Deconvolution of the fluorescence spectra measured through a needle probe to assess the functional state of the liver.

OBJECTIVES: Currently, one of the most pressing issues for surgeons in the treatment of obstructive jaundice is the ability to assess the functional state of the liver and to detect and determine the degree of liver failure in a timely manner with simple and objective techniques. In this regard, the use of fluorescence spectroscopy method can be considered as one of the ways to improve the informativity of existing diagnostic algorithms in clinical practice and to introduce new diagnostic tools. Thus, the aim of the work was to study in vivo the functional state of liver parenchyma by the method of fluorescence spectroscopy implemented through a needle probe and assess the contribution of the main tissue fluorophores to reveal new diagnostic criteria. MATERIALS AND METHODS: We compared data from 20 patients diagnosed with obstructive jaundice and 11 patients without this syndrome. Measurements were performed using a fluorescence spectroscopy method at excitation wavelengths of 365 and 450 nm. Data were collected using a 1 mm fiber optic needle probe. The analysis was based on the comparison of the results of deconvolution with the combinations of Gaussian curves reflecting the contribution of the pure fluorophores in the liver tissues. RESULTS: The results showed a statistically significant increase in the contribution of curves reflecting NAD(P)H fluorescence, bilirubin, and flavins in the group of patients with obstructive jaundice. This and the calculated redox ratio values indicated that the energy metabolism of the hepatocytes may have shifted to glycolysis due to hypoxia. An increase in vitamin A fluorescence was also observed. It may also serve as a marker of liver damage, indicating impaired vitamin A mobilization from the liver due to cholestasis. CONCLUSIONS: The results obtained reflect changes associated with shifts in the content of the main fluorophores characterizing hepatocyte dysfunction caused by accumulation of bilirubin and bile acids and after disturbance of oxygen utilization. The contributions of NAD(P)H, flavins, and bilirubin as well as vitamin A can be used for further studies as promising diagnostic and prognostic markers for the course of liver failure. Further work will include collecting fluorescence spectroscopy data in patients with different clinical effects of obstructive jaundice on postoperative clinical outcome after biliary decompression.

Time-Related Evidence of Intestinal Oxidative Stress in Obstructive Jaundice-Induced Rats.

INTRODUCTION: Obstructive jaundice is known to affect intestinal permeability and facilitate bacterial translocation through related mechanisms. This study was conducted to evaluate the alterations concerning blood biochemistry and levels of several markers of oxidative stress (OS) in blood and intestinal mucosa caused by obstructive jaundice and how these fluctuate over time, in order to further explore the possibility of intervening in the OS path in future experiments. METHODS: A total of 54 albino Wistar rats were randomly divided into three groups (control, sham operated, and bile duct ligation) and sacrificed at specific time intervals (12 h and 2, 7, and 14 days). The intestinal barrier function was evaluated by measuring endotoxin levels in portal, aortic, and peripheral blood. Also, basic biochemical parameters were simultaneously measured in peripheral blood. Tissue samples collected from the terminal ileum were homogenized for determining the OS markers, lipid peroxidation, and protein-free radical-induced oxidation. RESULTS: We designed this experiment to examine the alterations in enteric mucosa primarily in relation to OS in a period of 14 days. During this time period, we investigated in specific time intervals not only OS fluctuations but also other liver function parameters, as well as CRP and endotoxin levels. The alterations were monitored in relation to time after bile duct ligation. CONCLUSION: Bile duct ligation in rats causes OS versus post-ligation time progression of the common bile duct. OS was increased by ∼50% compared to control/sham and peaked at 7 days and at least up to 14 days post-ligation. This phenomenon was accompanied with a deranging of liver function after ligation, as anticipated, but not in all measured parameters; biochemical and endotoxin levels followed the same pattern.

The pathogenesis of renal injury in obstructive jaundice: A review of underlying mechanisms, inducible agents and therapeutic strategies.

