Endotoxaemia In Obstructive Jaundice Research Articles

Preventing oxygen free radical damage by proanthocyanidin in obstructive jaundice.

Tissue damage and endotoxemia in obstructive jaundice are attributed to the increase in oxygen free-radicals. We aimed at evaluating the possible protective effect of grape seed proanthocyanidin extract (GSPE), which is a potent exogenous free-radical scavenger and antioxidant. The study was performed at the Necmettin Erbakan University Meram School of Medicine Research and Application Center for Experimental Medicine Laboratory with ethical approval. 30 Wistar-Albino rats were used and were divided into 3 groups. The common bile duct was identified and only dissected in the first group (sham). Following dissection of the common bile duct it was ligated with 4/0 silk just above the pancreas in the second group (control). After ligation of the common bile duct, 100mg/kg/day GSPE was administered via orogastric lavage for 10 days in the third group. Biochemical values revealed a statistically significant difference between Group I and the others. There was no difference between Group II and III regarding biochemical values. There was a statistically significant difference, however, between Group II and III with regards to nitric oxide levels. There was a statistically significant difference between Group I and the other groups concerning hepatic and pulmonary tissue damage on histopathologic evaluation. There was no difference among the groups with regards to renal tubular damage. Proanthocyanidin is an effective natural antioxidant in decreasing the level of tissue damage caused by oxygen free-radicals.

Effect of Ruigan on liver function of Perioperative Treatment in Obstructive Jaundice

Objective To investigate the effect of Ruigan (L-omithine-L-aspartate) on liver function of perio-perative treatment. Methods 58 patients with obstructive jaundice and having been done operation were randomly di-vided into two groups:ruigan group (cured group,32 cases) and routine hugan group (control group,26 cases). The levels of liver function and endotoxin were detected when being in hospital, before operation and after operation re-spectively. Results Treatment with ruigan could improve the liver function in perioperation, which has significant difference when compared to the control group (P < 0.05).. Ruigan could reduce the level of endotoxin before and af-ter operation (P < 0.05) and improve endotoxaemia in obstructive jaundice. Conclusion Ruigan would improve the liver function and the endotoxaemia in the perioperative obstructive jaundice. Key words: obstructive jaundice,Ruigan(L-omithine-L-aspartate), liver function, endotoxin

The Effect of Aminoguanidine on Blood and Tissue Lipid Peroxidation in Jaundiced Rats With Endotoxemia Induced With LPS

Obstructive jaundice (OJ) is a severe condition that leads to several complications. One of the important problems in OJ is the increased incidence of endotoxemia, which is the result of bacterial translocation (BT) and defective host immune response. Lipid peroxidation (LP) is an important problem in OJ and sepsis in which nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity are increased and antioxidative activity is decreased. Formation of peroxynitrite (ONOO−) anion leads to cellular damage and apoptosis. In this experimental study, we explore the effect of specific iNOS inhibitor aminoguanidine (AG) on blood and tissue (liver and renal) LP and iNOS levels in jaundiced rats with endotoxemia induced with lipopolysaccharide (LPS). Rats were randomized into six groups; group A, sham; group B, obstructive jaundice (OJ); group C, OJ + LPS; group D, OJ + AG; group E, OJ + LPS + AG; group F, OJ + AG + LPS. Serum malondialdehyde (MDA) and serum myeloperoxidase (MPO) activity and liver and renal tissue MDA, MPO, and Na+/K+-ATPase activity levels were detected in biochemical methods. Liver and renal tissue iNOS levels were examined immunohistopathologically. Serum and tissue MDA and MPO levels and tissue iNOS expression were increased significantly in groups B, C, and E, while tissue ATPase levels were decreased significantly in the same groups. In the group treated with AG (group D), serum and tissue MDA and MPO levels and tissue iNOS expression were decreased while tissue ATPase levels were increased significantly. In group F, if AG was administrated before LPS, we observed that serum and tissue MDA and MPO levels and tissue iNOS expression were decreased while tissue ATPase levels were increased significantly. Thus, our study showed that AG had a protective effect when it was administrated before LPS, but it failed to prevent tissue iNOS expression and LP if there was established endotoxemia in OJ.

