N-Acetylcysteine Amide Is a Potential Novel Radioprotector of Salivary Gland Function

<b>Background:</b> Radiation-induced salivary gland (SG) hypofunction is mediated via microvascular dysfunction and radical oxygen species. N-acetylcysteine amide (NACA) has shown antioxidant properties with low toxicity. We explored NACA's potential as a radioprotector of SG function. <b>Methods:</b> Bovine aortic endothelial cells (BAECs) were treated with NACA before irradiation with a single 10 Gy dose. Apoptosis was assessed by bis-benzimide staining and quantified via fluorescence microscopy. In vivo, NACA was administered to mice prior to a single 15 Gy head and neck irradiation. Eight weeks post-irradiation, saliva production was measured using pilocarpine stimulation; lysozyme levels were analyzed by ELISA. SGs were collected for immunohistochemistry. <b>Results:</b> BAEC apoptosis was substantially lower in NACA-treated cells vs. radiation-only (10% vs. 23%). In vivo, mice lost significant weight and developed severe hair loss eight weeks post-irradiation-attenuated by NACA pretreatment. Saliva production was reduced by 72% post-radiation, with a corresponding drop in lysozyme. NACA increased salivary flow by 42% and prevented lysozyme reduction. Post-radiation decline in microvessel density was also prevented by NACA. <b>Conclusions:</b> These outcomes suggest NACA may serve as a radioprotector of SG function in patients undergoing radiotherapy for head and neck cancer.