title: The changes induced by cyclophosphamide in intestinal barrier and microflora in mice.
abstract: Infection is one of the most commonly encountered complication during chemotherapy treatment, and recent studies showed that such infections are aroused primarily from the intestinal microflora through bacterial translocation. We aimed to investigate the alterations of mucosal barrier and colonization resistance in mouse treated with cyclophosphamide (CTX) to further understand the translocation mechanism. Male Balb/c mice were administered intraperitoneally with CTX at 25 mg/kg, 50 mg/kg and 100 mg/kg for 5 days. We found that pretreatment with CTX, especially at high dose, increased the potentially pathogenic bacteria counts (Escherichia coli, enterobacteraceae, Pseudomonas and enterococci) and the intestinal permeability, which was associated with the reduction of tight junctions and adherens junctions. Our results suggested that disruption of mucosal barrier and colonization resistance may be partly responsible for the bacterial translocation during chemotherapy. Thus, modulation of mechanical mucosal barrier and colonization resistance might represent a new opportunity for applications in cancer patients to reduce infectious complications.
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
authors.forename: Kai-xiong
authors.initials: KX
authors.lastname: Liu
authors.forename: Jie-ming
authors.initials: JM
authors.lastname: Qu
authors.forename: Xiao-dan
authors.initials: XD
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015820:Cadherins / Q000378:metabolism; D003520:Cyclophosphamide / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D007422:Intestines / Q000187:drug effects* / Q000382:microbiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D064307:Microbiota / Q000187:drug effects*; D062793:Occludin / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D062793:Occludin; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D003520:Cyclophosphamide
keywords: Bacterial translocation; Cyclophosphamide; Intestinal microflora; Tight junction