Protective effect of pyrrolidine dithiocarbamate on liver injury induced by intestinal ischemia-reperfusion in rats.
BACKGROUND
The nuclear translocation of transcription factors may be a critical factor in the intracellular pathway involved in ischemia/reperfusion (I/R) injury. The aim of the study was to evaluate the role of nuclear factor-kappa B (NF-kappaB) in the pathogenesis of liver injury induced by intestinal ischemia/reperfusion (IIR) and to investigate the effect of pyrrolidine dithiocarbamate (PDTC) on this liver injury.


METHODS
Male Wistar rats were divided randomly into three experimental groups (8 rats in each): sham operation group (control group); intestinal/reperfusion group (I/R group): animals received 1-hour of intestinal ischemia and 2-hour reperfusion; and PDTC treatment group (PDTC group): animals that received I/R subject to PDTC treatment (100 mg/kg). The histological changes in the liver and intestine were observed, and the serum levels of tumor necrosis factor-alpha (TNF-alpha), alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver superoxide dismutase (SOD), and nitrite/nitrate (NO) were measured. The immunohistochemical expression and Western blot analysis of liver NF-kappaB and intercellular adhesion molecule-1 (ICAM-1) were observed.


RESULTS
IIR induced liver injury characterized by the histological changes of liver edema, hemorrhage, polymorphonuclear neutrophil (PMN) infiltration, and elevated serum levels of AST and ALT. The serum TNF-alpha level was significantly higher than that of the control group (P<0.01) and a high level of liver oxidant product was observed (P<0.01). These changes were parallel to the positive expression of NF-kappaB and ICAM-1. After the administration of PDTC, the histological changes after liver injury were improved; the levels of SOD and NO in the liver were elevated and reduced, respectively (P<0.01). The expressions of ICAM-1 and NF-kappaB in the liver were weakened (P<0.01).


CONCLUSIONS
NF-kappaB plays an important role in the pathogenesis of liver injury induced by IIR. PDTC, an agent known to inhibit the activation of NF-kappaB, can reduce and prevent this injury.
Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China. txfdl@tom.com
Xiao-Feng
XF
Tian
Ji-Hong
JH
Yao
Ying-Hua
YH
Li
Hai-Feng
HF
Gao
Zhen-Zhen
ZZ
Wang
Chun-Ming
CM
Yang
Shu-Sen
SS
Zheng
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007421:Intestine, Small / Q000098:blood supply*; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011759:Pyrrolidines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013859:Thiocarbamates / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; D015415:Biomarkers; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C020972:pyrrolidine dithiocarbamic acid; D009569:Nitric Oxide; D013482:Superoxide Dismutase