Effect of N-Acetylcysteine on Blood and Tissue Lipid Peroxidation in Lipopolysaccharide-Induced Obstructive Jaundice

In obstructive jaundice, free radical production is increased and antioxidative activity is reduced. N-Acetylcysteine (NAC) has a beneficial effect with anti-inflammatory and antioxidant activity, acting as a free radical scavenger. NAC inhibits inducible nitric oxide synthase, suppresses cytokine expression/release, and inhibits adhesion molecule expression and nuclear factor kappa B. The aim of this study was to investigate the effects of NAC on liver/renal tissue and serum lipid peroxidation in lipopolysaccharide (LPS)-induced obstructive jaundice. We randomized 60 rats into 6 groups: group 1, Sham; group 2, obstructive jaundice (OJ) induced after bile-duct ligation; group 3, OJ + NAC (100 mg kg− 1 subcutaneously); group 4, OJ + LPS (10 mg kg-1); group 5, OJ + NAC + LPS; and group 6, OJ + LPS + NAC. For each group, the biochemical markers of lipid peroxidation and the antioxidant products were measured in serum and liver/renal tissue after sacrifice. Almost all lipid peroxidation products levels were increased and antioxidant products levels were decreased in groups who received LPS (groups 4, 5, and 6), but the effect was less remarkable when NAC was administered before LPS (group 5). The same trend was seen for groups with OJ ± LPS who did not received NAC or received it after induced toxemia (groups 2, 4, and 6) as compared to groups 1 and 3. Moreover, in the case of OJ + LPS, rats treated with NAC before LPS (group 5) had lower lipid peroxidation products levels and higher antioxidant products levels as compared to those who did not received NAC (group 4). This phenomenon was not reproducible with NAC administered after LPS (group 6). Thus, results of this study showed that NAC prevents the deleterious effects of LPS in obstructive jaundice by reducing lipid peroxidation in serum and liver/renal tissue if administered before LPS. Nonetheless, NAC failed to prevent the lipid peroxidation in the case of established endotoxemia in obstructive jaundice.

The effect of N-acetylcysteine (NAC) on liver and renal tissue inducible nitric oxide synthase (iNOS) and tissue lipid peroxidation in obstructive jaundice stimulated by lipopolysaccharide (LPS)

Morbidity and mortality rates are very high in obstructive jaundice when it is associated with sepsis and multiple organ failure. Nitric oxide (NO) formation and increased expression of inducible nitric oxide synthase (iNOS) also take place in obstructive jaundice (OJ). N-Acetylcysteine (NAC) has a beneficial effect by demonstrating anti-inflammatory activity such as inhibits cytokine expression/release, inhibiting the adhesion molecule expression and inhibiting nuclear factor kappa B (NFκB). The aim of this study was to investigate the effects of NAC on liver and renal tissue iNOS, and liver tissue lipid peroxidation in lipopolysaccharide (LPS) induced obstructive jaundice. We randomized 48 rats into six groups. Group A: Sham group; group B: OJ group; group C: OJ+NAC; group D: OJ+LPS ( Escherichia coli LPS serotype L-2630, 100 mg, Sigma) group E: OJ+NAC+LPS; group F: OJ+LPS+NAC. NAC was started subcutaneously 100 mg/kg. LPS was injected intraperitoneally and then at the tenth day we sacrificed the rats. Liver malondialdehyde (MDA) increased and liver ATPase decreased in groups B–D when compared to group A. After the administration of NAC (groups C–E), liver MDA levels decreased, tissue ATPase levels increased as compared to other groups. The liver and renal tissue iNOS expression was increased in groups B, D, and F. After the administration of NAC (groups C–E) the liver and renal tissue iNOS expression were decreased. Our results indicated that NAC prevented the deleterious effects of LPS in OJ by reducing iNOS expression via lipid peroxidation in liver and renal tissue; if it was administrated before LPS. But NAC failed to prevent the iNOS expression and lipid peroxidation if there was established endotoxemia in OJ.

