BACKGROUND: The potential of U-74389G in attenuating liver damage after ischemia and reperfusion of the liver was studied in a swine model.MATERIALS AND METHODS: Eighteen pigs, weighting 28-35 kg, were used in the study. The animals were divided into the following three experimental groups: Group A (control group): Ischemia time 30 min and reperfusion for 120 min (with tissue and blood sampling at both 60 min (A-60) and 120 min (A-120)); Group B: Ischemia time 30 min, U-74389G intraportal injection, and reperfusion for 60 min; and Group C: Ischemia time 30 min, U-74389G intraportal injection, and reperfusion for 120 min. The dose of U-74389G administered was 10 mg/kg animal body weight. Anesthesia was induced with propofol, pancuronium, and fentanyl. Surgery was performed through a midline laparotomy. The portal vein and the common hepatic artery were isolated and prepared for occlusion.RESULTS: Histopathological evaluation revealed a statistically significant difference in portal infiltration in the liver tissue between control group A-60 and group B (P = 0.01), and between control group A-120 and group C (P = 0.002). Hemodynamic and metabolic data in the control and therapy groups at 0, 30, 60, and 120 min were not statistically significantly different. Tissue malondialdehyde levels were statistically significantly different. Tumor necrosis factor-alpha values were statistically significantly different between groups A-60 and B but not between groups A-120 and C.CONCLUSION: Based on the histological data and the reduction of the malondialdehyde and tumor necrosis factor-alpha levels, administration of U-74389G in ischemia-reperfusion injury of the liver in a swine model has potential in attenuating liver damage.