Department of Dental Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Molecules. 2023 Mar 24;28(7):2935. doi: 10.3390/molecules28072935.
Oral mucositis is a typical adverse effect of chemotherapy, causing oral pain that significantly reduces the patient's quality of life. β-cryptoxanthin (β-cry) is a carotenoid abundant in citrus fruits with antioxidant and anti-inflammatory effects. However, the β-cry effect on oral mucositis remains unclear. We investigated the effects of 5-fluorouracil (5-FU) and β-cry on human normal oral mucosal keratinocytes (hOMK). hOMK was seeded on a culture plate and cultured with 5-FU and β-cry. The cell number, mRNA expression of inflammatory cytokines and matrix metalloproteinases (MMPs), and production of inflammatory cytokines in hOMK were evaluated. Additionally, the cell count and inflammatory cytokine production were analyzed when hOMK was co-stimulated with lipopolysaccharide ( LPS) in addition to 5-FU. The numbers of hOMK significantly reduced with 5-FU stimulation, whereas it increased with β-cry treatment. mRNA expression of interleukin (IL)-6, IL-8, metalloproteinase (MMP)-2, and MMP-9 and protein production of IL-6 and IL-8 in hOMK were augmented on 5-FU stimulation. Simultaneously, β-cry treatment significantly suppressed IL-8 and MMP-9 mRNA expression, and IL-8 production was induced on 5-FU stimulation. Co-stimulation with LPS and 5-FU enhanced IL-6 and IL-8 production in hOMK. β-cry could enhance cell proliferation and suppress 5-FU-induced expression of inflammatory cytokines and MMP in hOMK. Thus, β-cry can alleviate the symptoms of chemotherapy-induced oral mucositis, and its combination with oral care is effective in managing oral mucositis.
口腔黏膜炎是化疗的一种典型不良反应，导致口腔疼痛，显著降低患者的生活质量。β-隐黄质（β-cry）是柑橘类水果中丰富的类胡萝卜素，具有抗氧化和抗炎作用。然而，β-cry 对口腔黏膜炎的影响尚不清楚。我们研究了 5-氟尿嘧啶（5-FU）和 β-cry 对人正常口腔黏膜角质形成细胞（hOMK）的影响。hOMK 接种于培养板中，并与 5-FU 和 β-cry 一起培养。评估 hOMK 的细胞数量、炎症细胞因子和基质金属蛋白酶（MMPs）的 mRNA 表达以及炎症细胞因子的产生。此外，当 hOMK 与脂多糖（LPS）一起除 5-FU 之外共同刺激时，分析细胞计数和炎症细胞因子的产生。hOMK 的数量随 5-FU 刺激而显著减少，而随 β-cry 处理而增加。hOMK 中白细胞介素（IL）-6、IL-8、基质金属蛋白酶（MMP）-2 和 MMP-9 的 mRNA 表达以及 IL-6 和 IL-8 的蛋白产生在 5-FU 刺激下增加。同时，β-cry 处理显著抑制 IL-8 和 MMP-9 的 mRNA 表达，并诱导 5-FU 刺激下 IL-8 的产生。LPS 和 5-FU 的共同刺激增强了 hOMK 中 IL-6 和 IL-8 的产生。β-cry 可以增强细胞增殖，并抑制 5-FU 诱导的 hOMK 中炎症细胞因子和 MMP 的表达。因此，β-cry 可以缓解化疗引起的口腔黏膜炎的症状，其与口腔护理联合使用对口腔黏膜炎的管理有效。