The effect of PARS inhibition on ileal histopathology, apoptosis and lipid peroxidation in LPS-induced obstructive jaundice

In our experimental study, we investigated the protective effect of 3-aminobenzamide (3-AB), the poly (ADP-ribose) synthetase (PARS inhibitor), on the ileal histopathology and the apoptosis in lipopolysaccharide (LPS)-induced inflammation in rats with obstructive jaundice (OJ). We randomized 40 rats into five groups. Group 1: sham group; Group 2: OJ group; Group 3: OJ+LPS; Group 4: OJ+3-AB+LPS; Group 5: OJ+LPS+3-AB. At the fifth day; the rats were jaundiced. In Group 3; 10 mg kg −1 LPS was injected intraperitoneally at the fifth day and then after 6 h the rats were sacrificed. In Group 4; 10 mg kg −1 3-AB was administrated intraperitoneally at the fifth day and repeated daily for 3 days and at the eighth day, 10 mg kg −1 LPS was injected intraperitoneally. In Group 5, 10 mg kg −1 LPS was injected intraperitoneally at the fifth day and after 6 h 10 mg kg −1 3-AB was administrated intraperitoneally and repeated daily for 3 days. At the eighth day, rats were sacrificed. Blood samples were taken for detection of serum MDA levels. Ileum samples were taken after relaparotomy for histopathological examination to evaluate the endotoxin-related intestinal injury and Caspase-3 apoptosis and for detection of tissue MDA and ATPase activities. There was marked destruction of villous and crypt epithelial cells and extensive apoptosis in Groups 3 and 5 in histopathological examination. In Group 4, the scores of intestinal mucosal damage and apoptotic cells were reduced significantly ( P<0.05). On the other hand, the scores of intestinal mucosal damage and apoptotic cells were not improved in Group 5. After the administration of 3-AB (Group 4), serum and ileal MDA levels decreased, ileal ATPase increased as compared to Groups 1 and 2. Our study showed that 3-AB prevented the mucosal damage and apoptotic loss of intestinal epithelial cells significantly if it was administrated before LPS. However, 3-AB failed to prevent the mucosal damage and apoptotic loss of intestinal epithelial cells significantly if there was established endotoxemia in OJ.

Kupffer cell depletion does not significantly reduce the hepatic proinflammatory cytokine response to portal endotoxaemia in obstructive jaundice

The data suggest that, although Kupffer cells appear to initiate the inflammatory response to endotoxin in obstructive jaundice, other hepatic cells release proinflammatory cytokines subsequently.

The hepatic response to portal endotoxaemia in obstructive jaundice down-regulates neutrophil respiratory burst activity

Both pro- and anti-inflammatory cytokines are elevated in this model of obstructive jaundice. The global effect of the increased inflammatory response is a down-regulation of neutrophil respiratory burst activity. This may result in subsequent immunological dysfunction and anergy, as a result of a prominent anti-inflammatory response, increasing the susceptibility to septic complications. The use of the neutrophil chemiluminescence assay may be a more reliable assessment of the effects of the inflammatory balance in obstructive jaundice rather than measurement of individual cytokines.

Role of the gut in the pathophysiology of extrahepatic biliary obstruction.

Gram negative septic events are the commonest source of morbidity and mortality as a result of surgery in jaundiced patients. The large intestine provides the major source of Gram negative bacteria in mammals and is implicated in the pathogenesis of systemic endotoxaemia in obstructive jaundice. Bile salts have an important part in maintaining indigenous microecological homeostasis through their emulsifying properties. The aim was to investigate the effects of biliary obstruction and isolated external biliary diversion on gastro-intestinal structure and caecal bacterial flora in relation to bacterial translocation. Six groups of adult male Wistar rats were studied (no operation, sham operated, and bile duct ligated (BDL) for one and three weeks and a choledocho-vesical fistula (CDVF) for one week). At the end of the study period plasma was assayed for evidence of endotoxaemia and the animals were tested for bacterial translocation to the mesenteric lymph node complex (MLNC), liver, lungs, and spleen. Quantitative and qualitative bacteriological studies were performed on the caecal contents and segments of colon and terminal ileum were washed and prepared for histological assessment. Bacterial translocation was significantly increased in the BDL1 (68.8%) and BDL3 (60%) groups compared with the sham1 (6.3%), sham3 (9.1%), No operation (0%), and CDVF1 (16.7%) groups. Although translocation was more pronounced in the BDL1 group, this was almost exclusively to the MLNC compared with the more widespread translocation to other organs in the BDL3 group. The BDL3 group was the only group with significantly raised concentrations of endotoxin and anticore glycolipid. The caecal Gram negative aerobic counts were significantly increased in the BDL1 and CDVF1 groups compared with all other groups. There was evidence of structural abnormalities in the terminal ileum of rats jaundiced for three weeks, but not in the other groups. Biliary obstruction for one and three weeks promotes bacterial translocation although the mechanisms may be different. Absence of intralumenal bile results in a significant but self limiting increase in the Gram negative aerobic population, which may account for translocation in the early stages of biliary obstruction. As the duration of biliary obstruction increases systemic endotoxaemia is a consistent feature which, combined with factors such as immunological depression and physical disruption of gut barrier function, may promote bacterial translocation perpetuating systemic sepsis.