Kidney injury is one of the main complications of obstructive jaundice (OJ) and its pathogenesis has not been clarified. As an independent risk factor for OJ associated with significant morbidity and mortality, it can be mainly divided into two types of morphological injury and functional injury. We called these dysfunctions caused by OJ-induced kidney injury as OJKI. However, the etiology of OJKI is still not fully clear, and research studies on how OJKI becomes a facilitated factor of OJ are limited. This article reviews the underlying pathological mechanism from five aspects, including metabolisms of bile acids, hemodynamic disturbances, oxidative stress, inflammation and the organic transporter system. Some nephrotoxic drugs and measures that can enhance or reduce the renal function with potential intervention in perioperative periods to alleviate the incidence of OJKI were also described. Furthermore, a more in-depth study on the pathogenesis of OJKI from multiple aspects for exploring more targeted treatment measures were further put forward, which may provide new methods for the prevention and treatment of clinical OJKI and improve the prognosis.

Distribution of the organic anion transporters Oat1 and Oat3 between renal membrane microdomains in obstructive jaundice.

Relation between the renal function and the membrane environment where the organic anion transporters Oat1 and Oat3 are localized is scarce. The aim of this study was to examine the Oat1 and Oat3 distribution in different cellular fractions under physiological conditions as well as the effects of extrahepatic cholestasis on membrane distribution of both proteins. Besides, the potential role of jaundice serum on the Oat1 and Oat3 expression in suspensions of renal tubular cells was evaluated. Cellular and membrane fractions of renal cortex were obtained from control rats to evaluate Oat1 and Oat3 protein expressions. Other rats were subjected to bile duct ligation (BDL) or Sham operation to determine the membrane distribution of Oat1 and Oat3 between lipid raft domains (LRD) and non-LRD. Incubation of renal cortical cells with serum from Sham and BDL were also performed to study Oat1 and Oat3 protein expressions. In physiological conditions, Oat1 and Oat3 were concentrated in LRD. The pathology induced a shift of Oat1 from LRD to non-LRD, while Oat3 showed no changes in its distribution. In cells exposed to BDL serum, Oat1 protein expression in membranes significantly increased. For Oat3, no difference between groups was observed. The Oat1 redistribution to non-LRD in BDL could be favoring the increase in renal transport of organic anions previously observed. This change was specific to Oat1. The in vitro experiment allows to conclude that some component present in BDL serum is responsible for the alterations observed in Oat1 expression in cortical membranes.

MicroRNA-29a mitigation of toll-like receptor 2 and 4 signaling and alleviation of obstructive jaundice-induced fibrosis in mice.

Cholestasis and hepatitis can cause continuous liver damage that may ultimately result in liver fibrosis. In a previous study, we demonstrated that microRNA-29a (miR-29a) protects against liver fibrosis. Toll-like receptor 2 (TLR2) and TLR4 are pattern recognition receptors of bacterial lipoprotein and lipopolysaccharide, both of which participate in activating hepatic stellate cells and liver fibrosis. The purpose of this study is to characterize the biological influence of miR-29a on TLR2 and TLR4 signaling in livers injured with bile duct ligation (BDL). We performed BDL on both miR-29a transgenic mice (miR-29aTg) and wild-type mice to induce cholestatic liver injury. Primary HSCs were transfected with a miR-29a mimic and inhibitor. In the wild-type mice, the BDL demonstrated significant α-smooth muscle actin fibrotic matrix formation and hepatic high mobility group box-1 expression. However, in the miR-29aTg mice, these factors were significantly reduced. Furthermore, miR-29a overexpression reduced the BDL exaggeration of TLR2, TLR4, MyD88, bromodomain-containing protein 4 (BRD4), phospho-p65 as well as proinflammatory cytokines, IL-1ß, MCP-1, TGF-ß, and TNF-α. In vitro, miR-29a mimic transfection reduced α-SMA, BRD4,TLR2, and TLR4 expressions in HSCs. This study provides new molecular insight into the ability of miR-29a to inhibit TLR2 and TLR4 signaling, which thus slows the progression of cholestatic liver deterioration.

Resveratrol Protects Oxidative Stress-Induced Intestinal Epithelial Barrier Dysfunction by Upregulating Heme Oxygenase-1 Expression.

