S-nitroso-N-acetylcysteine ameliorates ischemia-reperfusion injury in the steatotic liver.

BACKGROUND: Steatosis is currently the most common chronic liver disease and it can aggravate ischemia-reperfusion (IR) lesions. We hypothesized that S-nitroso-N-acetylcysteine (SNAC), an NO donor component, can ameliorate cell damage from IR injury. In this paper, we report the effect of SNAC on liver IR in rats with normal livers compared to those with steatotic livers. METHODS: Thirty-four rats were divided into five groups: I (n=8), IR in normal liver; II (n=8), IR in normal liver with SNAC; III (n=9), IR in steatotic liver; IV (n=9), IR in steatotic liver with SNAC; and V (n=10), SHAN. Liver steatosis was achieved by administration of a protein-free diet. A SNAC solution was infused intraperitoneally for one hour, beginning 30 min. after partial (70%) liver ischemia. The volume of solution infused was 1 ml/100 g body weight. The animals were sacrificed four hours after reperfusion, and the liver and lung were removed for analysis. We assessed hepatic histology, mitochondrial respiration, oxidative stress (MDA), and pulmonary myeloperoxidase. RESULTS: All groups showed significant alterations compared with the group that received SHAN. The results from the steatotic SNAC group revealed a significant improvement in liver mitochondrial respiration and oxidative stress compared to the steatotic group without SNAC. No difference in myeloperoxidase was observed. Histological analysis revealed no difference between the non-steatotic groups. However, the SNAC groups showed less intraparenchymal hemorrhage than groups without SNAC (p=0.02). CONCLUSION: This study suggests that SNAC effectively protects against IR injury in the steatotic liver but not in the normal liver.

Timing-dependent protection of hypertonic saline solution administration in experimental liver ischemia/reperfusion injury.

BACKGROUND: During liver ischemia, the decrease in mitochondrial energy causes cellular damage that is aggravated after reperfusion. This injury can trigger a systemic inflammatory syndrome, also producing remote organ damage. Several substances have been employed to decrease this inflammatory response during liver transplantation, liver resections, and hypovolemic shock. The aim of this study was to evaluate the effects of hypertonic saline solution and the best timing of administration to prevent organ injury during experimental liver ischemia/reperfusion. METHODS: Rats underwent 1 hr of warm liver ischemia followed by reperfusion. Eighty-four rats were allocated into 6 groups: sham group, control of ischemia group (C), pre-ischemia treated NaCl 0.9% (ISS) and NaCl 7.5% (HTS) groups, pre-reperfusion ISS, and HTS groups. Blood and tissue samples were collected 4 hr after reperfusion. RESULTS: HTS showed beneficial effects in prevention of liver ischemia/reperfusion injury. HTS groups developed increases in AST and ALT levels that were significantly less than ISS groups; however, the HTS pre-reperfusion group showed levels significantly less than the HTS pre-ischemia group. No differences in IL-6 and IL-10 levels were observed. A significant decrease in mitochondrial dysfunction as well as hepatic edema was observed in the HTS pre-reperfusion group. Pulmonary vascular permeability was significantly less in the pre-reperfusion HTS group compared to the ISS group. No differences in myeloperoxidase activity were observed. The liver histologic score was significantly less in the pre-reperfusion HTS group compared to the pre-ischemia HTS group. CONCLUSION: HTS ameliorated local and systemic injuries in experimental liver ischemia/reperfusion. Infusion of HTS in the pre-reperfusion period may be an important adjunct to accomplish the best results.

