POSSIBILITY OF ORALLY ADMINISTERED L-LYSINE-A-OXIDASE INTERNALIZATION IN THE MODEL OF ISOLATED CUT OF RAT SMALL INTESTINE

Abstract

Enzyme L-lysine а-oxidase (LO) exhibits significant antitumor effects by parenteral administration and is promising for clinical trials, particularly in the case of colorectal cancer. The fungi Trichoderma cf.aureoviride Rifai VKM F-4268D is a source of LO. Since there is evidence in the literature of oral use of proteins for therapeutic purposes, it seemed promising to investigate the possibility of such administration route for LO. The goal of the work was to determine the ability of LO to be internalized by the rat small intestine. LO was labeled by Ac-ridinium (LO-Acridinium). Experiments were performed on the rat model using isolated inverted segments of small intestine. The inverted segments were immersed into incubation medium, containing LO-Acridinium. After 30 minutes the samples were taken from the incubation medium and from the intestine segments and relative luminescence was determined by standard flash luminescence method. The amount of absorbed LO-Ac-ridinium was estimated to be 11% for the entire length of the small rat intestine. Based on the optimal total parenteral dose of 400 U/kg for mice the total dose when administered orally was estimated as 4000 U/kg. The absorption of LO through the wall of the rat small intestine was quantitatively characterized, the possibility of its oral administration was proved, and the oral therapeutic dose for mice was estimated.