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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.

Lambros MP, Kondapalli L, Parsa C, Mulamalla HC, Orlando R, Pon D, Huang Y, Chow MS - Evid Based Complement Alternat Med (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.

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.

No MeSH data available.


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A schematic representation of the proposed molecular signatures which were elicited by the synergistic effect of NAC-QYD and prevented the radiation damage.
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fig3: A schematic representation of the proposed molecular signatures which were elicited by the synergistic effect of NAC-QYD and prevented the radiation damage.

Mentions: EGFR was upregulated significantly in the NAC-QYD-treated tissues and downregulated in the nontreated irradiated tissues. Signaling through EGFR has been shown to induce NFκB activation and enhance cell survival, whereas blocking EGFR signaling results in the inhibition of NFκB [37, 38]. A schematic representation of the protective molecular signatures discussed above is shown in Figure 3.


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.

Lambros MP, Kondapalli L, Parsa C, Mulamalla HC, Orlando R, Pon D, Huang Y, Chow MS - Evid Based Complement Alternat Med (2015)

A schematic representation of the proposed molecular signatures which were elicited by the synergistic effect of NAC-QYD and prevented the radiation damage.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4326035&req=5

fig3: A schematic representation of the proposed molecular signatures which were elicited by the synergistic effect of NAC-QYD and prevented the radiation damage.
Mentions: EGFR was upregulated significantly in the NAC-QYD-treated tissues and downregulated in the nontreated irradiated tissues. Signaling through EGFR has been shown to induce NFκB activation and enhance cell survival, whereas blocking EGFR signaling results in the inhibition of NFκB [37, 38]. A schematic representation of the protective molecular signatures discussed above is shown in Figure 3.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.

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.

No MeSH data available.


Related in: MedlinePlus