Is the pathobiology of chemotherapy-induced alimentary tract mucositis influenced by the type of mucotoxic drug administered?
Is the pathobiology of chemotherapy-induced alimentary tract mucositis influenced by the type of mucotoxic drug administered?
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DOI：
10.1007/s00280-008-0732-8
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发表时间：
2009-01-01
影响因子：
3
通讯作者：
Keefe, Dorothy M. K.
中科院分区：
文献类型：
--
作者：
Logan, Richard M.;Stringer, Andrea M.;Keefe, Dorothy M. K.
目的消化道粘膜炎是癌症治疗中的一个严重问题，但其病理机制仍不完全清楚。核因子-κ B（NF-κ B）和促炎细胞因子在其发生发展中起重要作用。先前已在使用暗Agglutinin大鼠的动物模型中，在伊立替康给药后AT的不同部位中证明了这一点。本研究的目的是确定是否发生在AT的变化是由mucotoxic drug.Methods的类型的影响雌性DA大鼠给予单剂量的甲氨蝶呤（1.5 mg/kg肌肉注射）或5-氟尿嘧啶（150 mg/kg腹腔注射）。分别于30、60、90 min、2、6、12、24、48和72 h处死大鼠。对照组大鼠未接受治疗。收集口腔粘膜、空肠和结肠样品。苏木精-伊红染色，免疫组化法检测NF-κ B、TNF、IL-1 β和IL-6的表达。结果MTX和5-FU均可引起AT组织损伤，NF-κ B和特异性促炎细胞因子表达改变。然而，这项研究表明，有不同的组织学变化的时间，以及时间和强度的促炎细胞因子的组织表达所造成的不同drugs.Conclusions从这项研究的结果表明，有不同的药物引起的粘膜炎的病理生物学。这可能对粘膜炎的管理具有重要的影响，特别是关于粘膜炎治疗方案的开发。需要进一步的调查，以确定导致不同药物造成损害的确切途径。
Purpose Alimentary tract ( AT) mucositis is a serious problem complicating cancer treatment, however, its pathobiology remains incompletely understood. Nuclear factor-kappa B(NF-kappa B) and pro-inflammatory cytokines are considered to have important roles in its development. This has been previously demonstrated in different sites of the AT following administration of irinotecan in an animal model using the Dark Agouti rat. The aim of the present study was to determine whether the changes that occur in the AT are affected by the type of mucotoxic drug.Methods Female DA rats were given a single dose of either methotrexate (1.5 mg/kg intramuscularly) or 5-fluorouracil (150 mg/kg intraperitoneally). Rats were killed at 30, 60, 90 min, 2, 6, 12, 24, 48 and 72 h. Control rats received no treatment. Samples of oral mucosa, jejunum and colon were collected. Haematoxylin and eosin stained sections were examined with respect to histological evidence of damage and standard immunohistochemical techniques were used to demonstrate tissue expression of NF-kappa B, TNF, IL-1 beta and IL-6.Results Both MTX and 5-FU administration caused histological evidence of tissue damage in the AT as well as changes in tissue expression of NF-kappa B and specific pro-inflammatory cytokines. This study, however, demonstrated that there were differences in the timing of histological changes as well as the timing and intensity of pro-inflammatory cytokine tissue expression caused by the different drugs.Conclusions The results from this study suggest that there are differences in the mucositis pathobiology caused by different drugs. This may have important ramifications for the management of mucositis particularly with respect to the development of treatment regimens for mucositis. Further investigations are required to determine the exact pathways that lead to damage caused by the different drugs.