Pharmacodynamic Effects And Pharmacokinetics Of Selenium-enriched Bifidobacterium Longum

Selenium (Se) is an essential trace element for animals and humans, the deficiency of which is associated with an increased incidence of some human cancers. The bioavailability and toxicity of Se are closely correlated with its chemical form. Several studies suggest that organic Se is usually less toxic and more bioavailable than inorganic Se. Bifidobacterium longum (B. longum) is a lactic acid-producing bacterium that grows naturally in the human gastrointestinal tract and defends the host against viral infection. As an anaerobe, B. longum can selectively germinate and proliferate in the hypoxic regions of solid tumors. Research showed that some microorganisms were capable of accumulating large amounts of Se and transforming inorganic Se into organic Se.In this study, we demonstrated selenium (Se) accumulation in Bifidobacterium longum strain (B. longum) and evaluated the effect of Se-enriched B. longum (Se-B. longum) on tumor growth and immune function in tumor-bearing mice. Analysis using high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) revealed that more than 99% of Se in Se-B. longum was organic Se the main component of which was selenomethionine (SeMet). In the in vivo experiments, tumor-bearing mice were orally administrated with different doses of Se-B. longum alone or combined with cyclophosphamide (CTX). The results showed that the middle and high dose of Se-B. longum significantly inhibited tumor growth. When Se-B. longum and CTX were combined, the antitumor effect was significantly enhanced and the survival time of tumor-bearing mice was prolonged. Furthermore, compared with CTX alone, the combination of Se-B. longum and CTX stimulated the activity of natural killer (NK) cells and T lymphocytes, increased the levels of interleukin-2 (IL-2) and tumor necrosis factor-a (TNF-a), and the leukocyte count of H22 tumor-bearing mice.This study investigated the pharmacokinetics of selenium (Se) and Bifidobacterium longum (B. longum) in Se-enriched B. longum (Se-B. longum). Beagle dogs were administered with different doses of Se-B. longum by gavage, and atomic fluorescence spectrometry was used to determined the concentration of serum Se, tissue distribution and excretion of Se. The results suggested that content of Se in blood was not affected obviously within the dosage and the parameters of drug metabolism could not be calculated; Se mainly distributed in liver and kidney at 2 h after administration; Se was not detected in excretion of dogs. Mice were administered with different doses of Se-B. longum by gavage, and intestinal micraflora and colonization of B. longum were studied. The results indicated that B. longum mainly colonized in cecum; most of B. longum has colonized at 12 h after administration; the quantity of B. longum increased gradually at 1 d and 7 d after administration, and the quantity of B. longum didn’t decrease at 3 d after stopping administration.