BACKGROUND/AIM: Obstructive jaundice (OJ) is frequently complicated by infections and has been associated with increased bacterial translocation, intestinal epithelial hyperpermeability, and oxidative stress, but the mechanism remains unclear. The potential effect of resveratrol (Res) on modifying intestinal epithelial dysfunction was evaluated both in vitro and in vivo. METHODS: Caco-2 cells (in vitro) and male Wistar rats (n = 60; in vivo) were used to evaluate the role of Res on intestinal epithelial dysfunction. Hydrogen peroxide was used to induce oxidative stress in the Caco-2 cells. In bile duct-ligated group, OJ was successfully established on Day 7 after bile duct ligation, whereas sham-operated and vehicle-treated rats served as controls. Western blot and RT-qPCR were performed to analyze TJ proteins expression in epithelium isolated from rat intestine. RESULTS: Intestinal hyperpermeability was associated with decreased expression and phosphorylation of occludin and zonula occluden (ZO-1), but increased oxidation in Caco-2 cells and the intestinal epithelium. Res treatment increased the epithelial expression and phosphorylation of occludin and ZO-1 in a concentration-dependent manner. Moreover, Res which protected Caco-2 cells from H2O2-induced oxidative damage clearly reduced malondialdehyde level and intracellular reactive oxygen species accumulation, but increased the expression levels of superoxide dismutase and heme oxygenase-1 (HO-1). Further studies showed that Res also inhibited H2O2-induced protein kinase C activity and p38 phosphorylation. Interestingly, these effects of Res were abolished by the HO-1 inhibitor zinc protoporphyrin or knockdown of HO-1 by siRNA. CONCLUSIONS: Res protected gut barrier function possibly by initiating HO-1-dependent signaling which is essential for common expression of key tight junction proteins. It also provides a rationale to develop Res clinical applications of intestinal disorders.

[ОPTIMIZATION OF PREOPERATIVE PREPARATION AND CONSERVATIVE TREATMENT OF OBTURATION JAUNDICE, OCCURRING ON BACKGROUND OF BILIARY CALCULOUS DISEASE].

Оbturation jaundice (ОJ) on background of biliary calculous disease (BCD) was diagnosed in 61 patients. There was studied the impact of L­lysine escinate and glutargin on the treatment results, which were included in complex of standard preoperative preparation, and what had transformed into conservative treatment and disappearing of ОJ without operative intervention. In accordance to the biochemical investigations results, which characterize a functional state of the liver, OJ had disappeared more rapidly while application of the treatment proposed. Positive results of treatment had witnessed actuality of the trend choosed and necessity of its further studying.

Bile acid-induced cholemic nephropathy.

Kidney injury in deeply jaundiced patients became known as cholemic nephropathy. This umbrella term covers impaired renal function in cholestatic patients with characteristic histomorphological changes including intratubular cast formation and tubular epithelial cell injury. Cholemic nephropathy represents a widely underestimated but important cause of kidney dysfunction in patients with cholestasis and advanced liver disease. However, the nomenclature is inconsistent since there are numerous synonyms used; the underlying mechanisms of cholemic nephropathy are not entirely clear, and widely accepted diagnostic criteria are still missing. Consequently, the current article aims to summarize the present knowledge on the clinical and morphological characteristics, available preclinical models, derived potential pathomechanisms, and future diagnostic and therapeutic strategies in cholemic nephropathy. Furthermore, we provide a potential research agenda for this evolving field.

Nod2 deficiency protects mice from cholestatic liver disease by increasing renal excretion of bile acids.

BACKGROUND & AIMS: Chronic liver disease is characterized by fibrosis that may progress to cirrhosis. Nucleotide oligomerization domain 2 (Nod2), a member of the Nod-like receptor (NLR) family of intracellular immune receptors, plays an important role in the defense against bacterial infection through binding to the ligand muramyl dipeptide (MDP). Here, we investigated the role of Nod2 in the development of liver fibrosis. METHODS: We studied experimental cholestatic liver disease induced by bile duct ligation or toxic liver disease induced by carbon tetrachloride in wild type and Nod2(-/-) mice. RESULTS: Nod2 deficiency protected mice from cholestatic but not toxin-induced liver injury and fibrosis. Most notably, the hepatic bile acid concentration was lower in Nod2(-/-) mice than wild type mice following bile duct ligation for 3 weeks. In contrast to wild type mice, Nod2(-/-) mice had increased urinary excretion of bile acids, including sulfated bile acids, and an upregulation of the bile acid efflux transporters MRP2 and MRP4 in tubular epithelial cells of the kidney. MRP2 and MRP4 were downregulated by IL-1ß in a Nod2 dependent fashion. CONCLUSIONS: Our findings indicate that Nod2 deficiency protects mice from cholestatic liver injury and fibrosis through enhancing renal excretion of bile acids that in turn contributes to decreased concentration of bile acids in the hepatocyte.

