Abstract
Background and objectives: 5-Fluorouracil (5-FU) is a commonly used drug for the treatment of malignant cancers. Approximately 80% of patients undergoing 5-FU treatment suffer from gastrointestinal mucositis. The aim of this study was to investigate the effect of chamomile extract on the pathogenesis of 5-FU induced intestinal mucositis in Albino rat.Materials and methods: In current study forty females Albino rats, weighing 220-280 g were used in the study. For the induction of mucositis, 60 mg/kg of 5-FU was administered intraperitoneally to each animal in the study group on day 0, and 40 mg/kg was administered on day 2. The control animals were intraperitoneally injected by normal saline in the same manner and dose like 5-FU on day 0 and 2. Then the rats in each group were randomly divided into two groups: Distilled water treated group and chamomile extract treated group (10 animals each).A volume of distilled water equal to chamomile extract was given by intragastric gavage tube, while the other group was gavaged with chamomile extract at a dose of (100 mg/ kg) two times daily. The treatment with distilled water or the chamomile extract was initiated on day 5 and the experiment continues for twelve days. The body weight for each rat was measured and then the animals were sacrificed on day 8 and 12 (five animals each). In each experiment, one centimeter of proximal jejunum was removed for histopathological, intestinal morphometry, and immunohistochemical analysis using Ki-67 and Bcl-2 immunolabeling.Results: Chamomile can protect the jejunum from fluorouracil-induced cytotoxicity and attenuate or decrease the associated injury. The chamomile in 5-FU/chamomile group causes significant increase in villi length, crypt depth, number of goblet cells, and Ki-67 and Bcl-2 immunexpression in comparison with 5-FU/water group at day 8. But longer duration of taking chamomile can cause cytotoxic and damaging effect to the jejunum. Conclusion: Chamomile can protect the jejunum from fluorouracil-induced mucositis, it attenuate the associated injury if it taken for short duration, but the reverse was occurred if it taken for longer period.
Highlights
Mucositis, referred to as mucosal barrier injury, is one of the most debilitating side effects of chemotherapy treatment, characterized by inflammation, mucosal ulceration, and intestinal permeability which is probably due to villous atrophy [1]
Chamomile can protect the jejunum from fluorouracil-induced mucositis, it attenuate the associated injury if it taken for short duration, but the reverse was occurred if it taken for longer period
Attention has been drawn towards the pathophysiology and clinical symptoms of intestinal mucositis [3], which is characterized by symptoms like nausea, bloating, vomiting, abdominal pain, and severe diarrhea [4,5]
Summary
Referred to as mucosal barrier injury, is one of the most debilitating side effects of chemotherapy treatment, characterized by inflammation, mucosal ulceration, and intestinal permeability which is probably due to villous atrophy [1]. Mucositis is associated with bacteremia, malnutrition, and the use of total parenteral nutrition. These complications all lead to longer hospitalizations and increasing health care costs. According to the model introduced by Sonis, five phases are important in the pathophysiology of mucositis: The formation of reactive oxygen species leading to the activation of nuclear factor kappa B (NFκB) during the initiation phase, the induction of messenger molecules such as tumor necrosis factor alpha (TNFα), resulting in treatment-related tissue inflammation and apoptosis during the up regulation/message generation phase, the amplification of messenger molecules in the amplification/signaling phase, leading to more inflammation and apoptosis, discontinuity of the epithelial barrier resulting from apoptosis during the ulcerative phase, thereby promoting bacterial translocation, and a spontaneous healing phase, characterized by cell proliferation [1]
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