Chemotherapy-induced Gastrointestinal Mucositis Research Articles

Does Chemotherapy-Induced Gastrointestinal Mucositis Affect the Bioavailability and Efficacy of Anti-Infective Drugs?

Antimicrobial prophylaxis is increasingly being used in patients with hematological malignancies receiving high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT). However, few studies have focused on the potential impact of gastrointestinal mucositis (GI-M), a frequently observed side effect of chemotherapy in patients with cancer that affects the gastrointestinal microenvironment, on drug absorption. In this review, we discuss how chemotherapy leads to an overall loss of mucosal surface area and consequently to uncontrolled transport across the barrier. The barrier function is depending on intestinal luminal pH, intestinal motility, and diet. Another factor contributing to drug absorption is the gut microbiota, as it modulates the bioavailability of orally administrated drugs by altering the gastrointestinal properties. To better understand the complex interplay of factors in GI-M and drug absorption we suggest: (i) the longitudinal characterization of the impact of GI-M severity on drug exposure in patients, (ii) the development of tools to predict drug absorption, and (iii) strategies that allow the support of the gut microbiota. These studies will provide relevant data to better design strategies to reduce the severity and impact of GI-M in patients with cancer.

Pitfalls and novel experimental approaches to optimize microbial interventions for chemotherapy-induced gastrointestinal mucositis.

Purpose of reviewThere is a growing number of studies implicating gut dysbiosis in mucositis development. However, few studies have shed light on the causal relationship limiting translational potential. Here, we detail the key supportive evidence for microbial involvement, candidate mechanisms by which the microbiome may contribute to mucositis and emerging approaches to model host–microbe interactions with clinical relevance and translational potential.Recent findingsSynthesis of existing clinical data demonstrate that modulating the microbiome drastically alters the development and severity of mucositis, providing a strong rationale for its involvement. Review of the literature revealed potential microbiome-dependent mechanisms of mucosal injury including altered drug metabolism, bile acid synthesis and regulation of the intestinal barrier. Current studies are limited in their mechanistic insight due to cross-sectional and would benefit from longitudinal analyses and baseline phenotyping.SummaryThe causative role of the microbiome in mucositis development remains unclear. Future studies must adopt comprehensive microbial analyses with functional assessment, and utilize emerging ex-vivo models to interrogate host–microbe interactions in mucositis.

Efficacy of Azatyrosine-Phenylbutyric Hydroxamides, a Histone Deacetylase Inhibitor, on Chemotherapy-Induced Gastrointestinal Mucositis.

Gastrointestinal mucositis is a serious side effect of chemotherapy. Currently, no effective treatment exists for chemotherapy-induced mucositis, prompting the need to develop an anti-mucositis agent for use in clinics. The present study investigated whether azatyrosine-PBHA (AzP), a histone deacetylase inhibitor, has a therapeutic effect on intestinal mucosa. The results indicated that AzP did not affect the proliferation and viability of cancer cells, outcomes that are achieved by suberoylanilide hydroxamic acid (SAHA). However, AzP could decrease production of the inflammatory mediators interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor-necrosis factor-α (TNF-α). In vivo histopathological assessment showed that AzP reduced cisplatin-induced injury to the jejunum villi and triggered weight loss in the C57BL/6 mice. Immunohistochemistry (IHC) results demonstrated that mice treated with AzP also recovered from cisplatin-induced injury to the intestinal mucosa. Mechanistic in vitro study using DAVID/KEGG enrichment analysis of microarray data and confirmation by a Western blot indicated the influence of AzP on the MEK/ERK and AKT-dependent pathway. In conclusion, the study demonstrated that AzP might regulate the MEK/ERK MAPK signaling pathway to attenuate MCP-1, TNF-α, and IL-6 production and provide opportunities for the development of new anti-inflammatory drugs targeting mucositis.

