Bomfin Luana E, Braga Cíntia M, Oliveira Thais A, Martins Conceição S, Foschetti Danielle A, Santos Ana A Q A, Costa Deiziane V S, Leitão Renata F C, Brito Gerly A C
Department of Medical Sciences, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
Postgraduate Program in Morphofunctional Sciences, Department of Morphology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
Biochem Pharmacol. 2017 Dec 1;145:34-45. doi: 10.1016/j.bcp.2017.08.024. Epub 2017 Sep 1.
This study aimed to elucidate the effect of 5-fluorouracil (5-FU) on the histological aspects of the major salivary glands, salivary flow and saliva composition using an established oral mucositis model in hamsters. Oral mucositis was induced by two intraperitoneal administrations of 5-FU in two consecutive days (60 and 40mg/kg), followed by cheek pouch mucosa scratch, on day 4. The Pilocarpine-stimulated salivary flow was measured 4 and 10days after the first 5-FU injection. Salivary glands were harvested for histopathological analysis, measurement of inflammatory cells, quantification of pro-inflammatory cytokines (TNF-α and IL-1β), investigation of cell death and cell proliferation. Oxidative stress and oxidative defense system were also investigated in the salivary gland tissues using MDA (malondialdehyde), nitrite, non-protein sulfhydryl groups (NP-SH), SOD (superoxide dismutase) and CAT (catalase). In addition, the CAT and lysozyme activities and the IgA and SOD levels were evaluated in the saliva samples. 5-FU significantly reduced the pilocarpine-stimulated salivary flow rate on the 4th experimental day, associated with an increase in the SOD levels in saliva. Recovery of the salivary flow and SOD were observed on day 10, when an increase in the saliva lysozyme levels was detected. In addition, 5-FU promoted vacuolization in parotid (P) and periductal edema in submandibular (SM) gland, combined with an increase in the inflammatory cells influx, mostly observed on the 4th day in SM gland and on 4th and 10th days in P. Oxidative stress was found mostly on day 10 in SM, SL and P glands, associated with release of proinflammatory cytokines, observed in SM and SL glands, but not in P. 5-FU induces an inflammatory response in the major salivary glands, most observed ten days after its first injection, which may contribute to the major salivary glands hypofunction, leading to alterations in the salivary flow rate and composition.
本研究旨在利用已建立的仓鼠口腔黏膜炎模型，阐明5-氟尿嘧啶（5-FU）对大唾液腺组织学特征、唾液分泌量及唾液成分的影响。连续两天腹腔注射5-FU（60和40mg/kg）诱导口腔黏膜炎，于第4天对颊囊黏膜进行刮擦。在首次注射5-FU后的第4天和第10天测量毛果芸香碱刺激后的唾液分泌量。采集唾液腺进行组织病理学分析、炎性细胞计数、促炎细胞因子（TNF-α和IL-1β）定量、细胞死亡及细胞增殖研究。还使用丙二醛（MDA）、亚硝酸盐、非蛋白巯基（NP-SH）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）对唾液腺组织中的氧化应激和氧化防御系统进行了研究。此外，还评估了唾液样本中的CAT和溶菌酶活性以及IgA和SOD水平。在实验第4天，5-FU显著降低了毛果芸香碱刺激后的唾液流速，同时唾液中SOD水平升高。在第10天观察到唾液流速和SOD恢复，此时检测到唾液溶菌酶水平升高。此外，5-FU导致腮腺（P）空泡化和下颌下腺（SM）导管周围水肿，同时炎性细胞浸润增加，主要在SM腺的第4天以及P腺的第4天和第10天观察到。氧化应激主要在SM、舌下腺（SL）和P腺的第10天发现，与促炎细胞因子的释放有关，在SM和SL腺中观察到，但在P腺中未观察到。5-FU在大唾液腺中诱导炎症反应，大多在首次注射后10天观察到，这可能导致大唾液腺功能减退，进而引起唾液流速和成分改变。
