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01.04.2007 | Original Article

Role of nitric oxide on pathogenesis of 5-fluorouracil induced experimental oral mucositis in hamster

verfasst von: R. F. C. Leitão, R. A. Ribeiro, E. A. L. Bellaguarda, F. D. B. Macedo, L. R. Silva, R. B. Oriá, M. L. Vale, F. Q. Cunha, G. A. C. Brito

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 5/2007

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Abstract

Introduction

Mucositis induced by antineoplastic drugs is an important, dose-limiting, and costly side effect of cancer therapy. Aim: To investigate the role of nitric oxide (NO) on the pathogenesis of 5-fluorouracil (5-FU)-induced oral mucositis.

Materials and Methods

Oral mucositis was induced by two intraperitoneal (i.p) administrations of 5-FU on the first and second days of the experiment (60 and 40 mg/kg, respectively) in male hamsters. Animals were treated subcutaneously with saline (0.4 ml), 1,400 W (1 mg/kg), aminoguanidine (5 or 10 mg/kg) or Nϕ-Nitro-L-Arginine Methyl Ester (L-NAME) (5, 10, or 20 mg/kg) 1 h before the injections of 5-FU and daily until sacrifice, on the tenth day. Macroscopic and histopathological analyses were evaluated and graded. Tissues from the cheek pouches were harvested for measurement of myeloperoxidase (MPO) activity, nitrite level, and immunohistochemistry for induced nitric oxide synthase (iNOS).

Results

Treatment with 1,400 W or aminoguanidine reduced macroscopic and histological parameters of oral mucositis, and reduced the inflammatory cell infiltration as detected by histopathology and by MPO activity. In contrast, the administration of L-NAME did not significantly reverse the inflammatory alterations induced by experimental mucositis. Increased NOS activity, nitrite level and immunostaining for iNOS were detected on the check pouch tissue of animals submitted to 5-FU-induced oral mucositis on the tenth day.

Conclusion

These results suggest an important role of NO produced by iNOS in the pathogenesis of oral mucositis induced by 5-FU.

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Titel: Role of nitric oxide on pathogenesis of 5-fluorouracil induced experimental oral mucositis in hamster
verfasst von: R. F. C. Leitão
R. A. Ribeiro
E. A. L. Bellaguarda
F. D. B. Macedo
L. R. Silva
R. B. Oriá
M. L. Vale
F. Q. Cunha
G. A. C. Brito
Publikationsdatum: 01.04.2007
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 5/2007
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-006-0301-y

Neu im Fachgebiet Onkologie

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Springer Medizin

Role of nitric oxide on pathogenesis of 5-fluorouracil induced experimental oral mucositis in hamster

Abstract

Introduction

Materials and Methods

Results

Conclusion

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Springer Medizin

Abstract

Introduction

Materials and Methods

Results

Conclusion

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