The effects of low-dose erythropoiesis-stimulating agents on peritoneal fibrosis induced by chemical peritonitis and on peritoneal tissue MMP-2 and TIMP-2 Levels in rats.
OBJECTIVE
The objective of the present study was to investigate the effect of low-dose erytropoesis-stimulating agents (ESA) on the development of peritoneal fibrosis in chlorhexidine gluconate-induced peritoneal sclerosing rats and to assess the peritoneal tissue levels of MMP-2 and TIMP-2, which may be regarded as factors in the development of peritoneal fibrosis.


METHODS
Twenty-four Wistar albino rats were divided into three groups. The control group received 0.9% saline (3 ml/d) intraperitoneally, the CH group received 3 ml daily injections of 0.1% chlorhexidine gluconate (CH) intraperitoneally, and the CH+ESA group received 3 ml daily injections of 0.1% CH intraperitoneally and epoetin beta (3 x 20 IU/kg/week) subcutaneously. On the twenth-first day, rats were sacrificed, and parietal peritoneum samples were obtained from the left anterior abdominal wall. Pathological samples were examined using Hematoxyline & Eosin (HE) stains. The thickness, vascular proliferation, and inflammation were determined by light microscopy. MMP-2 and TIMP-2 were studied immunohistochemically by monoclonal antibody staining.


RESULTS
Inflammation, vascular proliferation, and fibrotic area percentages were not statistically significant between groups. Histopathologically control, CH, CH+ESA groups peritoneal thickness were 8.02 +/- 2.89, 146.74 +/- 26.1, and 48.12 +/- 16.8 micrometers, respectively. The decrease in thickness of parietal peritoneum in CH+ESA group was statistically significant when compared to CH. Immunohistochemically, interferon was shown to decrease MMP-2 expression on parietal peritoneum than group CH, but has no effect on TIMP-2.


CONCLUSIONS
Low-dose ESA histopatologically reduces peritoneal fibrosis induced by chlorhexidine gluconate. However, from dosage and duration points of view, we need extended clinical and experimental studies.
Mustafa Kemal University Faculty of Medicine, Department of Histology and Embryology, Hatay, Turkey. yildirima31@yahoo.com.tr
Ayse
A
Yildirim
Orhan Veli
OV
Ozkan
Ahmet
A
Aslan
Zikret
Z
Koseoglu
Ali
A
Borazan
D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002710:Chlorhexidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006397:Hematinics / Q000494:pharmacology*; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism*; D056627:Peritoneal Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010538:Peritonitis / Q000139:chemically induced; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D018709:Statistics, Nonparametric; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000187:drug effects / Q000378:metabolism*
D015415:Biomarkers; D006397:Hematinics; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; C010882:chlorhexidine gluconate; D002710:Chlorhexidine