Mitochonic acid-5 ameliorates chlorhexidine gluconate-induced peritoneal fibrosis in mice

The aim of this study is to assess the influence of darbepoetin on the development of peritoneal fibrosis in rats induced by Chlorhexidine gluconate (0.1%) and ethanol (15%) and to determine the effect on peritoneal tissue levels of MMP–2 and TIMP–2, possible important factors in progression of peritoneal fibrosis. Twenty-four female Wistar albino rats were divided into three groups. The first group (CH group) received 3 ml/200g daily intraperitoneal injections of Chlorhexidine gluconate (0.1%) and ethanol (15%) dissolved in saline to induce chemical peritonitis; group 2 (ESA group) received 3 ml/200g daily injections of Chlorhexidine gluconate (0.1%) and ethanol (15%) dissolved in saline and also darbepoetin 12.5 microgr/ per kilogram/ day subcutaneously on the first and seventh days; group 3 (Control group) received intraperitoneal 0.9% saline (3 ml/200g/d) through the right lower quadrant by 21 gauge needle. The study duration was fourteen days. On the fifteenth day rats were sacrificed, parietal peritoneum samples were obtained from the left anterior abdominal wall. Pathological samples were examined using Hematoxyline & Eosin (HE) stains. The thickness, vasculpathy, and inflammation were determined by light microscopy. MMP-2 and TIMP-2 were studied immunohistochemically by monoclonal antibody staining. The activity of MMP-2 on peritoneal tissue was studied by gelatin zymography and TIMP–2 protein level was analysed by ELISA, biochemically. The decrease in thickness of parietal peritoneum in group ESA was statistically significant when compared to CH group (p<0.05). Inflammation scores, and vascularization score surfaces were not statistically different between these groups (p>0.05). Immunohistochemically, darbepoetin was shown to decrease MMP-2 expression on parietal peritoneum in CH group (p<0.05), but had no effect on TIMP-2 (p>0.05). Biochemically the ratio of active MMP–2 to proMMP–2 was more significantly increased in the ESA group than in the CH group (p<0.001), however, TIMP- 2 levels in both groups were decreased compared to the control group (p<0.05). Darbepoetin histopathologically reduced peritoneal fibrosis induced by Chlorhexidine gluconate. We can suggest that Darbepoetin does not cause peritoneal fibrosis and may prevent peritoneal fibrosis in rats possibly related to an effect on MMP-2 expression. Further research regarding the utility and dosage should be considered.

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Vitamin D Can Ameliorate Chlorhexidine Gluconate-Induced Peritoneal Fibrosis and Functional Deterioration through the Inhibition of Epithelial-to-Mesenchymal Transition of Mesothelial Cells

BioMed Research International ◽

10.1155/2015/595030 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

Yi-Che Lee ◽

Shih-Yuan Hung ◽

Hung-Hsiang Liou ◽

Tsun-Mei Lin ◽

Chu-Hung Tsai ◽

...

Keyword(s):

Vitamin D ◽

Epithelial To Mesenchymal Transition ◽

Mesothelial Cells ◽

Chlorhexidine Gluconate ◽

Functional Evaluation ◽

Peritoneal Fibrosis ◽

Mesenchymal Transition ◽

Functional Deterioration ◽

E Cadherin

Background. Peritoneal dialysis (PD) can induce fibrosis and functional alterations in PD patients’ peritoneal membranes, due to long-term unphysiological dialysate exposure, partially occurring via triggering of epithelial-to-mesenchymal transition (EMT) in peritoneal mesothelial cells (MCs). Vitamin D can ameliorate these negative effects; however, the mechanism remains unexplored. Therefore, we investigated its possible links to MCs EMT inhibition.Methods. Peritoneal fibrosis was established in Sprague-Dawley rats by chlorhexidine gluconate (CG) intraperitoneal injection for 21 days, with and without 1α,25(OH)2D3treatment. Morphological and functional evaluation and western blot analysis of EMT marker were performed upon peritoneum tissue.In vitrostudy was also performed in a primary human peritoneal MC culture system; MCs were incubated with transforming growth factor-β1 (TGF-β1) in the absence or presence of 1α,25(OH)2D3. EMT marker expression, migration activities, and cytoskeleton redistribution of MCs were determined.Results. 1α,25(OH)2D3ameliorated CG-induced morphological and functional deterioration in animal model, along with CG-induced upregulation ofα-SMA and downregulation of E-cadherin expression. Meanwhile, 1α,25(OH)2D3also ameliorated TGF-β1-induced decrease in E-cadherin expression, increase in Snai1 andα-SMA expression, intracellular F-actin redistribution, and migration activityin vitro.Conclusion. 1α,25(OH)2D3can ameliorate CG-induced peritoneal fibrosis and attenuate functional deterioration through inhibiting MC EMT.

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