Effects of the tumour necrosis factor-alpha inhibitors pentoxifylline and thalidomide in short-term experimental oral mucositis in hamsters.
Oral mucositis is a frequent side-effect of cancer therapy. A definitive method of prophylaxis or treatment is not yet available. As pentoxifylline (PTX) and thalidomide (TLD) have been shown to inhibit cytokine synthesis, we studied the effects of these cytokine inhibitors in an experimental oral mucositis model. Oral mucositis was induced in Golden hamsters by the administration of 5-fluorouracil (5-FU) followed by mechanical trauma of the cheek pouch. On days 4, 5, 10, 12, 14 and 16, lesions induced by 5-FU were examined macroscopically and microscopically, and the presence and intensity of hyperemia, erythema, edema, inflammatory cell infiltration, hemorrhagic areas, ulcers and abscesses were recorded. Saline (control), PTX (5, 15, 45 mg kg(-1)) or TLD (10, 30, 90 mg kg(-1)) were administered daily and animals were killed on day 10 for macroscopic and histological analysis and assay of myeloperoxidase (MPO) activity. Animals were weighed daily, and total and differential leukocyte counts were performed on peripheral blood. PTX and TLD were found to reduce the macroscopic and histological parameters of oral mucositis and MPO activity. PTX and TLD also reversed peripheral neutrophilia, but only PTX prevented weight loss. The results indicate a protective effect of PTX and TLD, suggesting an important role for tumour necrosis factor-alpha (TNF-alpha) in the pathophysiology of 5-FU induced-oral mucositis in hamsters.
Lima
V
V
Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Rua Coronel Nunes de Melo 1127, Rodolfo Teófilo-CEP 60430-270, Fortaleza, Ceará, Brazil.
Brito
G A C
GA
Cunha
F Q
FQ
Rebouças
C G
CG
Falcão
B A A
BA
Augusto
R F
RF
Souza
M L P
ML
Leitão
B T
BT
Ribeiro
R A
RA
D000038:Abscess / Q000473:pathology; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects; D006224:Cricetinae; D004195:Disease Models, Animal; D004487:Edema / Q000473:pathology; D004890:Erythema / Q000473:pathology; D005472:Fluorouracil / Q000009:adverse effects; D006470:Hemorrhage / Q000473:pathology; D006940:Hyperemia / Q000473:pathology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007958:Leukocyte Count; D008297:Male; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D019226:Oral Ulcer / Q000473:pathology; D010431:Pentoxifylline / Q000627:therapeutic use*; D009195:Peroxidase / Q000032:analysis / Q000187:drug effects; D020011:Protective Agents / Q000627:therapeutic use; D013280:Stomatitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D013792:Thalidomide / Q000627:therapeutic use*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000964:Antimetabolites, Antineoplastic; D007166:Immunosuppressive Agents; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D009195:Peroxidase; D010431:Pentoxifylline; D005472:Fluorouracil