We evaluated the effect of 6 days of intraperitoneal saline infusion on peritoneal peroxidation and permeability in rats. Peroxidation of the peritoneum as measured by malondialdehyde concentration in the omentum was increased and there was a concomitant augmented membrane permeability to glucose and resulted in a loss of ultrafiltration. In vitro experiments with mesothelial cells showed that glycosaminoglycan chondroitin sulphate appears to act as a scavenger of free radicals and so protects the mesothelial cells against injury. Thus, in rats, supplementation of the infused saline with chondroitin sulphate reduces peroxidation of the peritoneum and prevents loss of ultrafiltration during peritoneal dialysis. These results suggest that chondroitin sulphate may be effective in preventing the deterioration of peritoneal permeability during chronic peritoneal dialysis. This beneficial effect probably derives from the scavenging of free radicals by chondroitin sulphate.
We studied the toxicity of free radicals to human mesothelial cells in vitro and to the peritoneal membrane of rats during peritoneal dialysis. Free radicals cause damage to mesothelial cells as measured by release of cytosolic markers such as 86Rb and lactate dehydrogenase. Vitamin E neutralized the toxic effect of free radicals in vitro. Human mesothelial cells exposed over 6 h to a mixture of essential and nonessential amino acids in medium are more vulnerable to the cytotoxic effect of free radicals than control cells exposed to medium alone. Cells exposed previously to glucose or glycerol are less vulnerable than controls. In rats free radicals generated intraperitoneally by a xanthine-xanthine oxidase system induce changes in peritoneal permeability similar to those observed during peritonitis: loss of ultrafiltration, increased glucose absorption from the dialysate and augmented transperitoneal loss of albumin. In addition lipids in the peritoneum became perixodated. The addition of vitamin E to the peritoneal fluid with xanthine-xanthine oxidase prevents peroxidation of lipids and the subsequent loss of ultrafiltration. Our results show that free radicals may exert a potentially toxic effect on the peritoneal membrane during peritonitis. In such circumstances the addition of free radical scavenger to the dialysis fluid may preserve intact structure and function of peritoneum.
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