Effects of simvastatin on 5-fluorouracil-induced gastrointestinal mucositis in rats.

simvastatin has pleiotropic anti-inflammatory and immunomodulatory effects potentially usefull to prevent chemotherapy-induced gastrointestinal mucositis. Studies on this are scarce. This study aimed to examine the effects of simvastatin on gastric and intestinal mucositis after 5-fluorouracil (5-FU) treatment in rats. rats weighing 270±18g were divided into two groups. The 5-FU+saline group (5-FU/SAL) rats were treated with 5-FU (50mg/kg) plus 0.9% saline orally (gavage) once daily for five days. The 5-FU+simvastatin (5-FU/SIMV) group was treated with 5-FU (50mg/kg), plus simvastatin (10mg/kg), in the same way. The rats were euthanased on the sixth day, then their stomach and intestine were photographed and removed for exams. Dosages of serum TNF-a, IL-1ß, IL-6 and histopathology were done for stomach and intestine. body-weight was significantly lower in rats treated with 5-FU+saline than the weight loss of the 5-FU/SIMV group rats. TNF-a expression was lower in 5-FU/SIMV group (172.6±18pg/ml) than in 5-FU/SAL (347.5±63pg/ml). Serum IL-1b was lower in 5-FU/SAL group (134.5±23pg/ml) than in 5-FU/SIMV (48.3±9pg/ml). Serum IL-6 was 61.8±15pg/ml in 5-FU/SIMV and 129.4±17pg/ml in 5-FU/SAL groups. These differences were significant (p<0.05). Mucosal damage in stomach and jejunum were observed in rats receiving 5-FU alone. In the stomach and jejunum, simvastatin caused significant protective effects against 5-FU-induced mucosal injury. simvastatin attenuated gastric and intestinal mucositis related to 5-FU therapeutics in animal model. These data encourage forthcoming clinical studies addressing the usefulness of statins in the prevention and treatment of gastrointestinal mucositis.

Protective effect of ursodeoxycholic acid against chemotherapy-induced mucositis.

796 Background: Gastrointestinal mucositis is a serious side effect of chemotherapy. It increases the frequency of infection, risk of bleeding, and duration of hospitalization, consequently reducing subsequent chemotherapy doses. Ursodeoxycholic acid (UDCA), which is currently used in various liver diseases, exerts direct cytoprotective effects by stabilizing membranes, inhibiting apoptosis, and acting as an antioxidant. The protective effect of UDCA against chemotherapy-induced mucositis was assessed using an in vivo animal model. Methods: Sprague-Dawley rats were randomly assigned to the following 5 groups: non-chemotherapy and vehicle; 5-fluorouracil (5-FU) and vehicle; 5-FU and 10 mg/kg/day UDCA; 5-FU and 100 mg/kg/day UDCA; and 5-FU and 500 mg/kg/day UDCA. 5-FU (400 mg/kg) or physiological saline (control) was administered by intraperitoneal injection. UDCA was orally administered 1 day before 5-FU injection for 6 days. One day after the final UDCA dose, rats were sacrificed, and the intestines were dissected for tissue sampling and laboratory analysis. Results: UDCA promoted a higher body weight recovery, decreased villus destruction, and reduced inflammatory cytokines levels, at doses of 10 and 100 mg/kg/day. Villous fusion and destruction were pronounced in the 5-FU group compared with those observed in the UDCA-treated group or controls. The jejunal villous lengths were as follows: 212.8±58.0 µm, 331.3±18.0 µm, and 310.0±112.6 µm, in the 5-FU and vehicle, 5-FU and 10 mg/kg UDCA (p = 0.006), and 5-FU and 100 mg/kg UDCA groups (p = 0.046), respectively. Real-time polymerase chain reaction (RT-PCR) showed that IL-6 and TNF-α levels decreased in the 10 mg/kg and 100 mg/kg UDCA co-administration groups. Further, myeloperoxidase activity decreased in the UDCA co-administration group. Conclusions: UDCA significantly attenuated the reduction of the height of small intestinal villi and reduced inflammatory cytokine levels, thus highlighting the potential of UDCA as a preventive agent against chemotherapy-induced gastrointestinal mucositis. The specific protective mechanisms of UDCA on the gastrointestinal tract should be determined.

Chemotherapy-driven dysbiosis in the intestinal microbiome.

Chemotherapy is commonly used as myeloablative conditioning treatment to prepare patients for haematopoietic stem cell transplantation (HSCT). Chemotherapy leads to several side effects, with gastrointestinal (GI) mucositis being one of the most frequent. Current models of GI mucositis pathophysiology are generally silent on the role of the intestinal microbiome. To identify functional mechanisms by which the intestinal microbiome may play a key role in the pathophysiology of GI mucositis, we applied high-throughput DNA-sequencing analysis to identify microbes and microbial functions that are modulated following chemotherapy. We amplified and sequenced 16S rRNA genes from faecal samples before and after chemotherapy in 28 patients with non-Hodgkin's lymphoma who received the same myeloablative conditioning regimen and no other concomitant therapy such as antibiotics. We found that faecal samples collected after chemotherapy exhibited significant decreases in abundances of Firmicutes (P=0.0002) and Actinobacteria (P=0.002) and significant increases in abundances of Proteobacteria (P= 0.0002) compared to samples collected before chemotherapy. Following chemotherapy, patients had reduced capacity for nucleotide metabolism (P=0.0001), energy metabolism (P=0.001), metabolism of cofactors and vitamins (P=0.006), and increased capacity for glycan metabolism (P= 0.0002), signal transduction (P=0.0002) and xenobiotics biodegradation (P=0.002). Our study identifies a severe compositional and functional imbalance in the gut microbial community associated with chemotherapy-induced GI mucositis. The functional pathways implicated in our analysis suggest potential directions for the development of intestinal microbiome-targeted interventions in cancer patients.

