Role of platelet-activating factor in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice
| Autor: | Pedro Marcos Gomes Soares, Roberto C. P. Lima-Júnior, Jose Mauricio Mota, Priscilla F. C. Justino, Ronaldo A. Ribeiro, Gerly Anne de Castro Brito, Marcellus H.L.P. Souza, Fernando Q. Cunha |
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| Rok vydání: | 2010 |
| Předmět: |
Mucositis
Antimetabolites Antineoplastic Cancer Research Cancer chemotherapy Side effect Duodenum Pharmacology Toxicology Pathogenesis Lactones Leukocyte Count Mice chemistry.chemical_compound medicine Animals Receptors Platelet-Derived Growth Factor Pharmacology (medical) Intestinal Mucosa Platelet Activating Factor Receptor Peroxidase Mice Knockout Mice Inbred BALB C Platelet-activating factor business.industry Leukopenia respiratory system medicine.disease Intestinal Diseases Ginkgolides Oncology chemistry Fluorouracil Immunology Knockout mouse Cytokines lipids (amino acids peptides and proteins) business medicine.drug |
| Zdroj: | Cancer Chemotherapy and Pharmacology. 68:713-720 |
| ISSN: | 1432-0843 0344-5704 |
| DOI: | 10.1007/s00280-010-1540-5 |
| Popis: | Gastrointestinal mucositis is a common side effect of cancer chemotherapy. Platelet-activating factor (PAF) is produced during gut inflammation. There is no evidence that PAF participates in antineoplastic-induced intestinal mucositis. This study evaluated the role of PAF in 5-fluorouracil (5-FU)-induced intestinal mucositis using a pharmacological approach and PAF receptor knockout mice (PAFR(-/-)).Wild-type mice or PAFR(-/-) mice were treated with 5-FU (450 mg/kg, i.p.). Other mice were treated with saline or BN52021 (20 mg/kg, s.c.), an antagonist of the PAF receptor, once daily followed by 5-FU administration. After the third day of treatment, animals were sacrificed and tissue samples from the duodenum were removed for morphologic evaluation. In addition, myeloperoxidase activity and the cytokine concentration were measured.5-FU treatment decreased the duodenal villus height/crypt depth ratio, increased MPO activity, and increased the concentration of TNF-α, IL-1β and KC in comparison with saline-treated animals. In PAFR(-/-) mice and PAFR antagonist-treated mice, 5-FU-dependent intestinal damage was reduced and a decrease in duodenal villus height/crypt depth ratio was attenuated. However, the 5-FU-dependent increase in duodenum MPO activity was not affected. Without PAFR activation, 5-FU treatment did not increase the TNF-α, IL-1β and KC concentration.In conclusion, our study establishes the role of PAFR activation in 5-FU-induced intestinal mucositis. This study implicates treatment with PAFR antagonists as novel therapeutic strategy for this condition. |
| Databáze: | OpenAIRE |
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