Beneficial effects of nutritional supplements on intestinal epithelial barrier functions in experimental colitis models in vivo

Acute and chronic colitis affect a huge proportion of the population world-wide.The etiology of colitis cases can be manifold,and diet can significantly affect onset and outcome of colitis.While many forms of acute colitis are easily treatable,chronic forms of colitis such as ulcerative colitis and Crohn’s disease(summarized as inflammatory bowel diseases)are multifactorial with poorly understood pathogenesis.Inflammatory bowel diseases are characterized by exacerbated immune responses causing epithelial dysfunction and bacterial translocation.There is no cure and therapies aim at reducing inflammation and restoring intestinal barrier function.Unfortunately,most drugs can have severe side effects.Changes in diet and inclusion of nutritional supplements have been extensively studied in cell culture and animal models,and some supplements have shown promising results in clinical studies.Most of these nutritional supplements including vitamins,fatty acids and phytochemicals reduce oxidative stress and inflammation and have shown beneficial effects during experimental colitis in rodents induced by dextran sulphate sodium or 2,4,6-trinitrobenzene sulfonic acid,which remain the gold standard in pre-clinical colitis research.Here,we summarize the mechanisms through which such nutritional supplements contribute to epithelial barrier stabilization.

Renin-angiotensin system blockade: Effect on renal mRNA expression in 5/6 nephrectomized rats

The aim of this study was to determinate the gene expression levels of angiotensinogen, angiotensin converting enzyme, renin, (pro)renin receptor, and the final rennin-angiotensin system (RAS) products Angiotensin (Ang) II and Ang 1-7 inthe remnant kidney of 5/6 nephrectomized rats and its response to RAS pharmacological blockade. Male Wistar rats were divided into five groups: sham operated (SO), 5/6 nephrectomized (NFX), NFX + captopril (50 mg/ kg/day), NFX + losartan (10 mg/kg/day), and NFX + aliskiren (10 mg/kg/day). Animals were followed up for 60 days and protein urine excretion was measured. Systolic blood pressure, renal tissue RAS mRNA expression levels, plasma Ang II, and plasma Ang 1-7 were evaluated at day 60 after nephrectomy. Blood pressure and urine protein were increased after 5/6 nephrectomy. Ang II levels were increased 9.4 fold, whereas Ang 1-7 decreased 72.9% in NFX animals compared with SO rats. 5/6 nephrectomy increased renal angiotensinogen and (pro)renin receptor mRNA expression but down-regulated renin mRNA expression. RAS blockade restored the systolic blood pressure to normal values and slowed down urinary protein excretion, and also prevented changes in Ang II and Ang 1-7. RAS blockade reduced (pro)renin receptor, ACE, and AGT mRNA expression in the remnant kidney. However, renin mRNA expression increased compared with NFX rats. In conclusion these results suggest that inhibition of Ang II synthesis by RAS blockade is associated with renal regulation of RAS mRNA expression and this may be through a mechanism related with the Ang II/Ang 1-7 balance.