Obstructive Jaundice Impairs Reticuloendothelial Function and Promotes Bacterial Translocation in the Rat

doi:10.1006/jsre.1994.1138

Journal of Surgical Research

Volume 57, Issue 2, August 1994, Pages 238-245

https://doi.org/10.1006/jsre.1994.1138 Get rights and content

Abstract

Septic complications and renal insufficiency following biliary tract surgery are frequently seen in patients with obstructive jaundice. The precise mechanisms for understanding the susceptibility of the jaundiced patients to sepsis are, however, not clear. The present study aimed at investigating the influence of biliary obstruction on the reticuloendothelial function and bacterial translocation at various time intervals in the rat. Reticuloendothelial system (RES) function, as evaluated by measuring blood clearance of intravenously injected ¹²⁵I-labeled Escherichia coli, and bacterial translocation were studied 3 days and 1, 2, and 3 weeks following either sham operation or common bile duct ligation (CBDL) and transection in the rat. RES function was significantly impaired and renal uptake of radiolabeled E. coli was significantly higher in jaundiced animals from Day 3 and on after CBDL (P < 0.01) concomitant with elevation of plasma levels of bilirubin and liver enzymes (P < 0.001) compared with their corresponding controls. The incidence of bacterial translocation 3 days and 1 and 2 weeks after biliary obstruction significantly increased (P < 0.05). We conclude that RES phagocytic function is impaired and the incidence of bacterial translocation is increased in jaundiced rats. These findings might contribute to explain the high susceptibility of postoperative septic complications and renal dysfunction in patients with obstructive jaundice.

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Cited by (83)

