Molecular Signatures in the Prevention of Radiation Damage by the Synergistic Effect of N-Acetyl Cysteine and Qingre Liyan Decoction, a Traditional Chinese Medicine, Using a 3-Dimensional Cell Culture Model of Oral Mucositis

Qingre Liyan decoction (QYD), a Traditional Chinesemedicine, andN-acetyl cysteine (NAC) have been used to prevent radiatio ninduce dmucositis.Tiswork evaluates the protectivemechanisms ofQYD,NAC, and their combination(NAC-QYD) at the cellular and transcriptional level. A validated organotypic model of ora lmucosal consisting of a three-dimensional (3D) cell tissue-culture of primary human keratinocytes exposed to X-ray irradiation was used. Six hours aſter the irradiation, the tissues were evaluated by hematoxylin and eosin (Hand E) and aTUNELassay to assess histopathology and apoptosis, respectively. TotalRNA was extractedand used for microarray gene expression profiling.Tetissue-cultures treatedwithNAC-QYDpreserved their integrity and showed no apoptosis.Microarray results revealed that theNAC-QYDcaused the upregulation of genes encodingmetallothioneins,HMOX1, and other components of the Nrf2 pathway, which protects against oxidative stress. DNA repair genes (XCP, GADD45G, RAD9, and XRCC1), protective genes (EGFR and PPARD), and genes of the NF휅B pathway were upregulated. Finally, tissue-cultures treated prophylactically with NAC-QYD showed significant downregulation of apoptosis, cytokines and chemokines genes, and constrained damage-associated molecular patterns (DAMPs). NAC-QYD treatment involves the protective effect of Nrf2, NF휅B, and DNA repair factors.

ORL-200, Oral Mucositis TUNEL assay,  histopathology, apoptosis, microarray gene expression, gene expression profiling, DNA repair genes, XCP, GADD45G, RAD9, XRCC1, DNA protective genes, EGFR, PPARD, NF-kappa-B pathway, constrained damage-associated molecular patterns (DAMPs), Nrf2

Qingre Liyan decoction (QYD), N-acetyl cysteine, gamma irradiation