Basic–Alimentary TractDown-Regulation of the Monocarboxylate Transporter 1 Is Involved in Butyrate Deficiency During Intestinal Inflammation
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Patients and Biopsies
Colonic biopsy specimens were obtained from inflamed and noninflamed mucosa of 14 patients with CD (9 women, 5 men; mean age, 36 years; range, 21–78 years) and 9 patients with UC (4 women, 5 men; mean age, 46 years; range, 30–62 years). All patients underwent colonoscopy for an active disease. At the time of the study, 9 patients were receiving steroids; 2 patients, 5-aminosalicylic acid; 2 patients, azathioprine; 1 patient, 6-mercaptopurin plus infliximab; 1 patient, cyclosporin; and 8
MCT1 Expression Is Decreased During Intestinal Inflammation
We assessed MCT1 messenger RNA (mRNA) and protein expression in segments of rat colon with DSS-induced colitis and control rats. Western blot analysis of protein lysates showed that MCT1 protein levels were significantly lower in the cecum and proximal and distal colon of rats with DSS-induced colitis in comparison with controls (P < .01) (Figure 1A, i and ii). Similarly, reverse-transcription (RT) PCR analysis showed a significant decrease in MCT1 mRNA expression in these DSS-inflamed colonic
Discussion
Butyrate is essential to the health and integrity of the colonic mucosa, and its oxidation provides 70% of the total energy requirement of colonocytes. Previous studies in active IBD and in experimental DSS-colitis have shown that intestinal inflammation specifically affects butyrate metabolism because glucose and glutamine oxidation rates are not modified.6, 7, 9, 23 The data presented in this paper indicate that inflammation does not induce a general modification in colonocyte metabolism but
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2022, Journal of Pharmaceutical SciencesCitation Excerpt :A meta-analysis of available system parameters to build a CD PBPK population demonstrated a gap in the availability of intestinal DMET expression/activity data (Alrubia et al, accepted for publication in Clinical Pharmacokinetics).11 In most previous studies on CD intestine, either mRNA assays or semi-quantitative immunoassays were employed and the protein and gene expression profiles of DMETs in CD have been reported and compared with control groups in tissue and cell lines.12,13 Several reports on the mRNA expression of solute carriers (SLCs) demonstrated upregulation of ENT1, ENT2, CNT2, PEPT1, OATP4A1 and OATP2B1 in CD, whereas ASBT, MCT1 and OCTN2 were downregulated.12,14
Supported by grants from the Ligue Nationale de Lutte contre le Cancer; the Biotechnology and Biological Sciences Research Council; and Tenovus, The Cancer Charity.
We confirm that all of the authors have no conflicts of interest to disclose.
- 1
R.T. and P.d.C. contributed equally to this work.