Abstract | PURPOSE: METHODS: 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. RESULTS:
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. CONCLUSIONS: 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.
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Authors | Pedro M G Soares, Roberto C P Lima-Junior, José Maurício S C Mota, Priscilla F C Justino, Gerly Anne C Brito, Ronaldo A Ribeiro, Fernando Q Cunha, Marcellus H L P Souza |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 68
Issue 3
Pg. 713-20
(Sep 2011)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 21153821
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antimetabolites, Antineoplastic
- Cytokines
- Ginkgolides
- Lactones
- Platelet Activating Factor
- ginkgolide B
- Peroxidase
- Receptors, Platelet-Derived Growth Factor
- Fluorouracil
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Topics |
- Animals
- Antimetabolites, Antineoplastic
(toxicity)
- Cytokines
(metabolism)
- Duodenum
(metabolism)
- Fluorouracil
(toxicity)
- Ginkgolides
(pharmacology)
- Intestinal Diseases
(chemically induced, pathology)
- Intestinal Mucosa
(pathology)
- Lactones
(pharmacology)
- Leukocyte Count
- Leukopenia
(blood, chemically induced)
- Mice
- Mice, Inbred BALB C
- Mice, Knockout
- Mucositis
(chemically induced, pathology)
- Peroxidase
(metabolism)
- Platelet Activating Factor
(antagonists & inhibitors, genetics, physiology)
- Receptors, Platelet-Derived Growth Factor
(genetics)
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