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.     

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.     

Development and reversal of endotoxemia and endotoxin-related death in obstructive jaundice

Gut-derived endotoxemia has been implicated in postoperative complications in patients with jaundice. It is thought that absence of bile in the gut predisposes to portal absorption of endotoxin and endotoxemia is reversed by oral bile salt replacement or internal biliary drainage and return of bile to the gut, but not by external drainage. We believe that the importance of gastrointestinal bile flow has been overestimated and biliary obstruction and the integrity of hepatocyte and Kupffer cell function are more important in the development and reversal of endotoxemia. In experiment 1, serum endotoxin concentrations were measured in control rats (n = 10) after choledochovesical fistula (n = 15) and bile duct ligation (n = 15) and after relief of biliary obstruction by internal drainage (choledochoduodenostomy; n = 8) and sterile external drainage (choledochovesical fistula; n = 8), with a quantitative limulus assay. In experiment 2, mortality rates were measured in similar groups 48 hours after administration of oral endotoxin (5 mg/100 gm) and intravenous lead acetate (5 mg/100 gm). Bilirubin levels were elevated in bile duct ligation (192 +/- 13 mumols/L) compared with control animals and those with choledochovesical fistula, internal drainage, and external drainage (10.6 +/- 1.5 mumols/L). In experiment 1, significant portal endotoxemia and systemic endotoxemia occurred in bile duct ligation (portal, 130.4 +/- 12.9 pg/ml; systemic, 91.8 +/- 11.0 pg/ml) but not in choledochovesical fistula (portal, 49.3 +/- 17.1 pg/ml; systemic, 27.2 +/- 11.5 pg/ml). Relief of obstruction by both internal and external drainage reversed endotoxemia. In experiment 2, significant death occurred in bile duct ligation (13 of 15) but not in choledochovesical fistula (3 of 15), and relief of obstruction by both internal and external drainage prevented death. These results confirm that biliary obstruction is a more important factor than is gastrointestinal bile flow in the development and reversal of endotoxemia.     

去氢胆酸钠治疗阻塞性黄疸内毒素血症的实验研究

目的:观察去氢胆酸钠降低阻塞性黄疸时血清内毒素的效果。方法:将CD大鼠随机分成对照组、胆总管结扎组和胆总管结扎-胆盐治疗组,测定各组血清胆红素、免疫球蛋白IgG、IgM和内毒素。结果:胆总管结扎-胆盐治疗组血清内毒素明显下降（P<0．01）,血清免疫球蛋白IgG、IgM有较明显升高。结论:口服去氢胆酸钠可能有助于降低阻塞性黄疸的血清内毒素。     

Study on mechanism of onset of endogenous endotoxemia during obstructive jaundice--with special reference to involvement of biliary infection

To clarify how biliary infections affect onset of endogenous endotoxemia during obstructive jaundice, I tried to review the clinical result of 104 cases of obstructive jaundice, and conducted a Limulus test of portal and peripheral blood in 20 cases of obstructive jaundice and an animal study using 38 rabbits. In cases of obstructive jaundice complicated by biliary infections, clinical improvement of jaundice became significantly unfavorable, and the outcome of surgical operation was significantly inferior to the cases without biliary infections. The endotoxin positive rate in the portal blood of obstructive jaundice was 65% (13 of 20 cases), among which 10 cases (79.6%) was also positive in the peripheral blood. Of these 10 cases, 7 cases manifested endogenous endotoxemia with no infectious focus, and prognosis of these cases was poor. The endotoxin positive rate in portal blood of obstructive jaundice group was also significantly higher than that of non-jaundice group in animal study, and when the reticuloendothelial system was blocked, the endotoxin positive rate in the peripheral blood showed an increasing tendency. In the animal group with experimental cholangitis, all the endotoxin positive animals in the portal blood were also positive in the peripheral blood. This result suggests that biliary infections accelerate a decrease in the reticuloendothelial function during obstructive jaundice. From these results, endogenous endotoxemia seems to affect the onset of various complications during obstructive jaundice and unfavorable prognosis.     

