Pyrrolidine dithiocarbamate prevents 60 minutes of warm mesenteric ischemia/reperfusion injury in rats

Teke, Zafer; Kabay, Burhan; Aytekin, Faruk Onder; Yenisey, Cigdem; Demirkan, Nese Calli; Sacar, Mustafa; Erdem, Ergun; Ozden, Akin

doi:10.1016/j.amjsurg.2006.06.054

« Previous Next »The American Journal of Surgery
Volume 194, Issue 2 , Pages 255-262, August 2007

Pyrrolidine dithiocarbamate prevents 60 minutes of warm mesenteric ischemia/reperfusion injury in rats

Zafer Teke, M.D.
- Faculty of Medicine, Department of General Surgery, Pamukkale University, 20070 Denizli, Turkey
- Corresponding author. Pamukkale University, School of Medicine, Department of General Surgery, 20070 Kinikli, Denizli, Turkey. Tel.: +90 542 2644046; fax: +90 258 2134922.
Burhan Kabay, M.D.
- Faculty of Medicine, Department of General Surgery, Pamukkale University, 20070 Denizli, Turkey
Faruk Onder Aytekin, M.D.
- Faculty of Medicine, Department of General Surgery, Pamukkale University, 20070 Denizli, Turkey
Cigdem Yenisey, Ph.D.
- Faculty of Medicine, Department of Biochemistry, Adnan Menderes University, 09100 Aydin, Turkey
Nese Calli Demirkan, M.D.
- Faculty of Medicine, Department of Pathology, Pamukkale University, 20070 Denizli, Turkey
Mustafa Sacar, M.D.
- Faculty of Medicine, Department of Cardiovascular Surgery, Pamukkale University, 20070 Denizli, Turkey
Ergun Erdem, M.D.
- Faculty of Medicine, Department of General Surgery, Pamukkale University, 20070 Denizli, Turkey
Akin Ozden, M.D.
- Faculty of Medicine, Department of General Surgery, Pamukkale University, 20070 Denizli, Turkey

Received 20 March 2006; received in revised form 16 June 2006

Abstract

Background

Pyrrolidine dithiocarbamate (PDTC) is a low-molecular-weight thiol antioxidant and potent inhibitor of nuclear factor-κB (NF-κB) activation. It has been shown to attenuate harmful effects of ischemia/reperfusion (I/R) injury in many organs. In recent animal studies, destructive effects of reperfusion injury has been demonstrated. In this study, we aimed to investigate whether PDTC prevents harmful effects of superior mesenteric I/R injury in rats.

Methods

Wistar-albino rats were randomly allocated into the following 4 groups: (1) sham-operated group—these animals underwent laparotomy without I/R injury (group I, n = 12); (2) sham+PDTC group—identical to sham-operated rats except for the administration of PDTC (100 mg/kg intravenous bolus) 30 minutes prior to the commencement of the experimental period (group II, n = 12); (3) I/R group—these animals underwent laparotomy and 60 minutes of ischemia followed by 120 minutes of reperfusion (group III, n = 12); (4) PDTC-treated group (100 mg/kg, intravenously, before the I/R, group IV, n = 12). All animals were killed, and intestinal tissue samples were obtained for investigation of intestinal mucosal injury, myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, glutathione (GSH) levels, and intestinal edema.

Results

There was a statistically significant decrease in GSH levels, along with an increase in intestinal mucosal injury scores, MPO activity, MDA levels, and intestinal tissue wet-to-dry weight ratios in group III when compared to groups I, II, and IV (P < .05). However, PDTC treatment led to a statistically significant increase in GSH levels, along with a decrease in intestinal mucosal injury scores, MPO activity, MDA levels, and intestinal tissue wet-to-dry weight ratios in group IV (P < .05).

Conclusions

This study showed that PDTC treatment significantly prevented the reperfusion injury caused by superior mesenteric I/R. Further clinical studies are needed to clarify whether PDTC may be a useful therapeutic agent to use in particular operations where the reperfusion injury occurs.

Keywords: Pyrrolidine dithiocarbamate, Ischemia-reperfusion, Reperfusion injury, Mesenteric ischemia, Myeloperoxidase, Malondialdehyde, Glutathione