muramidase and Endotoxemia

The present study aimed to investigate the effects of intestinal endotoxemia (IETM) in a rat model of aluminum neurotoxicity established by D-galactose and aluminum trichloride (AlCl3). Adult Wistar rats were administered D‑galactose and AlCl3 to create the aluminum neurotoxicity model. The learning and memory abilities of the rats were subsequently observed using a Morris water maze test and the serum levels of lipopolysaccharide (LPS), tumor necrosis factor (TNF)‑α, interleukin (IL)‑1, diamine oxidase (DAO), glutamine (Gln) and glutaminase were measured. The expression of S‑100β in the serum was detected using an enzyme‑linked immunosorbent assay. The expression levels of the amyloid β‑protein (Aβ) precursor (APP), presenilin 1 (PS1), β‑site APP‑cleaving enzyme (BACE), zona occludens protein (ZO)‑1 and Aβ 1‑40 in the brain of rats were detected via reverse‑transcription polymerase chain reaction, western blotting and immunohistochemistry. The levels of LPS, TNF‑α, IL‑1, DAO, Gln and S‑100β in serum and the mRNA and protein expression levels of APP, PS1, BACE and Aβ1‑40 in the brain were markedly increased in the model rats compared with controls. The level of glutaminase in the serum and the expression of ZO‑1 in the brain were decreased in the model rats compared with controls. IETM was present in the rat model of aluminum neurotoxicity established by D‑galactose and AlCl3 and may be important in the development of this neurotoxicity.

Topics: Aluminum; Aluminum Chloride; Aluminum Compounds; Amyloid beta-Peptides; Amyloid Precursor Protein Secretases; Animals; Aspartic Acid Endopeptidases; Blood-Brain Barrier; Chlorides; Disease Models, Animal; Endotoxemia; Galactose; Interleukin-1; Intestinal Mucosa; Intestines; Lipopolysaccharides; Male; Memory; Muramidase; Neurotoxins; Peptide Fragments; Presenilin-1; Rats, Wistar; RNA, Messenger; Tumor Necrosis Factor-alpha; Zonula Occludens-1 Protein

Endotoxemia is considered to be associated with the high mortality of gram-negative septic patients. Increasing evidence shows that beta-lactam antibiotics have a propensity to induce endotoxin release from the bacterial outer membrane while killing bacteria. We have recently found that egg white lysozyme (EW-LZM) shows strong inhibition of beta-lactam induced bacteriolysis and lipopolysaccharide (LPS) release from Escherichia coli O111, resulting in reduction of the LPS-initiated inflammatory response. In this study, we compared the effect of EW-LZM on E. coli J5, which possesses rough-type LPS (RaLPS), in order to demonstrate the effect of O-antigenic polysaccharide on endotoxin neutralizing activity of EW-LZM and on inhibition of beta-lactam induced lysis by LZM. Both of the beta-lactam induced bacterial lysis and subsequent LPS release were almost completely inhibited by EW-LZM. The effect was more potent than that of wild-type LPS as assessed by released LPS concentration and LPS induced cytokine syntheses. In addition, EW-LZM was effective against lethal infection of E. coli J5 in cyclophosphamide induced leukopenic mice. These facts strongly suggested that O-antigenic polysaccharide negatively modulates LPS neutralizing activity of EW-LZM.

Topics: Animals; Anti-Bacterial Agents; Bacteriolysis; Carrageenan; Cell Line; Cyclophosphamide; Disease Models, Animal; Endotoxemia; Endotoxins; Escherichia coli; Escherichia coli Infections; Galactose; Lactams; Leukopenia; Lipopolysaccharides; Macrophages; Male; Mice; Mice, Inbred ICR; Monokines; Muramidase; O Antigens