Effect of neomycin on amino acid uptake and on synthesis and release of lipoproteins by rat intestine

Abstract

The in vitro uptake and incorporation of amino acids into proteins and lipoproteins, and release of lipoproteins by intestinal segments of control and rats treated with neomycin or its N-methylated and N-acetylated derivatives (1 mg/10 g body weight for 8 days) was investigated. The intestine of the neomycin-treated rats contained a greater amount of water within the epithelial cells (81.6 ± 6.2% vs. 89.3 ± 6.8%, P < 0.01) and it exhibited a significantly greater uptake of amino acid radioactivity per weight of tissue proteins (1.9 ± 0.2% vs. 2.6 ± 0.3%, P < 0.001). The fraction of the amino acid radioactivity incorporated into tissue proteins was not affected by the respective treatments. The distribution of the radioactivity associated with tissue lipoproteins, however, was markedly affected by neomycin. The radioactivity of tissue low density lipoproteins (LDL) and high density lipoproteins (HDL) of the neomycin-treated rats was much lower than that of the controls. This difference could be accounted for by the release of a greater proportion of LDL and HDL radioactivity in the incubation medium. Release of LDL and HDL radioactivity was inversely related to the molecular weights of these lipoproteins. The effects of neomycin were reproduced by its N-methylated derivative which is devoid of antibiotic activity but retains the polycationic properties of neomycin. The N-acetylated derivative which is devoid of both antibiotic and polycationic properties was without effect. These findings suggest that the observed effects may be related to the polycationic properties of neomycin and that they are independent of its antibiotic activity.