RESUMO
Objective: The cafeteria diet (CD), designed as an experimental diet mimicking the obesogenic diet, may contribute to the pathogenesis of inflammatory bowel diseases (IBD). This study delves into the influence of spirulina (SP) on obesity associated with colitis in Wistar rats. Methods: The amino acids composition of SP was analyzed using HPLC-FLD. Animals were equally separated into eight groups, each containing seven animals and treated daily for eight weeks as follows: Control diet (SD), cafeteria diet (CD) group, CD + SP (500 mg/kg) and SD + SP. Ulcerative colitis was provoked by rectal injection of acetic acid (AA) (3 % v/v, 5 ml/kg b.w.) on the last day of treatment in the following groups: SD + AA, SD + AA + SP, CD + AA, and CD + AA + SP. Results: Findings revealed that UC and/or CD increased the abdominal fat, weights gain, and colons. Moreover, severe colonic alteration, perturbations in the serum metabolic parameters associated with an oxidative stress state in the colonic mucosa, defined by overproduction of reactive oxygen species (ROS) and increased levels of plasma scavenging activity (PSA). Additionally, obesity exacerbated the severity of AA-induced UC promoting inflammation marked by the overexpression of pro-inflammatory cytokines. Significantly, treatment with SP provided notable protection against inflammation severity, reduced histopathological alterations, attenuated lipid peroxidation (MDA), and enhanced antioxidant enzyme activities (CAT, SOD, and GPX) along with non-enzymatic antioxidants (GSH and SH-G). Conclusions: Thus, the antioxidant effects and anti-inflammatory proprieties of SP could be attributed to its richness in amino acids, which could potentially mitigate inflammation severity in obese subjects suffering from ulcerative colitis. These results imply that SP hold promise as a therapeutic agent for managing of UC, particularly in individuals with concomitant obesity. Understanding SP's mechanisms of action may lead novel treatment strategies for inflammatory bowel diseases and hyperlipidemia in medical research.
RESUMO
BACKGROUND: Platelet derived growth factor receptor alpha (PDGFRα) has been considered as a relevant factor in tumor proliferation, angiogenesis and metastatic dissemination. It was a target of tyrosine kinase (TK) inhibitors emerged in the therapy of diverse cancers. In colorectal cancer, the commonly used therapy is anti-epithelial growth factor receptor (EGFR). However, both RAS mutated and a subgroup of RAS wild type patients resist to such therapy. The aim of this study is to investigate PDGFRα protein expression and mutational status in colorectal adenocarcinoma and their association with clinicopathological features and molecular RAS status to provide useful information for the identification of an effective biomarker that might be implicated in prognosis and treatment prediction. METHODS: Our study enrolled 103 formalin fixed paraffin-embedded (FFPE) colorectal adenocarcinoma. PDGFRα expression was investigated by immunohistochemistry (IHC). Hotspot exon 18 of PDGFRA was studied by PCR followed by Sanger sequencing and RAS status was determined by real time quantitative PCR. Thirteen normal colon tissues were used as negative controls. RESULTS: PDGFRα staining was detected in the cytoplasm of all tissues. Low expression was observed in all normal colon mucosa. In adenocarcinoma, 45% (45/100) of cases showed PDGFRα overexpression. This overexpression was significantly associated with mutations in exon 18 (P = 0.024), RAS wild type status (P < 10-3), tumor diameter (P = 0.048), whereas there was no association with tumor side (P = 0.13) and other clinicopathological features. CONCLUSION: Overexpression of PDGFRα in adenocarcinoma suggests its potential role in tumor cells growth and invasion. The association between PDGFRα overexpression in both tumor and stromal adenocarcinoma cells with RAS wild type status suggests its potential role in anti-EGFR therapy resistance and the relevance of using it as specific or adjuvant therapeutic target.