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2020, Clinics
Citation Excerpt :
In the current work, the BDL+CLP model technique in young rats was feasible and of rapid execution. Regarding mortality, animals subjected to a greater number of procedures, due to the number of interventions and the accumulation of comorbidities, were expected to have a higher mortality rate as seen in previous works (20,21). This seems to correspond with what is observed in clinical practice, wherein individuals with cirrhosis in the surgical context, and concurrent infectious complications tend to present with higher mortality (22).
In cirrhotic children, infection events and sepsis are more frequent and more severe due to immune dysfunction. The objectives of the current study were therefore to develop an experimental model of infection and sepsis in cirrhotic weaning growing rats, by the use of bile duct ligation (BDL) and cecal ligation and puncture (CLP). Additionally, the correlation of the clinico-histopathological data and serial cytokine levels in septic cirrhotic and non-cirrhotic animals was studied.
Young Wistar rats of age 21 days and of weight between 70-90 g were divided into 12 groups according to the surgical procedure performed: sham (sacrificed after 2 or 4 weeks), BDL (sacrificed after 2 or 4 weeks), CLP (2- or 4-week old animals sacrificed after 12 or 24 hours), BDL+CLP (2- or 4-week old animals sacrificed after 12 hours). Histopathological studies and determination of serum levels of cytokines IL-1 beta, IL-10, and TNF-alpha, for studies of systemic infection, were performed. Murine sepsis scores (MSS) based on the clinical aspects just before euthanasia were also included.
A transitory increase in IL-1, IL-10, and TNF-alpha levels was observed, with different patterns according to the groups. Two-hit groups tended to present with higher values of serum cytokines and histopathological scores than their septic non-cirrhotic counterparts. There was a correlation between mortality rate and MSS (p<0.0001).
The model is feasible and may be utilized in studies on liver cirrhosis and infection in growing animals.
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2017, Ultrasound in Medicine and Biology
Bile duct ligation (BDL) can cause cholangitis, which is known to induce impaired Kupffer cell (KC) function and increased oxygen consumption in a mouse model. It is important to monitor changes in KC function and tissue oxygen saturation, both of which are critical factors in the progression of cholangitis. The purpose of this study is to investigate the impaired phagocytic activity of KC and liver oxygen saturation (sO₂) in a mouse cholangitis model using contrast-enhanced ultrasound imaging (CEUS) and photoacoustic imaging (PAI). A mouse cholangitis model was created by ligation of the common bile duct (CBDL, n = 20), and the left intrahepatic bile duct (BDL-L, n = 19), both of which were compared with the non-ligation groups—right lobe measurement group after left intrahepatic bile duct ligation (BDL-R, n = 19) and the control group (n = 14). The echogenicity and sO₂ were measured by CEUS and PAI and the KC fraction was assessed at 1, 2 and 4 wk after ligation. We found a significantly lower echogenicity of the Kupffer phase in the CBDL and BDL-L groups compared with that in the control and BDL-R groups at 2 wk (p < .01). The CBDL and BDL-L groups showed a lower echogenicity than that of the BDL-R group at 4 wk (p < .01). We found a significantly lower sO₂ of the CBDL and BDL-L groups compared with that of the control and BDL-R groups at 4 wk (p < .01). The CBDL and BDL-L groups showed a higher KC fraction than that of the BDL-R and control groups at each time point (p < .01). In conclusion, our study suggests that the Sonazoid CEUS and PAI could be a useful tool for monitoring impaired KC phagocytic activity and the liver hypoxic state.
Infections of the Biliary Tract
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Studies indicate that absence of bile salts and IgA in the intestine leads to a change in the bacterial flora that colonizes the small intestine. Under normal circumstances, colonization of the duodenum and jejunum with coliforms is limited,27,28 but this has been shown to change in studies of bile duct–ligated rats, indicating a shift in the small bowel flora with Escherichia coli predominating.29 In addition to the change in the bacterial flora of the duodenum, intestinal bacteria are more likely to translocate in rodents with ligated bile ducts.30
The Rho-kinase inhibitor Y-27632 inhibits cholestasis-induced platelet interactions in the hepatic microcirculation
2009, Microvascular Research
Bile duct obstruction is associated with hepatic accumulation of leukocytes and liver injury. Emerging data suggest that platelets may play an important role in tissue damage and inflammation. Herein, we characterized the platelet response in cholestatic liver injury and evaluated the role of Rho-kinase signaling. For this purpose, C57BL/6 mice were treated with the Rho-kinase inhibitor Y-27632 (10 mg/kg) and vehicle before undergoing bile duct ligation (BDL) for 12 h. Platelet rolling and adhesion, formation of platelet aggregates as well as microvascular perfusion in the liver were analyzed using intravital fluorescence microscopy. Liver damage was monitored by measuring serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Administration of Y-27632 reduced the BDL-associated increase of ALT and AST by 95% and 89%, respectively. The inhibition of Rho-kinase also reduced cholestasis-induced platelet rolling and adhesion by more than 46% and 73% in postsinusoidal venules and platelet adhesion in sinusoids by 60%. In addition, Y-27632 decreased platelet aggregation in hepatic sinusoids and postsinusoidal venules by 69% and 81%. BDL caused a significant reduction of hepatic microvascular perfusion. Importantly, pretreatment with Y-27632 restored sinusoidal perfusion in cholestatic animals. Our findings demonstrate that Rho-kinase regulates multiple aspects of platelet interaction in the microcirculation of cholestatic animals. Moreover, inhibition of Rho-kinase signaling not only attenuates platelet responses but also maintains microvascular perfusion and protects against hepatocellular injury in cholestasis. Thus, targeting Rho-kinase signaling may be an effective way to protect against platelet-mediated liver injury in obstructive jaundice.
The ultrastructural research of liver in experimental obstructive jaundice and effect of honey
2008, American Journal of Surgery
To examine the effects of honey on oxidative stress and apoptosis in experimental obstructive jaundice model.
Thirty rats were divided into 3 groups: group I, sham-operated; group II, ligation and division of the common bile duct (BDL); group III, BDL followed by oral supplementation of honey 10 g/kg/d. Liver samples were examined under light microscope and transmission electron microscope. Hepatocyte apoptosis was quantitated using the terminal deoxy-nucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Plasma and blood malondialdehyde (MDA) and glutation activities were measured for determining the oxidative stress.
The liver levels of MDA and GSH were significantly different between the honey and BDL groups (P = .006 and .001, respectively). However, there was no significant difference between the plasma MDA and GSH levels of these groups (P > .05). In group III, significant reductions in the size of enlarged hepatocytes and the edema were demonstrated. The dilatation of the bile canaliculi dramatically turned to original dimention. By TUNEL assay, it was shown that administration of honey decreased the number of apoptotic cells.
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Regular ArticleObstructive Jaundice Impairs Reticuloendothelial Function and Promotes Bacterial Translocation in the Rat

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Regular Article
Obstructive Jaundice Impairs Reticuloendothelial Function and Promotes Bacterial Translocation in the Rat