Progressive peritoneal fibrosis, membrane hyperpermeability, and ultrafiltration failure have been observed in patients on long-term peritoneal dialysis (PD). The present study tested the hypothesis that reactive oxygen species (ROS) generated by conventional PD solution (PDS) mediate functional and structural alterations of peritoneal membrane in vivo. Sprague-Dawley rats were randomized to control, PDS, PDS with an antioxidant, and PDS with an angiotensin II (Ang II) receptor blocker. Commercial PDS containing 3.86% glucose (20-30 ml) with or without N-acetylcystein (NAC) 10 mM or losartan 5 mg/kg was administered intraperitoneally twice a day for 12 weeks. Control rats received sham injection. Rats treated with PDS had significantly lower drain volume and D(4)/D(0) glucose, but higher D(4)/P(4) creatinine and increased membrane thickness and endothelial NOS (eNOS) expression compared to control rats. Omental transforming growth factor (TGF)-beta1, vascular endothelial growth factor (VEGF), collagen I, and heat-shock protein (hsp) 47 expression and lipid peroxide levels and dialysate VEGF and Ang II concentrations were significantly increased in rats treated with PDS compared to control. All of these changes were prevented by both NAC and losartan. In conclusion, the present study demonstrates that ROS generated by conventional PDS are, in large part, responsible for peritoneal fibrosis and membrane hyperpermeability. We suggest that antioxidants or Ang II receptor blockers may allow better preservation of the structural and functional integrity of the peritoneal membrane during long-term PD.

ABSTRACT:In this study, the antibacterial substances ZnO, organic acids and a bacteriophage cocktail were added to the diet of weanling pigs to evaluate the effects on gut health. Dietary treatments were basal diet without any supplementation (Control) and basal diet either supplemented with 0.34% (2500 ppm) ZnO, 0.20% organic acids or with 0.10% bacteriophage cocktail. Faecal score was decreased in ZnO and bacteriophage cocktail treatments. The total number of ileal anaerobic bacteria, Bifidobacterium spp. and Lactobacillus spp. were higher in ZnO, bacteriophage cocktail and organic acids, while ileal coliforms and caecal Clostridium spp. were decreased in comparison to Control. Faecal coliforms (Day 7 and Day 21) and Clostridium spp. (Day 21 and Day 35) were lower in bacteriophage cocktail. The gain to feed ratio was improved in all supplemented groups. The digestibility of dry matter was increased at the end of the experiment in all supplemented groups, while that of crude protein was increased only at Day 21 in bacteriophage cocktail. Duodenal villus height was increased in ZnO and bacteriophage cocktail. Bacteriophage cocktail also showed a greater villus height in the small intestine. Supplementation of bacteriophage cocktail in weaning pig diets resulted in better growth performance, digestibility and gut development compared to Control, and thus, it can be concluded that its effects are comparable to ZnO or organic acids supplementation.