title: Pyrrolidine dithiocarbamate reduces lung injury caused by mesenteric ischemia/reperfusion in a rat model.
abstract: BACKGROUND
  Pyrrolidine dithiocarbamate (PDTC) is a low-molecular thiol antioxidant and potent inhibitor of nuclear factor-kappaB (NF-kappaB) activation. It has been shown to attenuate local harmful effects of ischemia/reperfusion (I/R) injury in many organs. In this study, we aimed to study the effect of PDTC on lung reperfusion injury induced by superior mesenteric occlusion.
  
  
  METHODS
  Male Wistar-albino rats randomized into three groups: (1) sham-operated control group (n = 12), laparotomy without I/R injury; (2) intestinal ischemia/reperfusion (I/R) group (n = 12), 60 min of ischemia by superior mesenteric occlusion followed by 2 h of reperfusion; and (3) I/R+PDTC-treated group (n = 12), 100 mg/kg injection of PDTC intravenously, 30 min after the commencement of reperfusion. Evans blue dye was injected to half of rats in all groups before the induction of I/R. We assessed the degree of pulmonary tissue injury biochemically by measuring malondialdehyde (MDA), glutathione (GSH), and nitric oxide (NO) levels, and histopathologically by establishing pulmonary neutrophil sequestration and acute lung injury scoring. Pulmonary edema was evaluated by Evans blue dye extravasation, as well as lung tissue wet/dry weight ratios.
  
  
  RESULTS
  Pyrrolidine dithiocarbamate treatment significantly reduced the MDA and NO levels, and increased the GSH levels in the lung parenchyma, biochemically (p < 0.05), and atteneuated the pulmonary parenchymal damage, histopathologically (p < 0.05). However, pulmonary neutrophil sequestration was not affected by postischemic treatment with PDTC (p > 0.05). Pyrrolidine dithiocarbamate administration also significantly alleviated the formation of pulmonary edema, as evidenced by the decreased Evans blue dye extravasation and organ wet/dry weight ratios (p < 0.05).
  
  
  CONCLUSIONS
  This study showed that postischemic treatment with PDTC significantly attenuated the lung reperfusion injury. Further clinical studies are needed for better understanding of the specific mechanisms of PDTC protection against I/R-related organ injury and to clarify whether PDTC may be a useful therapeutic agent during particular operations where remote organ I/R injury occurs.
authors.affiliation: Department of General Surgery, Pamukkale University, School of Medicine, 20070, Denizli, Turkey.
authors.forename: Burhan
authors.initials: B
authors.lastname: Kabay
authors.forename: Zafer
authors.initials: Z
authors.lastname: Teke
authors.forename: Faruk Onder
authors.initials: FO
authors.lastname: Aytekin
authors.forename: Cigdem
authors.initials: C
authors.lastname: Yenisey
authors.forename: Ferda
authors.initials: F
authors.lastname: Bir
authors.forename: Mustafa
authors.initials: M
authors.lastname: Sacar
authors.forename: Ergun
authors.initials: E
authors.lastname: Erdem
authors.forename: Akin
authors.initials: A
authors.lastname: Ozden
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002199:Capillary Permeability / Q000187:drug effects*; D004195:Disease Models, Animal; D005978:Glutathione / Q000032:analysis; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000032:analysis; D008641:Mesenteric Vascular Occlusion; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000473:pathology; D009566:Nitrates / Q000032:analysis; D009573:Nitrites / Q000032:analysis; D011654:Pulmonary Edema / Q000473:pathology / Q000517:prevention & control*; D011759:Pyrrolidines / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D013859:Thiocarbamates / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D009566:Nitrates; D009573:Nitrites; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D008315:Malondialdehyde; D005978:Glutathione