S-nitroso-N-acetylcysteine ameliorates ischemia-reperfusion injury in the steatotic liver

BACKGROUND: Steatosis is currently the most common chronic liver disease and it can aggravate ischemia-reperfusion (IR) lesions. We hypothesized that S-nitroso-N-acetylcysteine (SNAC), an NO donor component, can ameliorate cell damage from IR injury. In this paper, we report the effect of SNAC on liver IR in rats with normal livers compared to those with steatotic livers. METHODS: Thirty-four rats were divided into five groups: I (n=8), IR in normal liver; II (n=8), IR in normal liver with SNAC; III (n=9), IR in steatotic liver; IV (n=9), IR in steatotic liver with SNAC; and V (n=10), SHAN. Liver steatosis was achieved by administration of a protein-free diet. A SNAC solution was infused intraperitoneally for one hour, beginning 30 min. after partial (70 percent) liver ischemia. The volume of solution infused was 1 ml/100 g body weight. The animals were sacrificed four hours after reperfusion, and the liver and lung were removed for analysis. We assessed hepatic histology, mitochondrial respiration, oxidative stress (MDA), and pulmonary myeloperoxidase. RESULTS: All groups showed significant alterations compared with the group that received SHAN. The results from the steatotic SNAC group revealed a significant improvement in liver mitochondrial respiration and oxidative stress compared to the steatotic group without SNAC. No difference in myeloperoxidase was observed. Histological analysis revealed no difference between the non-steatotic groups. However, the SNAC groups showed less intraparenchymal hemorrhage than groups without SNAC (p=0.02). CONCLUSION: This study suggests that SNAC effectively protects against IR injury in the steatotic liver but not in the normal liver.

Ischemic preconditioning prevents apoptotic cell death and necrosis in early and intermediate phases of liver ischemia-reperfusion injury in rats.

Ischemic preconditioning (IPC) may be useful in attenuating the hepatic ischemia reperfusion (IR) syndrome by means of improving cell resistance to anoxia and reoxygenation and preventing cell death. Since there are insufficient data available regarding the chronology of preconditioning effects, we investigated the role of IPC, to test the hypothesis that liver protection would occur during the early and intermediate phases of the reperfusion period. Wistar rats (n = 72) were randomly assigned into six experimental groups, 12 animals each. A 40-min ischemia to the left lateral and median liver lobes was induced by selective hepatic pedicle clamping followed by 30 min or 240 min of reperfusion (IR30 and IR240). IPC groups (IPC30 and IPC240) underwent a 10 min of ischemia followed by 10 min of reperfusion preceding the definitive 40-min ischemic period. Sham-operated animals were followed for 30 and 240 min. Hepatic enzymes and histological evaluation were performed after the reperfusion period. Hepatic ischemia-reperfusion (IR30 and IR240) induced marked increases in liver enzymes levels after 30 min and particularly after 240 min. IPC effectively attenuated those enzymatic increases. Microvesicular steatosis was observed after 30 min, but not 240 min, of reperfusion in both IPC and IR livers. Necrosis was detected in 66.7% of IR240 and only in 8.3% of IPC240. Both hepatocyte and sinusoidal apoptosis were markedly attenuated by IPC. We conclude that IPC provided protection against hepatic ischemia reperfusion injury in early and intermediate phases of the reperfusion period, reducing hepatic enzymatic leakage and ameliorating hepatic apoptosis and necrosis.

No evidence of de novo amyloidosis in recipients of domino liver transplantation: 12 to 40 (mean 24) month follow-up.

UNLABELLED: Domino liver transplantation (DLT) has been performed for selected recipients at several centers, but de novo amyloidosis in recipients of livers from patients with familial amyloid polyneuropathy (FAP) remains a serious concern. AIM: To evaluate the occurrence of de novo amyloidosis in recipients of DLT. PATIENTS AND METHODS: Seven recipients of FAP livers were followed for clinical and electroneuromyographic signs of FAP and also for de novo amyloid deposition in the gut. RESULTS: No signs and symptoms of de novo FAP nor any evidence of amyloid deposits in the gut were observed in recipients of DLT after a mean follow-up of 24 [12-40] months. CONCLUSIONS: Signs and symptoms of FAP do not occur early in recipients of DLT. These livers could therefore be offered to patients suitable for conventional LT, particularly older subjects in whom the event of de novo amyloidosis would seem improbable.