Protein fraction of Calotropis procera latex protects against 5-fluorouracil-induced oral mucositis associated with downregulation of pivotal pro-inflammatory mediators.
Naunyn Schmiedebergs Arch Pharmacol
; 385(10): 981-90, 2012 Oct.
Article
en En
| MEDLINE
| ID: mdl-22797601
ABSTRACT
Oral mucositis is an important dose-limiting and costly side effect of cancer chemotherapy. Soluble proteins obtained of the latex of Calotropis procera have been extensively characterized as anti-inflammatory in different experimentally induced inflammatory conditions, including arthritis and sepsis. In this study, the phytomodulatory laticifer proteins (LP) were challenged to regress the inflammatory events associated with 5-fluorouracil-induced oral mucositis. We also evaluated the expression of pro-inflammatory cytokines and inducible enzymes, such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Oral mucositis was induced in hamsters by two injections of 5-fluorouracil (5-FU; 60 and 40 mg/kg, i.p., on experimental days 1 and 2, respectively). LP (5 mg/kg, i.p.) was injected 24 h before and 24 h after mechanical trauma of the cheek pouches. A normal control group received only saline. On day 10, the animals were sacrificed, and the cheek pouches were excised for macroscopic and histopathological analysis, myeloperoxidase activity measurement, and immunohistochemical assessment of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), iNOS, and COX-2. LP significantly inhibited macroscopic histopathological scores and myeloperoxidase activity compared with the 5-FU control group. 5-Fluorouracil also induced marked immunostaining of TNF-α, IL-1ß, iNOS, and COX-2 on inflamed conjunctive and epithelial tissue compared with the normal control group. Such damage was significantly inhibited (p < 0.05) by LP treatment compared with the 5-FU group. These findings demonstrate an anti-inflammatory effect of LP on 5-FU-induced oral mucositis. The protective mechanism appears to involve inhibition of the expression of iNOS, COX-2, TNF-α, and IL-1ß.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas de Plantas
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Estomatitis
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Calotropis
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Fluorouracilo
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Factores Inmunológicos
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Látex
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Antimetabolitos Antineoplásicos
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Naunyn Schmiedebergs Arch Pharmacol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Brasil