Pyrrolidine dithiocarbamate prevents 60 minutes of warm mesenteric ischemia/reperfusion injury 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 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.
Teke
Zafer
Z
Faculty of Medicine, Department of General Surgery, Pamukkale University, 20070 Denizli, Turkey. zteke_md@yahoo.com
Kabay
Burhan
B
Aytekin
Faruk Onder
FO
Yenisey
Cigdem
C
Demirkan
Nese Calli
NC
Sacar
Mustafa
M
Erdem
Ergun
E
Ozden
Akin
A
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D007421:Intestine, Small / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011759:Pyrrolidines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013859:Thiocarbamates / Q000627:therapeutic use*; D052096:Warm Ischemia
D000975:Antioxidants; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D008315:Malondialdehyde; D009195:Peroxidase; D005978:Glutathione