Department of Oral Medicine & Pathology, Institute of Odontology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
School of Clinical Dentistry, University of Sheffield, Sheffield, UK.
J Oral Pathol Med. 2018 May;47(5):477-483. doi: 10.1111/jop.12696. Epub 2018 Mar 15.
The cytotoxic effect of chemotherapeutic agents to the oral mucosa, as a side effect of cancer treatment, is a major problem. Cooling the oral mucosa using ice chips in conjunction with chemotherapy is known to reduce the severity of oral mucositis. However, although the use of ice chips is of clinical value, this method of cooling has inherent problems including discomfort for the patient, non-uniformity and fluctuations in cooling temperature throughout the oral cavity. Furthermore, despite being used clinically, it is not known what reduction in temperature is required to prevent oral mucositis. The aim of this study was therefore to determine in vitro if the cytotoxic effect of 5-fluorouracil (5-FU) on the oral mucosa could be reduced by lowering the temperature during chemotherapeutic treatment.
Tissue-engineered oral mucosal (TEOM) models were incubated at 20, 25, 30 or 35°C for 30 minutes followed by exposure to a clinically relevant concentration of 5-FU (162 μg/mL) for 2 hours and compared with untreated models (35°C). Cell viability and inflammatory cytokine production (IL-6 and TNF-α) were measured using PrestoBlue and ELISA, respectively.
TEOM models incubated at 20°C showed an increased cell viability and had a reduced IL-6 and TNF-α production compared to models treated with 5-FU incubated at 35°C.
This study demonstrates a reduced cytotoxic effect to the TEOM by reducing the temperature of the tissue during chemotherapy treatment and suggests that decreasing the temperature to 20°C could have clinical advantages.
化疗药物对口腔黏膜的细胞毒性作用是癌症治疗的一种副作用，这是一个主要问题。在化疗的同时使用冰屑冷却口腔黏膜被认为可以降低口腔黏膜炎的严重程度。然而，尽管冰屑的使用具有临床价值，但这种冷却方法存在一些固有问题，包括患者不适、口腔内冷却温度的不均匀性和波动。此外，尽管在临床上使用，但尚不清楚需要降低多少温度才能预防口腔黏膜炎。因此，本研究旨在体外确定在化疗治疗过程中降低温度是否可以降低 5-氟尿嘧啶（5-FU）对口腔黏膜的细胞毒性作用。
组织工程口腔黏膜（TEOM）模型在 20、25、30 或 35°C 下孵育 30 分钟，然后暴露于临床相关浓度的 5-FU（162μg/mL）2 小时，并与未经处理的模型（35°C）进行比较。使用 PrestoBlue 和 ELISA 分别测量细胞活力和炎症细胞因子（IL-6 和 TNF-α）的产生。
与在 35°C 下孵育的 5-FU 处理的模型相比，在 20°C 下孵育的 TEOM 模型显示出增加的细胞活力和减少的 IL-6 和 TNF-α 产生。
本研究通过在化疗治疗过程中降低组织温度来降低 TEOM 的细胞毒性作用，并表明将温度降低到 20°C 可能具有临床优势。
