Our findings suggest that the blockade of TRPA1 attenuates visceral nociception by a mechanism independent of the modulation of resident cells, nitric oxide and opioid pathways.
Oral mucositis (OM) is a common and dose-limiting side effect of cancer treatment, including 5-fluorouracil (5-FU) and radiotherapy. The efficacy of the therapeutic measures to prevent OM is limited and disease prevention is not fully observable. Amifostine is a cytoprotective agent with a described anti-inflammatory potential. It is clinically used to reduce radiotherapy and chemotherapy-associated xerostomia. This study investigated the protective effect of amifostine on an experimental model of OM. Hamsters were divided into six groups: saline control group (5 mL/kg), mechanical trauma (scratches) of the right cheek pouch; 5-FU (60 and 40 mg/kg,
ip
, respectively, administered on days 1 and 2); amifostine (12.5, 25, or 50 mg/kg) + 5-FU + scratches. Salivation rate was assessed and the animals were euthanized on day 10 for the analysis of macroscopic and microscopic injury by scores. Tissue samples were harvested for the measurement of neutrophil infiltration and detection of inflammatory markers by ELISA and immunohistochemistry. 5-FU induced pronounced hyposalivation, which was prevented by amifostine (P<0.05). In addition, 5-FU injection caused pronounced tissue injury accompanied by increased neutrophil accumulation, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) tissue levels, and positive immunostaining for TNF-α, IL-1β, and inducible nitric oxide synthase (iNOS). Interestingly, amifostine prevented the inflammatory reaction and consequently improved macroscopic and microscopic damage (P<0.05
vs
5-FU group). Amifostine reduced inflammation and protected against 5-FU-associated oral mucositis and hyposalivation.
e14183 Background: The comprehension of the mechanisms involved in the adverse events of the cytotoxic drugs available to treat metastatic colorctal cancer (CRC) is necessary to improve their efficacy and safety. The irinotecan, fluoruracil and folinic acid (IFL) bolus regimen have as its major toxicity issue the complex and multi-mediated gastrointestinal mucositis. Nevertheless, it is difficult to obtain a reliable measurement of the intestinal abnormalities and functional consequences caused by intestinal mucositis, as almost all the clinical data available are reported on a patient symptoms-based scale analysis. Methods: With the lactulose/ mannitol permeability test as the experimental platform, we did a prospective case control study with 25 metastatic CRC patients treated with first line IFL. The primary end point was to compare (Wilcoxon test) the lactulose/ mannitol permeability test before the treatment and the same patients tests at the 15th and 29th day of the first IFL cycle. Blood samples of the same individuals were obtained before the treatment and at 15th day of their first IFL cycle to compare the ELISA serum levels of potentially involved cytokines (TNFα, IL-1β, IL-6, IL-18, IL-18bp e IL-33) (paired t-test). Results: In contrast with the pretreatment controls, the lactulose/ mannitol ratio was significantly (p<0,05) increased at the D15 and D29 in patients taking the first IFL cycle. The mannitol excretion rate was also decreased (p<0,05) at the 29th day. This abnormalities also reserve significant (p<0,05 – Spearman coeficient) correlation with the diarrhea and abdominal pain symptoms (NCI-CTC version 4.0) scale reported by the patients. Otherwise, it has not been possible to demonstrate serum levels differences of the addressed cytokines before and after the treatment. Conclusions: The lactulose/ mannitol permeability test is an objective and reliable tool to measure intestinal permeability abnormalities secondary to gastrointestinal mucositis caused by IFL to metastatic CRC patients.This non-invasive test could bring more objetctive measurement of the functional consequences of this limiting toxicity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.