MicroRNA-29a protects against acute liver injury in a mouse model of obstructive jaundice via inhibition of the extrinsic apoptosis pathway.

Recent studies have shown that microRNA-29 (miR-29) is significantly decreased in liver fibrosis, as demonstrated in human liver cirrhosis, and that its downregulation influences the activation of hepatic stellate cells. In addition, both cleaved caspase-3 production and apoptosis play a role in cholestatic liver injury. However, it is unknown if miR-29 is effective in modulating the extent of injury. We employed miR-29a transgenic mice (miR-29aTg mice) and wild-type (WT) littermates to clarify the role of miR-29 in hepatic injury and fibrogenesis, using the bile duct-ligation (BDL) mouse model. After BDL, all three members of the miR-29 family were significantly downregulated in the livers of WT mice, and miR-29b and miR-29c were significantly downregulated in the livers of the miR-29aTg mice. Liver function, as measured by alanine transaminase and aspartate transaminase activity, was significantly improved in the miR-29aTg mice than in the WT littermates, following 1 week of obstructive jaundice. In addition, overexpression of miR-29a was associated with a significant downregulation of the expression of collagen-1α1, collagen-4α1, phospho-FADD, cleaved caspase-8, cleaved caspase-3, Bax, Bcl-2, PARP, and nuclear factor-κB, as well as an upregulation of phospho-AKT expression. In addition, there were significantly fewer TUNEL-positive liver cells in the miR-29aTg group than in the WT littermates after BDL. Our results indicate that miR-29a decreases cholestatic liver injury and fibrosis after BDL, at least partially, by modulating the extrinsic rather than intrinsic pathway of apoptosis.

Proteinase-activated receptor 1 contributed to up-regulation of enkephalin in keratinocytes of patients with obstructive jaundice.

BACKGROUND: Skin synthesis of endogenous opioids such as enkephalin is considered to be increased in cholestatic rodents, which may induce antinociception in cholestatic liver disease. No studies have reported yet the expression of skin enkephalin in patients with cholestasis. METHODS: Electrical pain threshold, postoperative morphine consumption, and skin enkephalin expression were measured in patients with jaundice (n = 18) and control patients (n = 16). Male Sprague-Dawley rats (n = 52) and human keratinocyte cell line HaCaT were used in vivo and in vitro studies, respectively. Nociceptive thresholds and plasma and skin levels of methionine-enkephalin were compared in protease-activated receptors-1-antagonized and control bile duct-ligated rats. In in vitro study, the effect on thrombin-induced enkephalin expression was examined and the role of extracellular regulated protein kinases 1/2 and p38 was investigated. RESULTS: The authors found that: (1) the electrical pain threshold (mean ± SD) was 1.1 ± 0.1 mA in control patients, whereas it was significantly increased in patients with jaundice (1.7 ± 0.3 mA); 48-h postoperative morphine consumption was approximately 50% higher in the control group than that in the group with jaundice; (2) Skin keratinocytes enkephalin expression was increased in the patients with jaundice; (3) Protease-activated receptors-1 antagonist 1 µg·kg(-1)·day(-1) treatment to the bile duct-ligated rats significantly reduced plasma levels of methionine-enkephalin, nociceptive thresholds, and keratinocytes enkephalin expression; and (4) protease-activated receptors-1 activation induced enkephalin expression through phosphorylation of extracellular regulated protein kinases 1/2 and p38 in keratinocytes. CONCLUSION: Protease-activated receptors-1 activation in peripheral keratinocytes may play an important role in the local synthesis of enkephalin during cholestasis.