Protective effect of the intravenous administration of ursodeoxycholic acid against endotoxemia in rats with obstructive jaundice

This study was undertaken to elucidate the effect of the intravenous administration of ursodeoxycholic acid (UDCA) on endotoxemia in rats with obstructive jaundice from the viewpoint of the biliary excretion of lipopolysaccharide (LPS) through hepatocytes. In rats with obstructive jaundice, fluorescein isothiocyanate-labeled LPS was administered via the portal vein and then its biliary excretion was examined. A significant increase in the LPS excretion was thus noticed in UDCA-treated rats at a dose of 0.1μmol/100g body wt. per min. In place of UDCA, sodium taurocholate at the same dose also enhanced the biliary excretion of LPS. Secondly, we also examined whether or not UDCA protects against endotoxemia. In this experiment, nonlabeled LPS was administered via the portal vein and its peripheral concentration was then measured. In UDCA-treated rats, the endotoxin concentration was significantly lower. Finally, to elucidate the effect of UDCA on Kupffer cells, serum tumor necrosis factor (TNF-α) was measured. But UDCA had no effect on the TNF-α level. These findings thus demonstrate that the intravenous administration of UDCA protects against endotoxemia by enhancing the transport of LPS across the hepatocytes from blood to bile without affecting Kupffer cells, and that this biliary excretion of LPS is dependent on bile acids.     

Endotoxemia,disturbance of coagulation,and obstructive jaundice

A prospective study of coagulation disturbances and endotoxemia in 42 patients having major pancreatic or biliary surgery was performed. Endotoxin, soluble fibrin, and fibrin degradation products were measured before and after operation in 28 patients with obstructive jaundice and in 14 nonjaundiced controls. In the control group there was one death and no unexplained fever or postoperative hemorrhage. The jaundiced group had more complications: seven deaths, nine episodes of fever, and six episodes of hemorrhage. Soluble fibrin was detected only in patients with obstructive jaundice, in whom it occurred in 38 percent before operation. Positive endotoxin assay was as common in control patients as in the jaundiced group, but in the latter endotoxin was associated (p < 0.05) with increased FDP and soluble fibrin. Patients with endotoxin or increased FDP levels before operation for jaundice carry a poor prognosis (7 of 11 died). Preoperative bowel preparation in 16 of the jaundiced patients did not affect the outcome.     

Circulating immune complex, endotoxin, and biliary infection in patients with biliary obstruction

Immunoglobulin A-containing circulating immune complexes, immunoglobulin G-containing circulating immune complexes, and endotoxin were measured in the sera of patients with obstructive jaundice. The bile of patients with percutaneous transhepatic biliary drainage was also cultured for bacteriologic studies. There was a significantly positive correlation between the endotoxin levels and both immunoglobulin A-containing circulating immune complex and immunoglobulin G-containing circulating immune complex. The endotoxin levels of the patients with gram-negative infections were significantly increased compared with those of the patients with sterile cultures. The immunoglobulin G-containing circulating immune complex levels of the patients with bacteria in bile were significantly increased compared with those of the patients with sterile cultures. The immunoglobulin A-containing circulating immune complex levels of the patients with bacteria in bile were slightly increased, but the difference did not reach statistical significance. These results indicate that one of the causes of increased circulating immune complex levels may be endotoxemia in combination with biliary infection in patients with biliary obstruction.     

一氧化氮、内皮素在胆道梗阻病程中的变化及意义

目的 了解NO、ET1等在胆石性胆道梗阻病程演进过程中的作用及其临床意义。方法 对胆石性胆道梗阻患者,按黄疸发生时间、血内毒素检测结查、有无急性胆管炎分组比较NO、ET内毒素和肝功能变化关系。结果 梗阻性黄疸I、Ⅱ组NO与ET1呈负相关;Ⅲ组NO与ET1呈负相关。内毒素阳性组、有胆管炎组：NO ET1无相关关系。结论 ①胆道感染、内毒素等导致NO与ET1的协调关系紊乱、NO的正常保护机制受损,这在胆道梗阻所致肝功能衰竭、肝纤维化等发病机制中可能起了重要作用。②检测比较NO／ET的变化关系,可能作为了解肝细胞损害程度、肝储备功能的参考指标。     

Experimental study on the development of endotoxemia in biliary tract infection with special reference to lymphatic pathway at controlled biliary duct pressure

A study was made on the pathway of the endotoxin from the biliary tract into the circulation, using adult mongrel dogs divided into 10 groups primarily with or without thoracic duct drainage. The biliary duct pressure level of 25, 35, and 55 cm saline was maintained by infusing physiological saline into the bile duct. Each level was maintained for a 10-minute period following the intrabiliary infusion of endotoxin 10 mcg/kg. The endotoxin level in arterial and portal blood and in thoracic lymph increased with increment of biliary duct pressure. The endotoxin level in the thoracic lymph was more than 10 times higher than that in blood. At 35 and 55 cm saline of biliary duct pressure, the groups with or without thoracic lymph drainage did not show any significant difference in blood endotoxin level, or moreover, endotoxin shock developed in each group. These findings imply that at high biliary pressure such as 35 or 55 cm saline, endotoxin in the bile duct directly appears in the sinusoid. At low biliary pressure such as 25 cm saline, endotoxin was detected only in thoracic lymph and endotoxemia did not develop.     