Substantial decreases in the number and diversity of microbiota during chemotherapy-induced gastrointestinal mucositis in a rat model.

Earlier, we showed in acute myeloid leukemia (AML) patients that the microbiota changes dramatically during anticancer treatment, coinciding with gastrointestinal mucositis: The commensal anaerobic populations reduce in favor of potential pathogens. Therefore, interventions targeting the microbiota during mucositis might be interesting but can better be tested in animals than in vulnerable mucositis patients. Here, we aimed to study the potential microbial changes during methotrexate (MTX)-induced gastrointestinal mucositis in a well-established rat model and to study whether this model can be used for future microbial intervention studies. After injection with MTX or saline (day 0), rats were sacrificed between days 2 and 11. Plasma citrulline level, jejunal histology, and the number and diversity of intestinal bacteria in feces (using fluorescence in situ hybridization (FISH)) were determined. Mucositis was most severe on day 4 when food intake, plasma citrulline, and villus length were the lowest, compared with controls (P < 0.0125). At the same time, MTX-treated rats showed an overall decrease (705-fold) in most bacteria (using a universal probe), compared with controls (P < 0.125). Reduced bacterial presence was related with the presence of diarrhea and a reduced villus length (rho = 0.38, P < 0.05). At day 4, there was an absolute and relative decrease of anaerobes (13-fold and -58 %, respectively) and streptococci (296-fold and -1 %, respectively) but a relative increase of Bacteroides (+49 %), compared with controls (P < 0.125). In the mucositis rat model, we found substantial decreases in the number and diversity of microbiota, resembling earlier findings in humans. The model therefore seems well suited to study the effects of different microbial interventions on mucositis, prior to performing human studies.

Mo2128 Parenteral Feeding During Methotrexate-Induced Gastrointestinal Mucositis Prevents Weight Loss in the Rat

summary Background & aims: It is unknown what feeding strategy to use to prevent weight loss in patients with chemotherapy-induced gastrointestinal mucositis. When possible, enteral nutrition is preferred to parenteral nutrition because of negative side effects. In a mucositis rat model, we demonstrated disaccharide maldigestion and fat malabsorption but up to normal absorption of glucose and amino acids upon their continuous enteral administration. We now determined the effects of four different (par) enteral feeding strategies during mucositis on body weight and intestinal recovery. Methods: From days 2 to 5 after injection with methotrexate (60 mg/kg), rats continued ad libitum enteral feeding with purified diet (AIN-93G, strategy 1), received continuous enteral feeding [forcefeeding, normal daily amounts] with glucose and amino acids (Nutriflex , strategy 2) or with standard formula (Nutrini, strategy 3), or received continuous parenteral feeding with standard formula (NuTRIflex Lipid, strategy 4). Saline-treated controls continued ad libitum purified diet. Results: From day 2 on, methotrexate-treated ad libitum-fed rats showed a reduced food intake and body weight (P < 0.05), as seen before. Most continuously enterally-fed rats (88%) were terminated early because of severe abdominal distention. Parenterally-fed rats grew similarly like controls. On day 5, the jejunum of methotrexate-treated ad libitum-fed rats showed hypertrophic crypts and a normal villus length. In contrast, parenterally-fed rats showed no increase in crypt length and a reduced villus length, compared with controls (P < 0.05). Conclusion: Continuous enteral feeding in normal daily amounts during mucositis is poorly tolerated in rats. Parenteral feeding prevents weight loss during mucositis while enteral feeding in limited amounts accelerates intestinal recovery.