Comparative study of 4 Fr versus 6 Fr nasobiliary drainage catheters: a randomized, controlled trial.

BACKGROUND AND AIM: Despite the benefits of endoscopic nasobiliary drainage (NBD) in endoscopic retrograde cholangiopancreatography (ERCP), post-ERCP pancreatitis (PEP) and nose/throat discomfort can result. We aimed to determine whether the use of a smaller catheter alleviates these complications. METHOD: A randomized, controlled trial at a tertiary care center compared 4 Fr and 6 Fr NBD catheters; 165 ERCP patients with naïve papillae were randomly assigned to a catheter-size group. RESULTS: The prevalence of PEP was significantly lower in the 4 Fr group (3.7%; 3/82) than in the 6 Fr group (15.7%; 13/83; P = 0.019). No spontaneous catheter displacement occurred within 24 h. Discomfort visual analog scores were 2.6 and 4.3 in the 4 Fr and 6 Fr groups, respectively (P = 0.0048) on procedure day; on the following day, the scores were 2.3 and 3.6 (P = 0.028). Bile output was 16.3 mL/h and 21.4 mL/h in the 4 Fr and 6 Fr groups (P = 0.051). On obstructive jaundice subgroup analysis, bile drainage was 19.2 mL/h and 22.1 mL/h in the 4 Fr and 6 Fr groups (P = 0.40). The 4 Fr group required 5.6 days to reduce bilirubin levels versus 6.1 days in the 6 Fr group (P = 0.51). CONCLUSIONS: In patients with naïve papillae, lower rates of PEP and less nose/throat discomfort are associated with the use of 4 Fr NBD catheters. In patients with obstructive jaundice, 4 Fr and 6 Fr catheters are comparable with regard to bile output and bilirubin level reduction.

MAC(EI) and MAC(awake) of sevoflurane in infants with obstructive jaundice.

BACKGROUND: The aim of this study was to determine whether the MACEI and MACawake of sevoflurane in infants with obstructive jaundice are different from that observed in nonjaundiced infants. METHODS: Infants scheduled for abdominal surgery were recruited into the study. General anesthesia was induced with 8% sevoflurane inhaled with 8 l·min(-1) of oxygen via mask, followed by adjustment of inspired sevoflurane to the target concentration based on the result in previous patient at which laryngoscopy and tracheal intubation were attempted and maintained for 15 min. All responses to tracheal intubation were assessed. At the end of the procedure, sevoflurane was titrated to the target concentration, which was kept constant for 15 min before a standard stimulus was applied to determine whether the infant was awake. The Dixon's 'up and down' method was used to determine progression of subsequent concentrations. RESULTS: There was no significant difference between the MACEI of sevoflurane in infants with obstructive jaundice (3.40 ± 0.21%) and that observed in the control group (3.43 ± 0.18%). But the MACawake of sevoflurane in jaundiced infants (1.00 ± 0.15%) was significantly lower than that of nonjaundiced controls (1.40 ± 0.21%; P = 0.004); to complement these findings, we reported a negative correlation between serum total bilirubin and the probability of awakening (OR = 0.984, 95% CI is 0.970-0.998, P = 0.028). CONCLUSIONS: The MACawake of sevoflurane was reduced in obstructive jaundiced infants compared with nonjaundiced controls, whereas there was no significant difference between the MACEI of sevoflurane in infants with obstructive jaundice and that observed in nonjaundiced infants.

Hepatocyte apoptotic index and p53 expression in obstructive jaundice rats.

