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

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 e...

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Bibliographic Details
Published in:The American journal of surgery 2007-08, Vol.194 (2), p.255-262
Main Authors: Teke, Zafer, M.D, Kabay, Burhan, M.D, Aytekin, Faruk Onder, M.D, Yenisey, Cigdem, Ph.D, Demirkan, Nese Calli, M.D, Sacar, Mustafa, M.D, Erdem, Ergun, M.D, Ozden, Akin, M.D
Format: Article
Language:English
Subjects:
Abdomen
Animals
Antioxidants - therapeutic use
Biological and medical sciences
Gene expression
General aspects
Glutathione
Glutathione - metabolism
Intestine, Small - blood supply
Intestine, Small - metabolism
Intestine, Small - pathology
Ischemia
Ischemia-reperfusion
Laboratory animals
Leukocytes
Male
Malondialdehyde
Malondialdehyde - metabolism
Medical sciences
Mesenteric ischemia
Methods
Myeloperoxidase
Permeability
Peroxidase - metabolism
Prevention and actions
Public health. Hygiene
Public health. Hygiene-occupational medicine
Pyrrolidine dithiocarbamate
Pyrrolidines - therapeutic use
Rats
Rats, Wistar
Reperfusion injury
Reperfusion Injury - metabolism
Reperfusion Injury - pathology
Reperfusion Injury - prevention & control
Rodents
Studies
Surgery
Thiocarbamates - therapeutic use
Warm Ischemia
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Summary: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.
ISSN:0002-9610
1879-1883
DOI:10.1016/j.amjsurg.2006.06.054