The efficacy of irbesartan and spironolactone in preventing peritoneal fibrosis in rats

VIII - SUMMARY There are increasing efforts on prevention of peritoneal fibrosis in peritoneal dialysis patients, which may lead to treatment failure. Recently it has been realised that renin angiotensin and aldosterone system has antifibrotic effects on myocardium, kidney and vascular structures independent from its hemodynamic effects. In the present experimental study, we aimed to research the effects of an angiotensin II receptor antagonist (irbesartan) and an aldosteron antagonist (spironolactone) in prevention of peritoneal fibrosis. Forty wistar rats were randomised into 5 groups. I: Bacteria-Cytodex (B), II: Bacteria- Irbesartan (BI), III: Bacteria-Spironolactone (BS) IV: Bacteria-Irbesartan-Spironolactone (BIS) and V: Control(K). All groups except the control group were given bacteria-Cytodex suspension intraperitoneally (IP). First group was not given any medication. Irbesartan (100mg/kg, orally) and spironolactone (50mg/kg, orally) were administered to BI and BS groups respectively. Both medication were given simultaneously to BIS group at the same doses and by the same routes, whereas only Cytodex was administered to group K. At 8th day rats were undergone laparotomy and the degree of peritoneal adhesion was scored. Before sacrification, peritoneal washing fluid, blood and peritoneal tissue samples were obtained. Peritoneal tissue samples taken from three standard regions (liver, intestine and anterior abdominal wall) were stained with H&E and Masson's-Tri chrome and examined under light microscopy. Three areas from each peritoneal regions were assessed. Peritoneal thickness was measured and inflammation, fibrosis were assessed semi-quantitatively. Transforming growth factor-Bl (TGF-131), procollagen type I C-propeptide (PICP), procollagen type III N- propeptide (PIIINP) levels were measured in serum and peritoneal washing fluid samples. Peritoneal total adhesion score was significantly higher in group B than that of the group K. (p<0.01). Whereas it was lower in BI and BIS groups than group B (p<0.01). And it was lower in BS group than B group;however p was at the borderline (p=0.06). Mean peritoneal thickness, mean inflammation and mean fibrosis scores were significantly higher in group B in comparison to group K. Mean peritoneal thickness score of all treatment groups (BI, BS,BIS) were significantly lower when compared to that of group B. However, mean inflammation and mean fibrosis scores did not differ significantly. Total adhesion score, mean peritoneal thickness, mean inflammation and mean fibrosis scores were found to be positively correlated with each other. Peritoneal washing fluid TGF-B1 levels were similar in all groups. However serum TGF-Ö1 levels were significantly higher in group B than they were in group K. On the other hand, serum TGF-61 levels were significantly lower in groups BI and BS 39when compared to that of the group B. Peritoneal lavage fluid PICP and PIIINP levels and serum PIIINP levels were similar in all groups. Serum PICP levels in BI and BIS groups were significantly different than group B. In a conclusion, although biochemical data are not statistically significant in our study, histopathological data demonstrates that irbesartan and spironolactone decrease the peritoneal injury due to bacterial peritonitis. But, neither irbesartan nor spironolactone is superior to each other in decreasing peritoneal injury and the concominant administration of them does not have additive effect. On the other hand, we put forward that angiotensin II related mechanisms also play an important role in peritoneal injury related with bacterial peritonitis. Therefore, irbesartan and spironolactone can be used for the prevention of peritoneal injury. 40