Pyrrolidine dithiocarbamate prevents deleterious effects of remote ischemia/reperfusion injury on healing of colonic anastomoses in rats.
BACKGROUND
Pyrrolidine dithiocarbamate (PDTC) is a low-molecular-weight 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 recent animal studies, a delaying effect of remote organ I/R injury on the healing of colonic anastomoses has been demonstrated. In this study we investigated whether PDTC prevents harmful systemic effects of superior mesenteric I/R on left colonic anastomosis in rats.


METHODS
Anastomosis of the left colon was performed in 40 rats randomly allocated into the following four groups: (1) Sham-operated group (group I, n = 10)-simultaneously with colonic anastomosis, the superior mesenteric artery and collateral branches divided from the celiac axis and the inferior mesenteric artery were isolated but not occluded. (2) Sham+PDTC group (group II, n = 10)-identical to sham-operated rats except for the administration of PDTC (100 mg/kg IV bolus) 30 minutes prior to commencing the experimental period. (3) I/R group (group III, n = 10)-60 minutes of intestinal I/R by superior mesenteric artery occlusion. (4) PDTC-treated group (group IV, n = 10)-PDTC 100 mg/kg before and after the I/R. On postoperative day 6, all animals were sacrificed, and anastomotic bursting pressures were measured in vivo. Tissue samples were obtained for investigation of anastomotic hydroxyproline (HP) contents, perianastomotic malondialdehyde (MDA) levels, myeloperoxidase activity (MPO), and glutathione (GSH) level.


RESULTS
There was a statistically significant decrease in anastomotic bursting pressure values, tissue HP content and GSH level, along with an increase in MDA level and MPO activity in group III, when compared to groups I, II, and IV (p < 0.05). However, PDTC treatment led to a statistically significant increase in anastomotic bursting pressure values, tissue HP content and GSH level, along with a decrease in MDA level and MPO activity in group IV (p < 0.05).


CONCLUSIONS
This study showed that PDTC treatment significantly prevented the delaying effect of remote organ I/R injury on anastomotic healing in the colon. Further clinical studies are needed to clarify whether PDTC may be a useful therapeutic agent for increasing the safety of the anastomosis during particular operations where remote organ I/R injury occurs.
Teke
Zafer
Z
Department of General Surgery, Pamukkale University, Faculty of Medicine, 20070, Kinikli, Denizli, Turkey. zteke_md@yahoo.com.
Aytekin
Faruk Onder
FO
Department of General Surgery, Pamukkale University, Faculty of Medicine, 20070, Kinikli, Denizli, Turkey.
Kabay
Burhan
B
Department of General Surgery, Pamukkale University, Faculty of Medicine, 20070, Kinikli, Denizli, Turkey.
Yenisey
Cigdem
C
Department of Biochemistry, Adnan Menderes University, Faculty of Medicine, 09100, Aydin, Turkey.
Aydin
Cagatay
C
Department of General Surgery, Pamukkale University, Faculty of Medicine, 20070, Kinikli, Denizli, Turkey.
Tekin
Koray
K
Department of General Surgery, Pamukkale University, Faculty of Medicine, 20070, Kinikli, Denizli, Turkey.
Sacar
Mustafa
M
Department of Cardiovascular Surgery, Pamukkale University, Faculty of Medicine, 20070, Kinikli, Denizli, Turkey.
Ozden
Akin
A
Department of General Surgery, Pamukkale University, Faculty of Medicine, 20070, Kinikli, Denizli, Turkey.
D000714:Anastomosis, Surgical / Q000009:adverse effects / Q000379:methods; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003106:Colon / Q000098:blood supply / Q000737:chemistry / Q000601:surgery*; D003108:Colonic Diseases / Q000601:surgery; D004195:Disease Models, Animal; D005978:Glutathione / Q000032:analysis; D006909:Hydroxyproline / Q000032:analysis; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009195:Peroxidase / Q000032:analysis; D011759:Pyrrolidines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D013859:Thiocarbamates / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
D000975:Antioxidants; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D008315:Malondialdehyde; D009195:Peroxidase; D005978:Glutathione; D006909:Hydroxyproline