Parenteral feeding during methotrexate-induced gastrointestinal mucositis prevents weight loss in the rat

Summary Background & aims It is unknown what feeding strategy to use to prevent weight loss in patients with chemotherapy-induced gastrointestinal mucositis. When possible, enteral nutrition is preferred to parenteral nutrition because of negative side effects. In a mucositis rat model, we demonstrated disaccharide maldigestion and fat malabsorption but up to normal absorption of glucose and amino acids upon their continuous enteral administration. We now determined the effects of four different (par)enteral feeding strategies during mucositis on body weight and intestinal recovery. Methods From days 2 to 5 after injection with methotrexate (60 mg/kg), rats continued ad libitum enteral feeding with purified diet (AIN-93G, strategy 1), received continuous enteral feeding [force-feeding, normal daily amounts] with glucose and amino acids (Nutriflex ® , strategy 2) or with standard formula (Nutrini ® , strategy 3), or received continuous parenteral feeding with standard formula (NuTRIflex ® Lipid, strategy 4). Saline-treated controls continued ad libitum purified diet. Results From day 2 on, methotrexate-treated ad libitum-fed rats showed a reduced food intake and body weight ( P P Conclusion Continuous enteral feeding in normal daily amounts during mucositis is poorly tolerated in rats. Parenteral feeding prevents weight loss during mucositis while enteral feeding in limited amounts accelerates intestinal recovery.

Management of Gastrointestinal Mucositis Due to Cancer Therapies in Pediatric Patients: Results of a Case Series with SAMITAL ®

Gastrointestinal mucositis is a common debilitating complication of chemotherapy and one for which there is currently no effective long-term treatment. To report our experience with the use of SAMITAL(®), a new oral suspension formulation based on the combination of three standardized extracts from Vaccinium myrtillus, Macleaya cordata fruits and Echinacea angustifolia roots in the prevention and treatment of chemotherapy-induced gastrointestinal mucositis in pediatric patients. 20 pediatric patients undergoing chemotherapy for a range of oncological conditions were followed. Patients initially received oral SAMITAL(®) to treat gastrointestinal mucositis and were then given SAMITAL(®) prophylactically to prevent recurrences with successive cycles of chemotherapy. SAMITAL(®) significantly decreased gastrointestinal mucositis grade after the first episode with a reduction of mean scores from 3.2 ± 0.7 at baseline to 0.4 ± 0.6 at the end of treatment (p < 0.001). SAMITAL(®) reduced pain, mucosal erosions, bleeding and dysphagia/feeding impairment. SAMITAL(®) improved patients' overall condition and quality of life after the first administration and lowered the need for parenteral nutrition. Importantly, it allowed chemotherapy cycles to be continued without complications. Results from this case series suggest that SAMITAL(®) may play an important role in the prevention and treatment of chemotherapy-induced gastrointestinal mucositis in children and adolescents and as such warrants investigation in controlled studies.

Continuous Enteral Administration Can Enable Normal Amino Acid Absorption in Rats with Methotrexate-Induced Gastrointestinal Mucositis 2

AbstractIt is unknown what feeding strategy to use during chemotherapy-induced gastrointestinal mucositis, which causes weight loss and possibly malabsorption. To study the absorptive capacity of amino acids during mucositis, we determined the plasma availability of enterally administered amino acids (AA), their utilization for protein synthesis, and the preferential side of the intestine for AA uptake in rats with and without methotrexate (MTX)-induced mucositis. Four days after injection with MTX (60 mg/kg) or saline (controls), rats received a primed, continuous dual-isotope infusion (intraduodenal and intravenous) of labeled L-leucine, L-lysine, L-phenylalanine, L-threonine, and L-methionine. We collected blood samples, assessed jejunal histology, and determined labeled AA incorporation in proximal and distal small intestinal mucosa, plasma albumin, liver, and thigh muscle. MTX-induced mucositis was confirmed by histology. The median systemic availability of all AA except for leucine was similar in MTX-treated rats and in controls. However, the individual availability of all AA differed substantially within the group of MTX-treated rats, ranging from severely reduced (<10% of intake) to not different from controls (>40% of intake in 5 of 9 rats). More AA originating from basolateral uptake than those originating from apical uptake were used for intestinal protein synthesis in MTX-treated rats (=420% more, P < 0.05). We conclude that continuous enteral administration can enable normal AA absorption in rats with MTX-induced mucositis. The intestine prefers basolateral AA uptake to meet its need for AA for protein synthesis during mucositis.

