Protective effect of pyrrolidine dithiocarbamate on liver injury induced by intestinal ischemia-reperfusion in rats.

ABSTRACT

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). CONCLUSION: 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.