Effects of Systemic Dexamethasone Premedication on Experimental Oral Mucositis

OBJECTIVES: Oral Mucositis (OM) is a common complication of cytotoxic cancer therapy. One of the major molecular events underlying the overlapping phases of OM development is activation of Nuclear Factor-KappaB (NF-kB) transcription factor and its leading pro-inflammatory cytokines. To investigate how suppression of NF-kB and its gene products affects the course and severity of OM, a potent corticosteroid was administered before chemotherapy and along the course of an experimentally-induced OM.

METHODS: 75 male adult golden hamsters were randomly divided into five groups (n=15). Control animals received no medication. The other four groups received 5-Fluorouracil on days 1-2 one hour after daily injections of either normal saline or Dexamethasone (DEX) in three dosages, continuing till the 9th day. Along 16 days of experimental period to cover OM resolution, all the animals were blindly subjected to scratching by needle tips over cheek pouches on day 4 to potentiate OM, macroscopic assessments on days 6, 9, 16 and microscopic assessments in animals killed on days 9, 16 using valid scoring systems, and blood sampling for microbiologic culture on two randomly selected animals from each group on day 9. The data were analyzed using Kruskal-Wallis test.

RESULTS: Comparison of the groups in macroscopic and microscopic OM scores showed a highly protective role of DEX premedication at high and moderate dosages (p<0.001). The unfortunate outcome of our trial was mortality, mostly seen in the group taking high DEX dosage (n=3), with sepsis as the most likely cause as proposed by blood culture.

CONCLUSION: Our findings confirmed the evidence for critical role of NF-kB and its leading processes on OM development at phases before surface epithelial denudation. In the course of the current chemotherapeutic regimens using steroids, whether a protective effect against the intervening OM like that of our experiment exists remains to be established.