title: Effects of pyrrolidine dithiocarbamate on healing of colonic anastomoses in the cecal ligation and puncture model of intraperitoneal sepsis in rats.
abstract: BACKGROUND
  Pyrrolidine dithiocarbamate (PDTC) is a low-molecular thiol antioxidant and potent inhibitor of nuclear factor-kappaB (NF-kappaB) activation. In recent animal studies, the delaying effect of intraperitoneal sepsis on healing of colonic anastomoses has been demonstrated. In this study, we aimed to investigate the effects of PDTC on healing of colonic anastomoses in the presence of intraperitoneal sepsis induced by a rodent model of cecal ligation and puncture (CLP).
  
  
  METHODS
  Anastomosis of the left colon was performed on the day following CLP in 30 rats that were divided into three groups: sham-operated control (laparotomy and cecal mobilization, group I, n =10), cecal ligation and puncture (CLP) (group II, n = 10), PDTC-treated group (100 mg/kg IV before construction of the colonic anastomosis) (group III, n = 10). On postoperative day 6, all animals were sacrificed, and anastomotic bursting pressures were measured in vivo. Tissue samples were obtained for further investigation of colonic anastomotic hydroxyproline (HP) contents, perianastomotic myeloperoxidase (MPO) activity, and malondialdehyde (MDA) and glutathione (GSH) levels.
  
  
  RESULTS
  There was a statistically significant increase in the activity of MPO and MDA levels in the CLP group (group II) along with a decrease in GSH levels, colonic anastomotic HP contents, and bursting pressure values when compared to controls (group I). However, PDTC treatment led to a statistically significant increase in the tissue HP contents, GSH levels, and colonic anastomotic bursting pressure values, along with a decrease in MPO activity and MDA levels in group III (p < 0.05).
  
  
  CONCLUSIONS
  This study showed that PDTC treatment significantly prevented the delaying effect of CLP-induced intraperitoneal sepsis on anastomotic healing in the colon. Further clinical studies are needed to clarify whether PDTC may be a useful therapeutic agent to increase the safety of the anastomosis during particular operations where sepsis-induced injury occurs.
authors.affiliation: Department of General Surgery, Pamukkale University Faculty of Medicine, 20070, Kinikli, Denizli, Turkey. zteke_md@yahoo.com
authors.forename: Zafer
authors.initials: Z
authors.lastname: Teke
authors.forename: Faruk Onder
authors.initials: FO
authors.lastname: Aytekin
authors.forename: Cagatay
authors.initials: C
authors.lastname: Aydin
authors.forename: Burhan
authors.initials: B
authors.lastname: Kabay
authors.forename: Cigdem
authors.initials: C
authors.lastname: Yenisey
authors.forename: Suzan
authors.initials: S
authors.lastname: Sacar
authors.forename: Nilufer Genc
authors.initials: NG
authors.lastname: Simsek
authors.forename: Koray
authors.initials: K
authors.lastname: Tekin
mesh_terms: D000714:Anastomosis, Surgical; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002432:Cecum / Q000601:surgery; D004195:Disease Models, Animal; D005978:Glutathione / Q000032:analysis; D008026:Ligation; D015227:Lipid Peroxidation; D008297:Male; D010532:Peritoneal Diseases / Q000503:physiopathology*; D011677:Punctures; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000503:physiopathology*; D013859:Thiocarbamates / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D005978:Glutathione