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).     

胆汁转流性外引流术对恶性梗阻性黄疸血内毒素水平的影响

目的 :探讨外引流术体外转流胆汁对恶性梗阻性黄疸病人血内毒素水平的影响。方法 :对 14例肿瘤手术不能切除的恶性梗阻性黄疸病人行胆汁转流性外引流术 ,与同期施行的 15例内引流术、2 0例外引流术病人进行手术前后外周血内毒素水平比较。结果 :术前 3组内毒素水平差别无显著性意义 (P>0 .0 5 )。单纯外引流组手术后内毒素水平略高于术前 (P >0 .0 5 ) ;内引流组术后第 2天内毒素水平反而高于术前 (P <0 .0 5 ) ,第 7天、第 14天显著降低 (P <0 .0 5 ,P <0 .0 1) ;体外转流组术后内毒素水平逐渐降低 ,与内引流术组变化基本相同。结论 :胆汁转流性外引流术可降低恶性梗阻性黄疸病人外周血内毒素水平。     

Effect of Oral Glutamine Administration on Bacterial Tanslocation, Endotoxemia, Liver and Ileal Morphology, and Apoptosis in Rats with Obstructive Jaundice

Postoperative complications in patients with obstructive jaundice remain increased when associated with endotoxemia and the inflammatory response due to gut barrier failure. Administration of glutamine has been proposed to maintain the integrity of the gut mucosa and thus reduce bacterial translocation (BT), but the effects of this pretreatment on apoptosis and histologic morphology of various organs affected by BT in obstructive jaundice have not been studied. We therefore studied the effects of oral glutamine supplementation on endotoxemia, BT, liver and terminal ileal morphology, and apoptosis in an experimental model of obstructive jaundice. A total of 60 male Wistar rats were randomly divided into four groups of 15 each: I, controls; II, sham-operated; III, bile duct ligation (BDL); IV, BDL + glutamine (4.5 g/kg/day in drinking water). Ileal samples for histology, DNA and protein content, liver biopsies, mesenteric lymph nodes (MLNs) for culture, and portal and systemic blood samples for endotoxin measurements were obtained 10 days later. Compared to the controls, a significant increase in contaminated MLN and liver samples and increased endotoxemia were noted in group III (p < 0.01) but were significantly reduced in group IV (p < 0.05). Group IV also had a significantly higher number of mitoses per crypt (M/c) (p < 0.05), less apoptotic body counts (ABCs) (p < 0.05), and a higher DNA content than did group III (p < 0.05). Liver biopsies from group III displayed typical changes of large duct obstruction that significantly improved after glutamine treatment, with decreased ductular proliferation. We concluded that supplementation of oral glutamine in the presence of obstructive jaundice ameliorates BT, endotoxemia, and apoptosis and improves the ileal and liver histology.     

Prevention of endotoxaemia in obstructive jaundice--a comparative study of bile salts

Systemic endotoxaemia is associated with postoperative renal dysfunction in obstructive jaundice, and can be prevented by the pre-operative administration of certain bile salts. In order to find the most effective bile salt for use in this condition, a comparison of the anti-endotoxic activities of different bile salts was performed. Bile salts were incubated in vitro with endotoxin and the resultant endotoxin level was measured with a quantitative limulus assay. The in vivo effects of different oral bile salts on the intestinal absorption of radiolabelled endotoxin from rats with obstructive jaundice were compared. The in vitro and in vivo anti-endotoxic activities of bile salts related to their known detergent activities. Deoxycholic acid and its conjugates were the most effective and should be the bile salts of choice for further clinical evaluation in obstructive jaundice in man.     

Gut endotoxin restriction prevents catabolic changes in glutamine metabolism after surgery in the bile duct-ligated rat.