OBJECTIVE: Obstructive jaundice is a serious disease. It can deteriorate critical functions in the liver. MATERIAL AND METHOD: A total of 20 male Wistar-Albino rats were randomly allocated into two groups consisting of ten in each as follows: Group I (Control) was subjected to a sham operation isolating the bile duct. Group II(Study) was subjected to acute cholestasis induced by bile duct ligation with 4/0 silk suture from two different places and full fold cut between ligatures. On the 7th day, group II rats were re-operated for liver sampling and sacrification-aimed histological analysis through the old incision with anaesthesia. Hepatic tissues were histologically and immunohistochemically processed. The number of apoptotic and p53(+) cells were measured. RESULTS: On the 7th day, the averages of direct and indirect bilirubin values in Group II rats were found to be 6.99 and 11.70 mg/dl, respectively. They were observed to be statistically significant. In the immunohistochemical evaluation p53 expression in hepatocytes was assessed, p53-positive hepatocytes were determined to exist quite widely in the tissue samples taken from the livers of rats in the study group. Nevertheless, no cells exhibiting p53 expression were found in the tissue samples of the control group. CONCLUSION: Apoptosis is a closed box and it might make it possible to stop the many disease processes or accelerate the healing. If the principal effective mechanism in the liver under a certain stress factor is apoptosis, it is definite that it will make a difference in the treatment approach. Consequently, we can say that both apoptotic index and p53 expression increase in the rats' liver with biliary obstruction (Fig. 4, Ref. 51).

FXR contributes to obstructive jaundice-induced vascular hyporeactivity in mesenteric arteries by reconstituting BKCa channels.

OBJECTIVE: Vascular hyporeactivity increases with the incidence of obstructive jaundice (OJ). Evidence suggests that OJ activates the farnesoid X receptor (FXR) as well as the large-conductance Ca2+-activated K+ (BKCa or MaxiK) channel. This study was designed to explore the role of the FXR in vascular hyporesponsiveness induced by cholestasis. METHODS: The OJ model rats were constructed by bile duct ligation (BDL) and treated with an FXR agonist or antagonist. Vasoconstriction of the mesenteric arteries (MAs) was assessed in vitro. Whole-cell patch clamp recordings were used to investigate BKCa channel function. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect mRNA and protein levels. RESULTS: A significant increase in vascular tone and responsiveness to norepinephrine (NE) was observed after the MaxiK channel blocker (IbTX) was administered. This effect was pronounced in BDL animals and can be mimicked by the FXR agonist GW4064 and inhibited by the FXR antagonist Z-guggulsterone (Z-Gu). GW4064 has a similar effect as cholestasis in promoting MaxiK currents in isolated arterial smooth muscle cells (ASMCs), while Z-Gu blunted this effect. The mRNA and protein expression of FXR and MaxiK-ß1, but not MaxiK-α, were significantly increased in the BDL group in comparison to the sham. Furthermore, activation or inhibition of FXR promoted or inhibited the mRNA and protein expression of the MaxiK-ß1 subunit, respectively. CONCLUSION: Activation of FXR enhances the capability of the MaxiK channel to regulate vascular tone and leads to vascular hyporesponsiveness in the MAs of BDL rats, which may be mediated by the nonparallel upregulation of MaxiK-α and MaxiK-ß1 subunit expression.

Selective activation of Toll-like receptor 7 in activated hepatic stellate cells may modulate their profibrogenic phenotype.

Cholestatic liver injury may activate HSCs (hepatic stellate cells) to a profibrogenic phenotype, contributing to liver fibrogenesis. We have previously demonstrated the involvement of TLR (Toll-like receptor) 7 in the pathogenesis of biliary atresia. In the present study we investigated the ability of TLR7 to modulate the profibrogenic phenotype in HSCs. Obstructive jaundice was associated with significant down-regulation of TLR7. Primary HSCs isolated from BDL (bile duct ligation) rats with obstructive jaundice exhibited reduced expression of TLR7 and increased expression of α-SMA (α-smooth muscle actin) and collagen-α1 compared with sham rats, reflecting HSC-mediated changes. Treatment of primary activated rat HSCs and rat T6 cells with CL075, a TLR7 and TLR8 ligand, significantly decreased expression of MCP-1 (monocyte chemotactic protein-1), TGF-ß1 (transforming growth factor-ß1), collagen-α1 and MMP-2 (matrix metalloproteinase-2), and inhibited cell proliferation and migration. In contrast, silencing TLR7 expression with shRNA (short hairpin RNA) in T6 cells effectively blocked the effects of CL075 stimulation, reversing the changes in MCP-1, TGF-ß1 and collagen-α1 expression and accelerating cell migration. Our results indicate that obstructive jaundice is associated with down-regulation of TLR7 and up-regulation of profibrogenic gene expression in HSCs. Selective activation of TLR7 may modulate the profibrogenic phenotype in activated HSCs associated with cholestatic liver injury.

