title: 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.
abstract: Qingre Liyan decoction (QYD), a Traditional Chinese medicine, and N-acetyl cysteine (NAC) have been used to prevent radiation induced mucositis. This work evaluates the protective mechanisms of QYD, NAC, and their combination (NAC-QYD) at the cellular and transcriptional level. A validated organotypic model of oral mucosal consisting of a three-dimensional (3D) cell tissue-culture of primary human keratinocytes exposed to X-ray irradiation was used. Six hours after the irradiation, the tissues were evaluated by hematoxylin and eosin (H and E) and a TUNEL assay to assess histopathology and apoptosis, respectively. Total RNA was extracted and used for microarray gene expression profiling. The tissue-cultures treated with NAC-QYD preserved their integrity and showed no apoptosis. Microarray results revealed that the NAC-QYD caused the upregulation of genes encoding metallothioneins, 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 NFκB 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, NFκB, and DNA repair factors.
authors.affiliation: College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Lambros
authors.affiliation: College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Kondapalli
authors.affiliation: College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA 91766, USA.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Parsa
authors.affiliation: College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
authors.forename: Hari Chandana
authors.initials: HC
authors.lastname: Mulamalla
authors.affiliation: College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA 91766, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Orlando
authors.affiliation: College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
authors.forename: Doreen
authors.initials: D
authors.lastname: Pon
authors.affiliation: College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA ; Center for Advancement of Drug Research and Evaluation, Western University of Health Sciences, Pomona, CA 91766, USA.
authors.forename: Moses S S
authors.initials: MS
authors.lastname: Chow