OBJECTIVE: The objective of this study was to investigate the role of gut-derived endotoxemia in postoperative glutamine (GLN) metabolism of bile duct-ligated rats. SUMMARY BACKGROUND DATA: Postoperative complications in patients with obstructive jaundice are associated with gut-derived endotoxemia. In experimental endotoxemia, catabolic changes in GLN metabolism have been reported. Glutamine balance is considered important in preventing postsurgical complications. METHODS: Male Wistar rats were treated orally with the endotoxin binder cholestyramine (n = 24, 150 mg/day) or saline (n = 24). On day 7, groups received a SHAM operation or a bile duct ligation (BDL). On day 21, all rats were subjected to a laparotomy followed 24 hours later by blood flow measurements and blood sampling. Glutamine organ handling was determined for the gut, liver, and one hindlimb. Intracellular GLN muscle concentrations were determined. RESULTS: Compared to the SHAM groups, BDL rats showed lower gut uptake of GLN (28%, p < 0.05); a reversal of liver GLN release to an uptake (p < 0.05); higher GLN release from the hindlimb (p < 0.05); and lower intracellular muscle GLN concentration (32%, p < 0.05). Cholestyramine treatment in BDL rats maintained GLN organ handling and muscle GLN concentrations at SHAM levels. CONCLUSIONS: Disturbances in postoperative GLN metabolism in BDL rats can be prevented by gut endotoxin restriction. Gut-derived endotoxemia after surgery in obstructive jaundice dictates GLN metabolism.     

Effect of Bile Acid Replacement on Endotoxin-induced Tumor Necrosis Factor-a Production in Obstructive Jaundice

There is a high incidence of perioperative morbidity and mortality in patients with obstructive jaundice due to sepsis. Tumor necrosis factor-a (TNF-a) is considered a crucial mediator in inducing and processing the inflammatory cascade. We hypothesize that obstructive jaundice leads to an increased endotoxin-induced TNF-a production and that intestinal bile acid replacement can prevent this phenomenon. Sprague-Dawley rats were randomized to three groups of 12 animals each. Group 1 underwent common bile duct ligation (CBDL) with oral intestinal bile acid (deoxycholic acid 5 mg/100 g body weight/3 times daily) replacement (CBDL + bile acid); group 2 underwent common bile duct ligation with the same amount of normal saline replacement orally (CBDL + saline); and group 3 underwent a sham operation (sham control). After 2 days, endotoxin was given to the animals, and after 90 minutes, tissues (liver and lung) and blood were collected for checking the TNF-a levels and biochemical analyses. Comparisons among these three groups were performed and recorded. While serum and tissue (liver and lung) TNF-a levels of group 2 (CBDL + saline) were significantly increased after endotoxin challenge, these elevations were reduced to control levels (sham control) following oral replacement of intestinal bile acid (CBDL + bile acid). Obstructive jaundice leads to an increased endotoxin-induced TNF-a production and intestinal bile acid replacement can inhibit this phenomenon.     

The nitric oxide donor molsidomine improves survival and reduces hepatocyte apoptosis in cholestasis and endotoxemia

BACKGROUND: Cholestasis and endotoxemia have been demonstrated to cause hepatocyte apoptosis through caspase-mediated pathways. In vitro nitric oxide (NO) donors reduce hepatocyte apoptosis and caspase activation in several models. The nitric oxide donor molsidomine improves survival in an in vivo model of endotoxemia. We tested the effect of molsidomine on survival and hepatocyte apoptosis in a model of obstructive jaundice and endotoxemia. STUDY DESIGN: Sprague-Dawley rats underwent common bile duct ligation on day 1. On day 3, animals were given either 100 mg/kg of molsidomine or an equivalent volume of saline, and 30 minutes later they were given endotoxin 3 mg/kg or 10 mg/kg intravenously. Animals were sacrificed 4 or 16 hours after endotoxin injection. Serum samples were analyzed for alanine aminotransferase and frozen liver samples were analyzed for caspase 3 activity. Paraffin-embedded liver sections were assayed for apoptosis using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay. Survival was measured in a separate experiment in which animals underwent the same protocol, but were given three different doses of endotoxin and were observed for 72 hours before sacrifice. RESULTS: At endotoxin 3 mg/kg, the 72-hour survival in saline-treated animals was 92%, which decreased to 45% at 10 mg/kg and to 29% at 15 mg/kg. All of the molsidomine-treated animals survived all endotoxin doses. Alanine aminotransferase was reduced in molsidomine-treated animals compared with those treated with saline. Apoptosis was attenuated in molsidomine-treated animals. Caspase 3 activity was decreased in molsidomine-treated animals compared with those given saline. CONCLUSIONS: Molsidomine attenuates caspase activation and hepatocyte apoptosis and improves survival after cholestatic endotoxic injury.     

Translocation. Incidental phenomenon or true pathology?

