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.
Yildirim
Ayse
A
Mustafa Kemal University Faculty of Medicine, Department of Histology and Embryology, Hatay, Turkey. yildirima31@yahoo.com.tr
Ozkan
Orhan Veli
OV
Aslan
Ahmet
A
Koseoglu
Zikret
Z
Borazan
Ali
A
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