The evaluation of pentoxyfillin regarding fibrosis and possible related indicators in rat chemical peritoniti

Introduction: Peritoneal fibrosis is a common cause for terminating Continuous Ambulatory Peritoneal Dialysis (CAPD) treatment. Treatment or prophylaxis of CAPD-related peritoneal fibrosis, is still an important matter. Excessive production of matrix has been reported to be responsible of peritoneal fibrosis. Up to now, treatment of peritoneal fibrosis in patients with CAPD remains unsatisfactory. Pentoxifylline (PTX) is a methyl xanthine derivative. A number of studies has shown that Pentoxifylline to impede the progress of skin, liver and kidney fibrosis. Objective: To determine the effect of Pentoxiphylline on chlorhexidin induced peritoneal fibrosis and; to investigate the influence of peritoneal tissue cAMP level alterations on peritoneal tissue MMP-2; MMP-9, TIMP-1, TIMP-2 balances. Method: 40 Wistar albino rats were divided into five groups. All administrations were done intraabdominally with 24 G needle for 14 days. In group 1; chemical peritonitis was formed. A mixture of %0,1 chlorhexidin (CHX) + %15 ethanol + normal saline 3 ml/ day were administered. In group 2; PTX 4mg/100 g (0,2 ml/100g) mixed with normal saline were administered 3 ml/day In group 3; to prevent peritoneal fibrosis, 3 ml mixture of %0,1 CHX + %15 ethanol + normal saline and 4mg/100 g (0,2 ml/100g) PTX were administered daily. In group 4; received a solvent including PTX that forms from 1 ml distilled water + 35 mg NaCl 3 ml/day. In group 5; was described as control group and received %0,9 NS 3 ml/day All rats were sacrificed at 15. day and samples were obtained from anterior abdominal wall for parietal peritoneum and from liver for visceral peritoneum for tissue analysis. Sections were stained with Hematoxilene & Eosine (HE) and modified Masson?s Trichrome (MT) for pathological examination. These parameters were evaluated by light microscope; 1) thickness of peritoneum (parietal and visceral peritoneum) 2) fibrosis score (parietal and visceral peritoneum) 3) angiogenesis score (parietal peritoneum) 4) inflammation score (parietal and visceral peritoneum) 5) percentage of fibrotic areas on parietal peritoneum Thicknesses and percentage of fibrotic areas were evaluated as ?m. Other score evaluations were based on staining techniques. a) proMMP-2 b) proMMP-9 c) active MMP-2 d) active MMP-9 e) TIMP-1 f) TIMP-2 g) cAMP were analysed biochemically from parietal and visceral peritoneal tissues. To measure TIMP?s ELISA; for cAMP Enzyme-linked immunoassay and for MMP?s gelatin zymography were used. TIMP?s activities were measured by ELISA; cAMP activities by Enzyme-linked immunoassay and MMP?s activities were measured by gelatin zymography. Results: There was statistically significant difference among all histopathological indicators of fibrosis between CHX and other groups ( p<0.05) on parietal peritoneum. There was also significant difference among other indicators except inflammation score for visceral peritoneum( p <0.05). Pro MMP-2 levels of parietal peritoneum in CHX group were significantly higher than the other groups ( p<0.05). When compared with the SF group there was statistically significant difference (p<0.05). However there was no statistically significant finding between CHX and CHX+PTX. There was no significant difference concerning measured active MMP-2, TIMP-1 and cAMP levels between groups (p>0.05) . TIMP-2 was measured in CHX+PTX group as significantly higher than CHX group(p<0.05). ProMMP-9 was not measured in any groups on the parietal peritoneum. Levels of proMMP-2 and proMMP-9 were determined significantly higher than other groups on visceral peritoneums of CHX group. (p<0.05). Active MMP-2 wasn?t measured except CHX group. Also active MMP-9 was not established in visceral peritoneums. Significant difference was not determined among groups about TIMP-1, TIMP-2 and c AMP. Conclusion: Fibrosis was formed with Chlorhexidin on parietal and visceral peritoneal tissue. Pentoxifylline prevented this Chlorhexidin induced fibrosis histopathologically. ProMMP-2 and proMMP-9 increment was demonstrated on both peritoneal tissues during fibrosis formation. Pentoxifylline may have a role in preventing peritoneal fibrosis on visceral peritoneum by reducing proMMP-2 and pro MMP-9 levels. Pentoxifylline may increase TIMP-2 levels for preventing parietal peritoneal fbrosis. Since there is no change in cAMP levels, it can be thought that pentoxifylline prevents peritoneal fibrosis using another pathway. Key Words: Matrix metalloproteinases (MMP?s), tissue inhibitors of matrix metalloproteinase (TIMP?s), Pentoxifylline (PTX), peritoneal fibrosis, cAMP