(P21-015-24) Orally-Administered Emu Oil Reduces Proximal Colonic Crypt Hyperplasia in a Murine Model of Colitis-Associated Colorectal Cancer

Objectives: Emu Oil (EO) has demonstrated protective and reparative properties in preclinical models of bowel disease, including colitis-associated colorectal cancer (CA-CRC). However, its potential to reduce colonocyte proliferation and inhibit CA-CRC progression is undetermined. We hypothesized that orally-administered EO would reduce colonocyte proliferation in a mouse model of CA-CRC.

Methods: Female C57BL/6 mice were injected with saline or azoxymethane (7.4mg/kg, intraperitoneal) followed by ad libitum access to either water or three dextran sulphate sodium (DSS)/water cycles (each cycle comprising seven days DSS [2%w/v] and 14 days water). Mice (n=9/group) were orally-administered either water (80μL) or EO (low 80μL or high 160μL dose), thrice weekly for nine weeks. Proximal and distal colonic sections were stained with haematoxylin and eosin for crypt depth, cell count and size measurements and immunohistochemically-stained to determine the proliferation marker Ki-67 in upper and lower colonocyte crypt zones. p< 0.05 was considered statistically significant.

Results: In the proximal colon, numbers of Ki-67-positive cells in the upper and lower crypt regions of CA-CRC mice were increased by up to 100% compared with normal controls; low dose EO significantly decreased Ki-67-positive cells by 47% (p < 0.05) compared with CA-CRC controls. Numbers of Ki-67-positive cells in the distal colon increased only in the upper crypt region in CA-CRC controls compared with normal mice (157%), with no further impact following EO administration (p >0.05). Proximal and distal colonic crypt depth increased in mice with CA-CRC (20% and 37%, respectively; p< 0.01), with greater distal colonocyte count, compared with normal controls (37%; p< 0.05). EO did not impact colonic crypt depth nor cell counts in normal or CA-CRC mice (p >0.05). Furthermore, proximal colonocyte count, proximal and distal colonic cell diameter and number of cells per 100μm remained unchanged among treatment groups (p >0.05).

Conclusions: Low dose EO attenuated proximal colonic crypt cell proliferation in mice with CA-CRC. Importantly, crypt depth and proliferation in normal mice remained unchanged following EO treatment, supporting its safety for long-term use to treat intestinal disorders.

Funding Sources: The author(s) received no funding for this research.