October 3, 2018
Castro-Lopex J, Teles M, Fierro C, et al. Pilot study: duodenal MDR1 and COX2 gene expression in cats with inflammatory bowel disease and low-grade lymphoma. J Feline Med Surg. 2018 Aug;20(8):759-766.
Cats can develop chronic enteropathies and two of the most common causes of this condition are inflammatory bowel disease (IBD) and low-grade alimentary lymphoma (LGAL). The underlying causes of either form are unknown though IBD is theorized to be due to multifactorial mechanisms. LGAL is the most common form of lymphoma in cats.
In humans, multidrug resistance 1 (MDR1) gene encodes a protein implicated in intestinal transport of substrates like bacterial products and drugs from inside to outside of cells, therefore likely implicated in IBD pathogenesis and resistance to treatment. Cyclooxygenase 2 (COX2) is an inflammatory enzyme that can be induced in several situations such as by cellular activation, proinflammatory cytokines, growth factors, tumor promoters and prostaglandin mediation. In spite of the importance of MDR1 and COX2, changes in their messenger RNA (mRNA) levels have not been studied in cats with IBD or LGAL. This pilot study was performed to determine their particular mRNA levels and evaluate how they correspond with clinical signs, histological severity and between genes.
This pilot study included cats diagnosed with IBD (n=20) and LGAL (n=9) between 2008 and 2015. The study also included three healthy cats as part of a healthy control group where endoscopy was performed just prior to ovariohysterectomy. All were duodenal intestinal samples obtained by endoscopy. The median age for the IBD group was approximately 10 years, the LGAL group had a median age of almost 12 years. The most common clinical sign in the cats was weight loss (94%), then vomiting (81%), lethargy and inappetence (71%) and diarrhea (68%). In clinical laboratory values, the LGAL group were more likely to demonstrate hypoproteinemia, hypoalbuminemia and hypocobalanemia.
In evaluating results of the study, the authors noted a statistically significant difference for MDR1 and COX2 mRNA levels between the IBD and LGAL groups. They did not determine a correlation between molecular gene expression, feline chronic enteropathy activity index and histological grading for IBD, and between MDR1 and COX2 genes. There was a positive statistically significant correlation observed between both gene expressions in the duodenum of cats.
The authors conclude from the study that MDR1 and COX2 gene expression is increased in cats with low-grade alimentary lymphoma compared to those diagnosed with IBD. The healthy control group had lower values than the two disease groups. The results suggest these genes may be part of the pathogenesis of IBD or LGAL in cats. More cats with IBD would have been needed as part of the study to differentiate them into food-responsive or steroid-responsive groups. Additional evaluation is necessary to understand the role of MDR1 and COX2 in resistance to treatment and prognosis in cancer cases as well as those with IBD. (VLT)