OBJECTIVE: This study was conducted to determine if reduction of early postburn endotoxemia influences the cytokine cascade, clinical manifestations of sepsis, and mortality rate. SUMMARY BACKGROUND DATA: Translocational endotoxemia has been demonstrated postburn in animals and humans. Endotoxin is known to induce the cytokine cascade, which leads to the clinical manifestations of sepsis. Whether reduction of postburn endotoxemia could influence the induction of cytokines has not been demonstrated. METHODS: In a prospective, randomized study, 76 burn patients were given polymyxin intravenously or served as control subjects. Polymyxin B was given intravenously for 1 week postburn in doses designed to neutralize circulating endotoxemia. RESULTS: In the polymyxin group, there was a statistically significant reduction in the plasma endotoxin concentration. There was, however, no reduction in the sepsis score or the interleukin-6 levels, and no differences in mortality rates were seen between the two groups. CONCLUSIONS: Early postburn translocational endotoxemia can be treated with anti-endotoxin agents such as polymyxin B. This, however, does not influence the cytokine cascade or the mortality rate. The systemic inflammatory response syndrome is caused by cytokine induction from the injury and is unaffected by a reduction in the plasma endotoxin concentration.     

Redistribution of intraorgan blood flow in acute, hyperdynamic porcine endotoxemia

In a standardized porcine model of acute, hyperdynamic endotoxemia the distribution of intraorgan blood flow within heart, kidney and brain was analyzed. Twelve pigs received either short-term (23 min) or long-term (205 min) continuous intravenous infusion of endotoxin (Salmonella abortus equi). A high cardiac output/low peripheral resistance state was maintained throughout the 3.5 h observation period. Total organ blood flow in heart, kidney and brain remained high; however, already small amounts of endotoxin provoked a significant redistribution of intraorgan blood flow within the left ventricle and the kidney. These characteristic alterations were absent in a control group of 5 animals subjected to the same protocol, but receiving 0.9% saline instead of endotoxin. Deterioration of respiratory function developed exclusively after continuous intravenous endotoxin infusion over 205 min, indicating incipient organ failure. Using electron microscopy, endothelial cells swelling and entrapment of blood cells in capillaries of the midmyocardium as well as severe ultrastructural damage in the kidney could be demonstrated already after 90 min of endotoxemia in two additional animals. It is concluded that already in the initial phase of acute endotoxemia, in the presence of high cardiac output and high global organ blood flow microcirculatory deterioration and organ failure develops. As small amounts of endotoxin are capable of inducing these alterations, earliest possible diagnosis of endotoxemia should be achieved in critically ill patients.     

Bombesin and neurotensin reduce endotoxemia, intestinal oxidative stress, and apoptosis in experimental obstructive jaundice

OBJECTIVE: To evaluate the effect of bombesin (BBS) and neurotensin (NT) on intestinal histopathology, intestinal oxidative stress, and endotoxemia in experimental obstructive jaundice. SUMMARY BACKGROUND DATA: Obstructive jaundice compromises gut barrier function, resulting in endotoxemia. BBS and NT, exerting various biologic actions on gastrointestinal tissues, preserve gut mucosal integrity in cases of injury or atrophy. METHODS: Seventy male Wistar rats were randomly divided into 5 groups: I = controls, II = sham operated, III = bile duct ligation (BDL), IV = BDL + BBS (30 microg/kg/d), V = BDL + NT (300 microg/kg/d). By the end of the experiment, on day 10, endotoxin was measured in portal and aortic blood. Tissue sections of the terminal ileum were examined histologically, and villus density, mucosal thickness, mitotic activity and apoptosis in crypts were assessed. In addition, ileal mucosa was analyzed for DNA and protein content. To estimate intestinal oxidant/antioxidant equilibrium, lipid peroxidation, protein oxidation, and thiol redox state (reduced glutathione [GSH], oxidized glutathione [GSSG], total nonprotein mixed disulfides [NPSSR], protein thiols [PSH], and protein disulfides [PSSP]) were determined on tissue homogenates from the terminal ileum. RESULTS: BBS or NT administration significantly reduced portal and systemic endotoxemia observed in obstructive jaundice. Both factors reversed obstructive jaundice-induced morphologic features of intestinal atrophy, increasing villus density and mucosal thickness. This effect was accompanied by induction of mitoses and reduction of apoptosis in intestinal crypts. Mucosal DNA and protein content were reduced, although not to significant levels, in BDL animals and restored to control levels after BBS or NT treatment. Moreover, BBS or NT administration protected the intestine in jaundiced rats against oxidative stress, as demonstrated by reduction of intestinal lipid peroxidation, increase of the antioxidant GSH, and decrease of the oxidized forms GSSG and NPSSR, while BBS additionally reduced protein oxidation as well. CONCLUSIONS: Administration of BBS or NT in bile duct-ligated rats exerts beneficial effects on intestinal oxidative stress, cell proliferation, apoptosis, and endotoxemia. This observation might be of potential value in patients with extrahepatic cholestasis.