title: Thalidomide suppresses sclerosing encapsulating peritonitis in a rat experimental model.
abstract: Peritoneal dialysis is an alternative treatment of patients with end-stage renal disease. Sclerosing encapsulating peritonitis is a life-threatening complication of continuous ambulatory peritoneal dialysis. The aim of the present study was to evaluate the effect of thalidomide, which is used for the treatment of various inflammatory and autoimmune diseases, on the development of sclerosing encapsulating peritonitis induced by chlorhexidine gluconate (CG). A peritoneal fibrosis model was established using rats treated intraperitoneally with injections of CG. Thalidomide was administered orally at a dose of 100 mg/kg three times per week. When compared with CG-treated rats, thalidomide (100 mg/kg orally)-treated mice subjected to CG-induced peritoneal fibrosis experienced a significantly lower rate in the extent and severity of histological signs of peritoneal injury. Thalidomide also caused a substantial reduction of 1) the rise in myeloperoxidase activity (mucosa); 2) the expression in the tissue of TNF-alpha, IL-1beta, transforming growth factor-beta, and vascular endothelial growth factor; 3) the increase in staining (immunohistochemistry) for nitrotyrosine and for poly(ADP ribose), as well as 4) the nuclear factor-kappaB activation caused by CG in the peritoneum. Thus, thalidomide treatment reduces the degree of peritoneal fibrosis caused by CG. We propose that this evidence may help clarify the potential therapeutic actions of thalidomide in patients with peritoneal fibrosis.
authors.affiliation: Department of Internal Medicine, Messina University Hospital, School of Medicine, University of Messina, Messina, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mondello
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Concetta
authors.initials: C
authors.lastname: Crisafulli
authors.forename: Paolo
authors.initials: P
authors.lastname: Mondello
authors.forename: Michele
authors.initials: M
authors.lastname: Buemi
authors.forename: Carmelo
authors.initials: C
authors.lastname: Aloisi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D015153:Blotting, Western; D002710:Chlorhexidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D051381:Rats; D013792:Thalidomide / Q000494:pharmacology / Q000627:therapeutic use*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D020672:I-kappa B Proteins; D007166:Immunosuppressive Agents; D016328:NF-kappa B; D017392:Thiobarbituric Acid Reactive Substances; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D011064:Poly Adenosine Diphosphate Ribose; C002744:3-nitrotyrosine; D014443:Tyrosine; D013792:Thalidomide; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C010882:chlorhexidine gluconate; D002710:Chlorhexidine