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Background: Hepatic ischemia-reperfusion (HIR) is a severe condition that is seen after hepatic arterial injury and in hepatic grafts in living donor transplantation. HIR not only causes liver injury by lipid peroxidation, but also stimulates systemic and portal endotoxemia. Also, lipopolysaccharide (LPS) induces hepatic injury mediated by inducible nitric oxide synthase (iNOS). There is little knowledge on the role of specific iNOS inhibitors in prevention of HIR injury followed by LPS administration. The aim of this study on a LPS induced HIR model was to investigate the effect of aminoguanidine (AG) administration on hepatic tissue iNOS expression and lipid peroxidation when given before or after LPS., Methods: Six groups were designed; A: Sham, B: HIR, C: HIR + AG, D: HIR + LPS, E: HIR + LPS + AG, F: HIR + AG + LPS. No substance was given to the rats in Group A and B. HIR injury was induced with vascular occlusion for 45 min and reperfusion for 45 min. Drugs were given intraperitoneally 10 min before reperfusion. Serum and tissue analysis for myeloperoxidase (MPO), and malondialdehyde (MDA), and tissue NA+/K+ adenosine 5'triphosphatases (ATPase) and tissue iNOS staining were performed. Permission for this study was obtained from the local Ethics Committee., Results: The level of MPO, MDA, and iNOS staining scores in Group B were significantly higher than Group A and ATPase was lower in Group B (P < 0.05). Contrary to results in Group C, results of MPO, MDA, and iNOS staining scores of Group D was higher than Group B (P < 0.05); however, although iNOS in Group C was lower than Group B, the difference was not significant (P > 0.05). MPO and MDA levels of Groups E and F were significantly lower than Group D. Level of ATPase in Group F was significantly different from Groups D and E. iNOS scoring was low in Group F compared with Group D (P < 0.05). MDA, MPO, and iNOS levels of Group F was lower than Group E, and ATPase of Group F was higher than Group E (P < 0.05)., Conclusions: The results of this study in a LPS induced HIR model showed that LPS after HIR aggravated HIR injury by increasing neutrophil activation and lipid peroxidation both in serum and liver tissue and iNOS in liver, and depleting energy in liver. AG, a selective iNOS inhibitor, ameliorated the negative effects of endotoxemia induced by LPS after HIR; however, energy depletion and iNOS expression in liver tissue were attenuated only when AG was administered prior to LPS. The findings of this study supported the hypothesis that LPS after HIR would aggravate HIR injury and AG would ameliorate this aggravated injury.

Background: We aimed to investigate the effect of N-acetylcysteine (NAC) on pulmonary lipid peroxidation and tissue damage in experimental obstructive jaundice (OJ) stimulated by lipopolysaccharide (LPS) in this study., Materials and Methods: We randomized 40 rats into five groups. Group A: Sham (n = 8); group B: OJ (n = 8); group C: OJ + lipopolysaccharide (LPS; n = 8); group D: OJ + NAC + LPS (n = 8); group E: OJ + LPS + NAC (n = 8). OJ was performed by common bile duct ligation and division in all groups except the sham group. At the fifth day, the rats were jaundiced. At the fifth day of OJ, LPS was injected 10 mg/kg intraperitoneally to the rats and at the tenth day, the rats were sacrificed in group C. In group D; at the fifth day of OJ, NAC was started 100 mg/kg subcutaneously and the same dose NAC injection repeated every day for 5 days. At the tenth day of OJ, LPS was injected 10 mg/kg intraperitoneally to the rats and then after 6 h they were sacrificed. In group E; 10 mg/kg LPS was administered intraperitoneally at fifth day of OJ and after then NAC was started 100 mg/kg subcutaneously and the same dose NAC injection repeated every day for 5 days and at the tenth day, the rats were sacrificed. Tissue samples were harvested through a midline incision, and lungs were resected and examined histopathologically and immunohistochemically for tissue damage scoring. The blood was taken by cardiac puncture and malondialdehyde (MDA), myeloperoxidase (MPO), and levels of total antioxidant status were detected with biochemical methods to evaluate lung tissue damage., Results: Increase in lung and serum MDA and MPO levels, as well as decrease in total antioxidant status, were observed in groups B and C when compared with the sham group (P = 0.0001, for each comparison). Furthermore, the lung tissue damage was observed in the same groups by histopathological examination when compared with sham group. There was significant decrease at serum and lung MPO and MDA levels after the NAC application in groups D and E, when compared with group C (P = 0.0001, for each comparison). Antioxidant status in groups D and E were increased in the presence of NAC (P = 0.0001, for each comparison). Lung histology was prevented relatively in group D when compared with groups B and C., Conclusion: Results of the study indicate that NAC has protective effect on pulmonary lipid peroxidation and tissue damage before and after LPS administration.