Department of Otorhinolaryngology-Head and Neck Surgery, Dongguk University Ilsan Hospital, College of Medicine, Goyang, Republic of Korea.
Sensory Organ Research Institute, College of Medicine, Dongguk University, Gyengju, Republic of Korea.
In Vivo. 2023 Jan-Feb;37(1):218-224. doi: 10.21873/invivo.13070.
BACKGROUND/AIM: This study aimed to develop a reliable chemotherapy-induced oral mucositis (CIOM) rat model by intraperitoneally administering a single dosage of 5-fluorouracil (5-FU) combined with a chemical stimulus.
The 5-FU dosage for CIOM development was determined by the survival rate of rats administrated 160 mg/kg, 200 mg/kg, and 240 mg/kg of 5-FU. Thirty rats were assigned to normal control (NC) and three experimental groups: i) ulcer formation without 5-FU administration (PBS/U+), ii) 5-FU administration without ulcer formation (5-FU/U-), and iii) ulcer formation after 5-FU administration (5-FU/U+). White blood cell count and weight were measured at the day of 5-FU administration (D0), ulcer formation (D2), and two days after ulcer formation (D4). The oral mucosa for histologic evaluations was obtained two (D4) and five days (D7) after ulcer formation.
The 5-FU dosage for CIOM development was 200 mg/kg. White blood cell count (WBC) counts and weight of rats were significantly lower in 5-FU/U- (WBC, p<0.001; weight, p=0.002) and 5-FU/U+ (WBC, p<0.001; weight, p<0.001) groups compared to those in the NC group at D4. The number of Ki-67 positive cells in the oral epithelium was lower in 5-FU/U+ group compared to that in NC (p<0.001) and PBS/U+ (p=0.047) groups at D7.
Single administration of 200 mg/kg of 5-FU combined with a chemical stimulus can lead to an immune-suppressive status, failure of weight gain, and impairment of epithelium regeneration as observed in a CIOM rat model.
背景/目的:本研究旨在通过腹腔内单次给予 5-氟尿嘧啶(5-FU)并联合化学刺激来建立可靠的化疗诱导性口腔黏膜炎(CIOM)大鼠模型。
通过观察给予 160mg/kg、200mg/kg 和 240mg/kg 5-FU 的大鼠的存活率来确定用于 CIOM 发展的 5-FU 剂量。将 30 只大鼠分为正常对照组(NC)和三个实验组:i)未给予 5-FU 的溃疡形成组(PBS/U+),ii)未形成溃疡的 5-FU 给予组(5-FU/U-),和 iii)给予 5-FU 后形成溃疡的组(5-FU/U+)。在给予 5-FU 的当天(D0)、溃疡形成时(D2)和溃疡形成后两天(D4)测量白细胞计数和体重。在溃疡形成后两天(D4)和五天(D7)获取口腔黏膜进行组织学评估。
用于 CIOM 发展的 5-FU 剂量为 200mg/kg。与 NC 组相比,5-FU/U-(白细胞计数,p<0.001;体重,p=0.002)和 5-FU/U+(白细胞计数,p<0.001;体重,p<0.001)组大鼠在 D4 时的白细胞计数(WBC)和体重明显更低。与 NC 组和 PBS/U+组相比,5-FU/U+组在 D7 时口腔上皮中 Ki-67 阳性细胞的数量更低(p<0.001)。
单次给予 200mg/kg 的 5-FU 并联合化学刺激可导致免疫抑制状态、体重增加失败和上皮再生受损,这与 CIOM 大鼠模型中的观察结果一致。