The protective effect of ellagic acid on lung damage caused by experimental obstructive jaundice model.

AIM: This study aimed to investigate protective effects of ellagic acid on lungs in an experimental obstructive jaundice model. METHODS: Four groups were established, each consisting of ten randomly selected rats: Group 1: sham, Group 2: ellagic acid, Group 3: obstructive jaundice, and Group 4: obstructive jaundice + ellagic acid. Ellagic acid was administered orally at a dose of 60 mg/kg/day to group 2 and 4. The animals were sacrificed eight days later. The total oxidative status and the total antioxidant capacity in their lung tissue were determined, and malondialdehyde levels in their blood were measured. Histopathological changes in the lungs were examined. RESULTS: In the obstructive jaundice group treated with ellagic acid, there was a decrease in malondialdehyde levels and a reduction in the total oxidative status and the oxidative stress index, whereas the total antioxidant capacity increased (p < 0.001). The histopathological examination showed that neutrophil leukocyte infiltration and edema formation decreased and destruction of lung parenchyma disappeared following the treatment with the ellagic acid (p < 0.05). CONCLUSION: This study shows that ellagic acid has a protective effect against oxidative damage in lung tissue in obstructive jaundice.

Obstructive jaundice activates nitroxidergic neurons of the vago-vagal neural circuit that regulates the hepatobiliary system in rabbits.

In this study, we investigated the expression of neuronal nitric oxide synthase (nNOS) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), two specific enzymes for nitric oxide (NO) synthesis, in the development of liver fibrosis induced by chronic bile duct ligation (BDL) in the rabbit. We specifically studied the liver-innervated nitroxidergic neurons that originate in the nodose ganglion (NG), nucleus of the solitary tract (NTS) and dorsal motor vagal nucleus (DMV). Our data showed that BDL resulted in overexpression of NADPH-d/nNOS in the NG, NTS and DMV neurons. Using densitometric analysis, we found a significant increase in NADPH-d expression as a result of BDL in the NG, NTS and DMV (72.6, 79.4 and 57.4% increase, respectively). These findings were corroborated by serum biochemistry and hepatic histopathological examination, which were influenced by NADPH-d/nNOS-generated NO in the liver following BDL. Upregulation of NADPH-d/nNOS expression may have important implications, including (1) facilitation of extrahepatic biliary parasympathetic tone that promotes gallbladder emptying of excess stagnant bile; (2) relaxation of smooth muscles of bile canaliculi thus participating in the pathogenesis of cholestasis; (3) dilation of hepatic sinusoids to counter BDL-induced intrahepatic portal hypertension in which endothelia may be damaged, and (4) alterations in hepatic metabolism, such as glycogenesis, bile formation and secretion, and bilirubin clearance.

Endocrine cells in the human common bile duct in patients with obstructive jaundice.

BACKGROUND/AIMS: There was no data about endocrine cells in the extrahepatic bile duct in secondary cholangitis due to obstructive jaundice. The aim of the present study is to investigate immunohistochemically the endocrine cell types in the lower part of the human common bile duct in biopsy samples, collected during drainage because of complete or incomplete obstruction, caused mainly by stones. We explained the presence of various hormone-producing endocrine cells in this region with the regulation of physiological and pathological processes there. METHODOLOGY: We used light and electron microscopic immunohistochemistry. RESULTS: More gastrin-positive, somatostatin-positive, secretin-positive, serotonin-positive, chromogranin- A-positive and synaptophysin-positive endocrine cells were found compared to control preparations. CONCLUSIONS: Occurrence of endocrine cells may relate to disturbed bile flow and to formation of calculi. Endocrine cell hyperplasia may be related to longstanding inflammation as in chronic cholecystitis and all secreted hormones from the described ECs can support pathologic process in the choledochus, i.e. inflammation, increased mucus secretion, fibrosis, muscle contraction, etc. We may state that various ECs (similar to those in duodenum) present in the lower part of the large bile duct and their hormones exert action on physiology (motility, secretion) and pathology (inflammation and fibrosis) in that part of the biliary tree.