title: Role of granulocyte colony-stimulating factor in paclitaxel-induced intestinal barrier breakdown and bacterial translocation in rats.
abstract: BACKGROUND
  Chemotherapy causes breakdown of the intestinal barrier, which may lead to bacterial translocation. Paclitaxel, an anti-tubulin agent, has many side effects; however, its effect on the intestinal barrier is unknown. Previous studies show that granulocyte colony-stimulating factor (G-CSF) plays an important role in modulating intestinal barrier function, but these studies are not conclusive. Here, we investigated the effects of paclitaxel on the intestinal barrier, and whether G-CSF could prevent paclitaxel-induced bacterial translocation.
  
  
  METHODS
  Twenty-four male Sprague-Dawley rats were divided into three groups: control group, paclitaxel group and paclitaxel + G-CSF group. Intestinal permeability was measured by the urinary excretion rates of lactulose and mannitol administered by gavage. The mesenteric lymph nodes, spleen and liver were aseptically harvested for bacterial culture.Endotoxin levels and white blood cell (WBC) counts were measured and bacterial quantification performed using relative real-time PCR. Jejunum samples were also obtained for histological observation. Intestinal apoptosis was evaluated using a fragmented DNA assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate(dUTP)-biotin nick end-labeling staining. One-way analysis of variance and Fisher's exact test were used to compare differences between groups.
  
  
  RESULTS
  Paclitaxel induced apoptosis in 12.5% of jejunum villus cells, which was reduced to 3.8% by G-CSF treatment.Apoptosis in the control group was 0.6%. Paclitaxel treatment also resulted in villus atrophy, increased intestinal permeability and a reduction in the WBC count. G-CSF treatment resulted in increased villus height and returned WBC counts to normal levels. No bacterial translocation was detected in the control group, whereas 6/8, 8/8, and 8/8 rats in the paclitaxel group were culture-positive in the liver, spleen and mesenteric lymph nodes, respectively. Bacterial translocation was partially inhibited by G-CSF.
  
  
  CONCLUSIONS
  Paclitaxel disrupts the intestinal barrier, resulting in bacterial translocation. G-CSF treatment protects the intestinal barrier, prevents bacterial translocation, and attenuates paclitaxel-induced intestinal side-effects.
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Yang-guang
authors.initials: YG
authors.lastname: Xu
authors.forename: Xue-ning
authors.initials: XN
authors.lastname: Duan
authors.forename: Yin-hua
authors.initials: YH
authors.lastname: Liu
authors.forename: Jian-xin
authors.initials: JX
authors.lastname: Zhao
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Jing-ming
authors.initials: JM
authors.lastname: Ye
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018988:Bacterial Translocation / Q000187:drug effects*; D004731:Endotoxins / Q000097:blood; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D017239:Paclitaxel / Q000494:pharmacology*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004731:Endotoxins; D016179:Granulocyte Colony-Stimulating Factor; D017239:Paclitaxel