Discipline of Physiology, Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia.
Department of Gastroenterology, Women's and Children's Hospital, North Adelaide, South Australia, Australia.
Carcinogenesis. 2021 Feb 25;42(2):202-209. doi: 10.1093/carcin/bgaa099.
Ulcerative colitis is an incurable condition whereby patients are at an increased risk of developing colorectal cancer (CRC). We aimed to investigate the combination of Emu oil (EO) and grape seed extract (GSE) in an azoxymethane (AOM)/dextran sulphate sodium (DSS) model of colitis-associated CRC (CA-CRC). C57BL/6 mice (n = 10/group) were injected i.p. with saline or AOM (7.4 mg/kg) and underwent three DSS/water cycles. Mice were orally-gavaged thrice weekly with water (80 μl), EO (80 μl), GSE (80 μl; 400 mg/kg) or combined EO/GSE (160 μl). Mice were euthanized on day 63. AOM/DSS induced significant bodyweight loss (max -21%) and increased disease activity index (DAI) (max +83%) throughout the trial (P < 0.05). EO (max -53%), GSE (max -51%) and EO/GSE (max -71%) reduced DAI scores in AOM/DSS mice in all DSS cycles (P < 0.05). EO/GSE-treatment in AOM/DSS mice resulted in further DAI reduction compared with EO (max -62%) and GSE (max -71%) alone (P < 0.05). AOM/DSS mice presented with severe colonoscopically-assessed colitis at all time-points, which was reduced by EO, GSE and EO/GSE (P < 0.05). EO, GSE and EO/GSE reduced the number of colonic tumours compared with AOM/DSS controls (P < 0.05). Myeloperoxidase (acute inflammation) and fluorescein isothiocyanate-dextran levels (intestinal permeability) were increased in AOM/DSS controls (P < 0.05). EO (-58%) and EO/GSE (-77%) reduced fluorescein isothiocyanate-dextran compared with AOM/DSS controls (P < 0.05), with no effect on myeloperoxidase. Histologically-assessed severity scores were increased in the distal colon of AOM/DSS mice compared with saline (P < 0.05), with no effect observed following treatment. The combination of EO and GSE improved clinical indicators and reduced colonic tumours in AOM/DSS treated mice, suggesting potential in CA-CRC management.
溃疡性结肠炎是一种无法治愈的疾病,患者罹患结直肠癌(CRC)的风险增加。我们旨在研究鸸鹋油(EO)和葡萄籽提取物(GSE)在氧化偶氮甲烷(AOM)/葡聚糖硫酸钠(DSS)诱导的结肠炎相关结直肠癌(CA-CRC)模型中的联合作用。将 C57BL/6 小鼠(每组 10 只)腹腔注射生理盐水或 AOM(7.4 mg/kg),并进行三次 DSS/水循环。每周三次通过口服给予小鼠水(80 μl)、EO(80 μl)、GSE(80 μl;400 mg/kg)或 EO/GSE 联合(160 μl)。在第 63 天处死小鼠。AOM/DSS 诱导显著的体重减轻(最大 -21%)和疾病活动指数(DAI)增加(最大 +83%)在整个试验过程中(P < 0.05)。EO(最大 -53%)、GSE(最大 -51%)和 EO/GSE(最大 -71%)降低了 AOM/DSS 小鼠在所有 DSS 周期中的 DAI 评分(P < 0.05)。与 EO(最大 -62%)和 GSE(最大 -71%)单独治疗相比,EO/GSE 治疗 AOM/DSS 小鼠导致 DAI 进一步降低(P < 0.05)。AOM/DSS 小鼠在所有时间点均表现出严重的结肠内镜评估结肠炎,EO、GSE 和 EO/GSE 降低了结肠炎的严重程度(P < 0.05)。与 AOM/DSS 对照组相比,EO、GSE 和 EO/GSE 降低了结肠肿瘤的数量(P < 0.05)。AOM/DSS 对照组的髓过氧化物酶(急性炎症)和荧光素异硫氰酸酯葡聚糖水平(肠通透性)升高(P < 0.05)。与 AOM/DSS 对照组相比,EO(-58%)和 EO/GSE(-77%)降低了荧光素异硫氰酸酯葡聚糖的水平(P < 0.05),对髓过氧化物酶没有影响。与生理盐水相比,AOM/DSS 小鼠的远端结肠组织学评估严重程度评分升高(P < 0.05),但治疗后无影响。EO 和 GSE 的联合应用改善了 AOM/DSS 治疗小鼠的临床指标并减少了结肠肿瘤,提示其在 CA-CRC 管理中的潜在作用。