Bacterial Translocation and Endotoxemia in Obstructive Jaundice: The Protective Effect of Lactulose

This is an experimental study in rats, examining bacterial translocation and endotoxemia in obstructive jaundice, as well as the protective effect of lactulose, an endotoxin-binding agent. Four groups were used: I = control, II = sham, III = common bile duct ligation and IV = common bile duct ligation + lactulose. Aerobic cultures of mesenteric lymph nodes and liver were performed, and endotoxin was measured in the portal vein and aorta. The aerobic bacterial concentration in the cecum was determined and the terminal ileum was examined histologically. The study showed that there was increased bacterial translocation as well as systemic and portal endotoxemia in all jaundiced animals. Lactulose treatment does not influence the occurrence of bacterial translocation, but it significantly reduced endotoxemia. All jaundiced animals presented an insignificant increase in their aerobic cecal flora, independently of lactulose treatment. Histology showed significant changes in intestinal morphology, which may contribute to disruption of the intestinal mucosal barrier. Our results indicate that lactulose treatment (a) had no effect on bacterial translocation in jaundiced rats and (b) it may decrease endotoxemia, probably due to intraluminal binding of endotoxin. These findings may be of clinical significance for surgery in the presence of obstructive jaundice.

Endotoxaemia in Obstructive Jaundice

Endotoxaemia in Obstructive Jaundice

Thromboxane as a possible hepatotoxic factor increased by endotoxemia in obstructive jaundice

In a study using rats, we investigated whether liver damage induced by endotoxemia in obstructive jaundice is associated with thromboxane (TX) in order to acertain whether its vasoconstrictive and platelet aggregating properties play a role in reducing liver blood flow. The rats were divided into the following 5 groups; a control group, an endotoxin (Et) group, a bile duct ligation (BDL) group, a bile duct ligation and endotoxin (BDL + Et) group and an OKY046 (Thromboxane synthetase inhibitor) treated bile duct ligation + endotoxin (OKY-BDL + Et) group. The blood TXB2 levels in the Et, BDL and BDL + Et groups were higher than those in the control group. The liver TXB2 levels in the Et and BDL + Et groups were also higher than those in the control group. Liver phospholipids and liver blood flow decreased in the BDL + Et group, whereas in the OKY-BDL + Et group they returned close to the control group levels by decreasing the TXB2 levels in both the liver and blood to normal. These results suggest that the high level of TX in the blood and liver tissue may further aggrevate the liver during endotoxemia in obstructive jaundice by inhibiting liver blood flow.

Endotoxemia in obstructive jaundice: Observations on cause and clinical significance

Perioperative endotoxemia was detected in 24 of 40 patients who underwent operation for obstructive jaundice (bilirubin level greater than 5.8 mg/dl). Endotoxemia was associated with an increased admission serum bilirubin level (p less than 0.05) and white blood cell count (p less than 0.05) and a decreased hematocrit value (p less than 0.05), but there was no significant association with other established preoperative risk factors. Patients with preoperative endotoxemia had a decreased immunoglobulin M anti-J5 endotoxin titer (p less than 0.05) and a decreased serum bile acid concentration (p less than 0.05). Preoperative endotoxemia was associated with reduced creatinine clearance before and after operation (p less than 0.05). There was no association between endotoxemia and clinical sepsis, gram-negative infection, or small-bowel colonization. Patients who died had increased preoperative serum fibrin degradation products (p less than 0.05).