotid gland cells. Both cell types exhibited glutathione depletion and oxidized glutathione accumulation. Notably, submandibular gland cells exhibited a distinct metabolic shift in response to 150 μM hydrogen peroxide exposure. Submandibular gland cells demonstrated superior redox adaptability compared to the metabolic vulnerability observed in parotid gland cells. These findings provide a metabolic basis for the differential radiosensitivity of salivary glands and may inform biomarker discovery for monitoring and preserving gland function in oxidative stress-related diseases.