Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA220

Poster Communications

Matrix effects on the intestinal concentration of maslinic acid and its effects on colonic preneoplastic lesions induced by 1,2-dimethylhydrazyne in rats

R. Moreno-González1, M. Juan1, J. Planas1

1. Bioquímica i Fisiologia, Universitat de Barcelona, Barcelona, Catalunya / Barcelona, Spain.

Maslinic acid (MA) is a pentacyclic triterpene recognized as a bioactive compound that elicits different health-protecting properties without harmful effects, standing out among others, antitumoral activity. The low oral bioavailability together with a poor intestinal absorption leads to a high concentration in the large intestine, thus favouring its potential chemopreventive activity against colon cancer. Bearing in mind the high content of MA in table olives, we aimed at studying their effect on preneoplastic lesions in rats. Therefore, male Sprague-Dawley rats (7-week-old) were randomly divided into three groups according to the treatment orally administered by gavage: a MA group that received pure MA at 10 mg/kg (n=6), an olive group that was given Arbequina table olives at 3.8 g/kg which contained MA at 8.6 mg/kg (n=6) and a control group provided only with the solvent (n=6). At one week of treatment, preneoplastic lesions were induced in the colon by three weekly injection of 1,2-dimethylhydrazine (20 mg/kg; intraperitoneally). After 49 days, overnight fasted rats were anesthetized intraperitoneally with ketamine and xylacine (90 and 10 mg/kg, respectively) and blood was withdrawn by cardiac puncture and placed in EDTA-K2 tubes. Then, the colon was excised, its content collected and the tissue fixed in formalin. MA in plasma was extracted twice with ethyl acetate and vortex-mixing, whereas the determination in colon content included Polytron grinding with methanol 80% prior to HPLC-APCI-MS analysis. Aberrant crypt foci (ACF) were counted at the light microscope at 10x magnification after staining with methylene blue. MA was not found neither in animal feed nor in plasma and colon content of the control group. In contrast, this pentacyclic triterpene was detected in plasma of the MA group at 23.4 ± 7.0 nM and olive group at 10.1 ± 2.7 nM, being measured 20 h after the last oral administration. MA when administered as pure compound reached the colon at 90.7 ± 36.9 nmol/g, whereas in the olive group was 307.3 ± 80.2 nmol/g. Rats in the control group developed ACF that were reduced in a 17.8% in the MA group and a 54.1% in the olive group. In view of the results, it can be concluded that despite similar MA doses, the antitumoral activity is higher in the rats fed with table olives than in the animals receiving the pure compound. Noteworthy, the intestinal content of MA from the group administered with olives was 3.4-times higher than in the group receiving the pure compound. The lesser bioavailability of MA from table olives favours to attain higher concentrations in the colon which elicits a higher chemopreventive activity.

Where applicable, experiments conform with Society ethical requirements