Reduced absorption of long-chain fatty acids during methotrexate-induced gastrointestinal mucositis in the rat

Patients with chemotherapy-induced gastrointestinal mucositis suffer from weight loss and possibly malabsorption. Since long-chain fatty acids serve important functions in the body, we aimed to determine the intestinal capacity of fat absorption in rats with and without methotrexate-induced mucositis. Four days after intravenous injection with methotrexate (60mg/kg) or saline, rats received saturated ([U-(13)C]palmitic acid) and unsaturated ([U-(13)C]linoleic acid) fatty acids dissolved in oil, either as a single bolus by oral gavage or by continuous intraduodenal infusion. We determined plasma and liver label concentrations at specific time points. We confirmed methotrexate-induced mucositis by villus atrophy using microscopy. Methotrexate treatment severely reduced the appearance of [U-(13)C]palmitic- and [U-(13)C]linoleic acid in plasma and liver, compared to controls, either when administered as a bolus or continuously (all at least-63%, P<0.05). Liver [U-(13)C]palmitic acid appearance was higher than [U-(13)C]linoleic acid appearance, either when administered as a bolus (2.8-fold, P<0.01) or continuously (5.7-fold, P<0.01). The intestinal capacity to absorb long-chain fatty acids is severely reduced in rats with methotrexate-induced mucositis. Continuous administration does not overcome this impairment. The liver takes up and/or retains mainly saturated fatty acids during mucositis.

Continuous enteral administration can overcome the limited capacity to absorb glucose in rats with methotrexate-induced gastrointestinal mucositis

Patients with chemotherapy-induced gastrointestinal mucositis often suffer from weight loss. It is not well known how to enterally feed mucositis patients, potentially experiencing malabsorption. Recently, we showed in a rat model of methotrexate (MTX)-induced mucositis that intestinal absorption of glucose in trace amounts is still intact. We now determined the quantitative capacity to absorb glucose in rats with mucositis, relative to controls. We administered a physiologically relevant amount of [1-(13)C]glucose-enriched glucose (meal size) as a bolus by oral gavage (2 g/kg once) or continuously by intraduodenal infusion (±1.9 g/(kg·h) for 5 h) to rats with MTX-induced mucositis and controls. Blood [1-(13)C]glucose concentrations were determined during the experimental period. To calculate the quantitative absorptive capacity, Steele's one-compartment model, including simultaneous intravenous infusion of [6,6-(2)H(2)]glucose, was used. After the experiment, jejunal histology and plasma citrulline concentrations were assessed. MTX-induced mucositis was confirmed by a reduction in villus length and plasma citrulline (both -57%, relative to controls, P < 0.01). When glucose was administered as a bolus, MTX-treated rats only absorbed 15% of administered glucose, compared with 85% in controls (medians, P < 0.01). Upon continuous intraduodenal glucose infusion, the median absorptive capacity for glucose in MTX-treated rats did not differ from controls (80 versus 93% of administered glucose respectively, P = 0.06). However, glucose absorption differed substantially between individual MTX-treated rats (range, 21-95%), which correlated poorly with villus length (rho = 0.54, P = 0.030) and plasma citrulline (rho = 0.56, P = 0.024). Continuous enteral administration can almost completely overcome the reduced absorptive capacity for glucose in rats with mucositis.

Anti-Inflammatory Cytokines: Important Immunoregulatory Factors Contributing to Chemotherapy-Induced Gastrointestinal Mucositis

“Mucositis” is the clinical term used to describe ulceration and damage of the mucous membranes of the entire gastrointestinal tract (GIT) following cytotoxic cancer chemotherapy and radiation therapy common symptoms include abdominal pain, bloating, diarrhoea, vomiting, and constipation resulting in both a significant clinical and financial burden. Chemotherapeutic drugs cause upregulation of stress response genes including NFκB, that in turn upregulate the production of proinflammatory cytokines such as interleukin-1β (IL-1β), Interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). These proinflammatory cytokines are responsible for initiating inflammation in response to tissue injury. Anti-inflammatory cytokines and specific cytokine inhibitors are also released to limit the sustained or excessive inflammatory reactions. In the past decade, intensive research has determined the role of proinflammatory cytokines in development of mucositis. However, a large gap remains in the knowledge of the role of anti-inflammatory cytokines in the setting of chemotherapy-induced mucositis. This critical paper will highlight current literature available relating to what is known regarding the development of mucositis, including the molecular mechanisms involved in inducing inflammation particularly with respect to the role of proinflammatory cytokines, as well as provide a detailed discussion of why it is essential to consider extensive research in the role of anti-inflammatory cytokines in chemotherapy-induced mucositis so that effective targeted treatment strategies can be developed.

