1 School of Medicine, The University of Western Australia, Perth 6150, Australia.
2 Gastroenterology Department, Women's & Children's Hospital, North Adelaide 5006, Australia.
Exp Biol Med (Maywood). 2018 Jul;243(11):945-952. doi: 10.1177/1535370218787457. Epub 2018 Jul 9.
Previously, we reported that orally administered Emu Oil (EO) increases mucosal thickness in the small intestine and colon in rodent models of chemotherapy-induced mucositis and colitis. However, it remains unclear whether mucosal thickening (crypt and villus lengthening) represents a process of normal or aberrant growth. We sought to determine if villus height (VH) and crypt depth (CD) measurements returned to normal in EO-treated rats following withdrawal of EO therapy. Dark agouti rats ( n = 8/group) were gavaged daily for 10 days with water, olive oil (OO), or EO (0.5 mL or 1 mL). Groups of rats were euthanized on days 10 and 17. Intestinal weights, lengths, VH, and CD were quantified. P < 0.05 was considered significant. On day 10, jejuno-ileum weight was increased by OO (26%) and EO (0.5 mL: 15%; 1 mL: 29%) compared to water controls ( P < 0.01), which was normalized by day 17. On days 10 and 17, jejuno-ileum length was greater in OO- (12%) and EO-treated rats (0.5 mL: 8%; 1 mL: 12%; P < 0.05), relative to water controls. On day 10, OO and EO increased ileal VH (OO: 32%; 0.5 EO: 22%; EO: 35%; P < 0.01) and CD (OO: 17%; 0.5 EO: 13%; EO: 22%) compared to water controls. Importantly, however, after withdrawal of all oils, VH and CD measurements returned to normal control values. Moreover, the VH:CD ratio (potential indicator of dysplasia) remained unchanged in all experimental groups on days 10 and 17. The restoration of normal intestinal architecture following cessation of Emu Oil therapy supports its safety for application in intestinal disorders. Impact statement Uncontrolled inflammation and intestinal proliferation can predispose to the development of colorectal cancer. In previous pre-clinical studies, we demonstrated that oral administration of Emu Oil promotes intestinal repair via stimulation of the mucosa in response to tissue injury and inflammation. Therefore, it was important to determine if Emu Oil administration did not promote the precocious development of colorectal cancer. The current study revealed that Emu Oil returned indicators of intestinal proliferation back to normal values after a period of seven days. These data strongly support the safety of Emu Oil for further studies in the context of bowel inflammation.
先前,我们报道了口服鸸鹋油(EO)可增加化疗诱导的黏膜炎和结肠炎啮齿动物模型中小肠和结肠的黏膜厚度。然而,黏膜增厚(隐窝和绒毛延长)是否代表正常或异常生长过程仍不清楚。我们试图确定在停止 EO 治疗后,接受 EO 治疗的大鼠的绒毛高度(VH)和隐窝深度(CD)测量值是否恢复正常。每天给 8 只每组的深褐色大鼠(n=8/组)灌胃水、橄榄油(OO)或 EO(0.5 毫升或 1 毫升)10 天。在第 10 天和第 17 天处死各组大鼠。定量测定肠重、肠长、VH 和 CD。P<0.05 被认为具有统计学意义。第 10 天,与水对照组相比,OO(26%)和 EO(0.5 mL:15%;1 mL:29%)增加了空肠-回肠重量(P<0.01),第 17 天恢复正常。第 10 天和第 17 天,与水对照组相比,OO-(12%)和 EO 处理大鼠(0.5 mL:8%;1 mL:12%)的空肠-回肠长度增加(P<0.05)。第 10 天,OO 和 EO 增加回肠 VH(OO:32%;0.5 EO:22%;EO:35%)和 CD(OO:17%;0.5 EO:13%;EO:22%)与水对照组相比。然而,重要的是,在所有油类停用后,VH 和 CD 测量值恢复到正常对照值。此外,在第 10 天和第 17 天,所有实验组的 VH:CD 比值(发育异常的潜在指标)保持不变。鸸鹋油治疗停止后,正常肠道结构的恢复支持其在肠道疾病中的应用安全性。