Su2006 Continuous Enteral Administration Overcomes the Limited Capacity to Absorb Glucose in Rats With Methotrexate-Induced Gastrointestinal Mucositis

Background Patients with chemotherapy-induced gastrointestinal mucositis often suffer from weight loss. It is not well known how to enterally feed mucositis patients, potentially experiencing malabsorption. Recently, we showed in a rat model of methotrexate (MTX)-induced mucositis that intestinal absorption of glucose in trace amounts is still intact. We now determined the quantitative capacity to absorb glucose in rats with mucositis, relative to controls.

Progress towards the development of animal models of chemotherapy-induced gastrointestinal mucositis

Progress towards the development of animal models of chemotherapy-induced gastrointestinal mucositis

Lactose maldigestion during methotrexate-induced gastrointestinal mucositis in a rat model

Patients with chemotherapy-induced gastrointestinal mucositis suffer from anorexia, diarrhea, and stomach pain, often causing weight loss and malnutrition. When the intestinal function during mucositis would be known, a rational feeding strategy might improve the nutritional state, accelerate recuperation, and increase survival of mucositis patients. We developed a methotrexate (MTX)-induced mucositis rat model to study nutrient digestion and absorption. To determine lactose digestion and absorption of its derivative glucose during mucositis, we injected Wistar rats intravenously with MTX (60 mg/kg) or 0.9% NaCl (controls). Four days later, we orally administered trace amounts of [1-(13)C]lactose and [U-(13)C]glucose and quantified the appearance of labeled glucose in the blood for 3 h. Finally, we determined plasma citrulline level and harvested the small intestine to assess histology, myeloperoxidase level, glycohydrolase activity, immunohistochemical protein, and mRNA expression. MTX-treated rats showed profound villus atrophy and epithelial damage. During the experimental period, the absorption of lactose-derived [1-(13)C]glucose was 4.2-fold decreased in MTX-treated rats compared with controls (P < 0.01). Lactose-derived [1-(13)C]glucose absorption correlated strongly with villus length (rho = 0.86, P < 0.001) and with plasma citrulline level (rho = 0.81, P < 0.001). MTX treatment decreased jejunal lactase activity (19.5-fold, P < 0.01) and immunohistochemical protein and mRNA expression (39.7-fold, P < 0.01) compared with controls. Interestingly, MTX treatment did not affect the absorption of [U-(13)C]glucose during the experimental period. We conclude that lactose digestion is severely decreased during mucositis while glucose absorption is still intact, when supplied in trace amounts. Plasma citrulline level might be a useful objective, noninvasive marker for lactose maldigestion during mucositis in clinic.

Pro-inflammatory cytokines play a key role in the development of radiotherapy-induced gastrointestinal mucositis

BackgroundMucositis is a toxic side effect of anti-cancer treatments and is a major focus in cancer research. Pro-inflammatory cytokines have previously been implicated in the pathophysiology of chemotherapy-induced gastrointestinal mucositis. However, whether they play a key role in the development of radiotherapy-induced gastrointestinal mucositis is still unknown. Therefore, the aim of the present study was to characterise the expression of pro-inflammatory cytokines in the gastrointestinal tract using a rat model of fractionated radiotherapy-induced toxicity.MethodsThirty six female Dark Agouti rats were randomly assigned into groups and received 2.5 Gys abdominal radiotherapy three times a week over six weeks. Real time PCR was conducted to determine the relative change in mRNA expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF in the jejunum and colon. Protein expression of IL-1β, IL-6 and TNF in the intestinal epithelium was investigated using qualitative immunohistochemistry.ResultsRadiotherapy-induced sub-acute damage was associated with significantly upregulated IL-1β, IL-6 and TNF mRNA levels in the jejunum and colon. The majority of pro-inflammatory cytokine protein expression in the jejunum and colon exhibited minimal change following fractionated radiotherapy.ConclusionsPro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting.

T1308 Comparison of the Effects of Acid Antisecretory Drugs On Cancer Chemotherapy-Induced Gastrointestinal Mucositis in Rats

T1308 Comparison of the Effects of Acid Antisecretory Drugs On Cancer Chemotherapy-Induced Gastrointestinal Mucositis in Rats

Cancer Chemotherapy-induced Gastrointestinal Mucositis and Second-Generation H2-blockers

Cancer Chemotherapy-induced Gastrointestinal Mucositis and Second-Generation H2-blockers