Correlation of inflammation parameters and biochemical markers of cholestasis with the intensity of lipid peroxidation in patients with choledocholithiasis.

BACKGROUND/AIM During choledocholitiasis inflammatory oxidant stress involves the promotion of mitochondrial dysfunction through an intracellular oxidant stress in hepatocytes leading mainly to necrosis and less to apoptosis. The product of oxidative stress, malondialdehyde (MDA), is extremely cytotoxic and damages cell membranes and intracellular macromolecules. The toxicity of MDA is based on its ability to act as a mutagenic agent in a cell. Therefore, the aim of this prospective study was to establish correlation of the parameters of inflammation and biochemical markers of cholestasis with the intensity of oxidative stress in pathogenesis of liver function disorders. METHODS Seventy adult subjects of either sex included in the study were devided into two groups: I--40 patients with obstructive icterus caused by choledocholithiasis, and II--30 healthy individuals. All the participants were subjected to a clinical, laboratory and ultrasonic check-up at the Internal Department of the Military Hospital in Nis. The parameters of oxidative stress: MDA, a measure of lipid peroxidation, and inflammation parameters: C-reactive protein (CRP), fibrinogen, albumins, number of leukocytes (Leu), granulocytes (Gr), lymphocytes (Ly) and monocytes (Mo) and biochemical markers of cholestasis: activity of gamma-glutamyltransferase (gamma-GT) and alkaline phosphatase (AP) enzymes, the level of total, direct and indirect bilirubin were determined by standard biochemical methods. RESULTS Lower values of albumin (p < 0.001), and significantly higher values of fibrinogen (p < 0.05) and CRP (p < 0.001) were found in the blood of the patients with cholestasis due to choledocholithiasis in relation to the controls. Significantly higher values of Leu (p < 0.01) and Gr (p < 0.001) with decreasing number of Ly (p < 0.001) and Mo (p < 0.001) were found in blood of the patients with cholestasis due to choledocholithiasis in relation to the control. Similarly, higher values of gamma-GT, and AP (p < 0.001), as well as the level of total, direct and indirect bilirubin (p < 0.001) were found in blood of the patients with cholestasis due to choledocholithiasis in relation to the controls. The concentration of MDA (p < 0.001) was increased in the patients with choledocholithiasis in relation to the controls. There was a significant positive linear correlation of the number of leukocytes (r = 0.51, p < 0.05) and the concentration of total (r = 0.87, p < 0.01), direct (r = 0.85, p < 0.01) and indirect (r = 0.88, p < 0.01) bilirubin with the concentration of MDA in the group of patients with choledocholithiasis. CONCLUSION Neutrophils and the levels of total, direct and indirect bilirubin have a significant positive linear correlation with the level of lipid peroxidation in patients with choledocholithiasis. Neutrophilia and hiperbilirubinemia observed in this way represent important parameters in estimating the level of liver tissue damage in choledocholithiasis.

[1]  P. Staňková,et al.  Deteriorating effect of fluvastatin on the cholestatic liver injury induced by bile duct ligation in rats. , 2011, General physiology and biophysics.

[2]  Hartmut Jaeschke,et al.  Reactive oxygen and mechanisms of inflammatory liver injury: Present concepts , 2011, Journal of gastroenterology and hepatology.

[3]  H. Jaeschke,et al.  Bile acids induce inflammatory genes in hepatocytes: a novel mechanism of inflammation during obstructive cholestasis. , 2011, The American journal of pathology.

[4]  Samuel S. Lee,et al.  Mechanisms of TNFα-induced cardiac dysfunction in cholestatic bile duct-ligated mice: Interaction between TNFα and endocannabinoids , 2010 .

[5]  César Berzosa,et al.  Melatonin protects against taurolithocholic‐induced oxidative stress in rat liver , 2010, Journal of cellular biochemistry.

[6]  Yousheng Li,et al.  Ethyl pyruvate prevents intestinal inflammatory response and oxidative stress in a rat model of extrahepatic cholestasis. , 2010, The Journal of surgical research.

[7]  H. Jaeschke,et al.  Oxidative Stress and the Pathogenesis of Cholestasis , 2010, Seminars in liver disease.

[8]  R. Stockley,et al.  Studies of Gamma-Glutamyl Transferase in Alpha-1 Antitrypsin Deficiency , 2010, COPD.

[9]  Samuel S. Lee,et al.  Mechanisms of TNFalpha-induced cardiac dysfunction in cholestatic bile duct-ligated mice: interaction between TNFalpha and endocannabinoids. , 2010, Journal of hepatology.

[10]  S. Norton,et al.  A study of preoperative factors associated with a poor outcome following laparoscopic bile duct exploration , 2010, Surgical Endoscopy.

[11]  Z. Ďuračková Some current insights into oxidative stress. , 2010, Physiological research.

[12]  U. Ozel Turkcu,et al.  Effects of carbon dioxide pneumoperitoneum on hepatic function in obstructive jaundice: an experimental study in a rat model , 2010, Langenbeck's Archives of Surgery.

[13]  D. Rockey,et al.  Liver test patterns in patients with acute calculous cholecystitis and/or choledocholithiasis , 2009, Alimentary pharmacology & therapeutics.

[14]  G. Mai,et al.  Pancreaticoduodenectomy With Preoperative Obstructive Jaundice: Drainage or Not , 2009, Pancreas.

[15]  J. Clària,et al.  Mecanismos básicos de lesión hepatocelular. Papel de los mediadores lipídicos de inflamación , 2008 .

[16]  M. Aller,et al.  Experimental obstructive cholestasis: the wound-like inflammatory liver response , 2008, Fibrogenesis & tissue repair.

[17]  M. Miyazaki,et al.  Excessive inflammation but decreased immunological response renders liver susceptible to infection in bile duct ligated mice. , 2008, The Journal of surgical research.

[18]  I. Rubinfeld,et al.  Hyperbilirubinemia: a risk factor for infection in the surgical intensive care unit. , 2008, American journal of surgery.

[19]  J. Clariá,et al.  [Basic mechanisms of hepatocellular injury. Role of inflammatory lipid mediators]. , 2008, Gastroenterologia y hepatologia.

[20]  N. Gharbi,et al.  Antioxidant enzymes activities and bilirubin level in adult rat treated with lead. , 2007, Comptes rendus biologies.

[21]  E. Heathcote Diagnosis and management of cholestatic liver disease. , 2007, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[22]  J. Grönroos,et al.  Stone or stricture as a cause of extrahepatic cholestasis – do liver function tests predict the diagnosis? , 2006, Clinical chemistry and laboratory medicine.

[23]  C. Vagianos,et al.  Evidence for intestinal oxidative stress in patients with obstructive jaundice , 2006, European journal of clinical investigation.

[24]  T. L. Deem,et al.  Unconjugated Bilirubin Inhibits VCAM-1-Mediated Transendothelial Leukocyte Migration1 , 2005, The Journal of Immunology.

[25]  H. Jaeschke,et al.  Functional importance of ICAM-1 in the mechanism of neutrophil-induced liver injury in bile duct-ligated mice. , 2004, American journal of physiology. Gastrointestinal and liver physiology.

[26]  W. Reinhart,et al.  Impairment of blood rheology by cholestatic jaundice in human beings. , 2003, The Journal of laboratory and clinical medicine.

[27]  M. Matsuda,et al.  Edaravone, a Novel Free Radical Scavenger, Prevents Liver Injury and Mortality in Rats Administered Endotoxin , 2003, Journal of Pharmacology and Experimental Therapeutics.

[28]  E. Giamarellos‐Bourboulis,et al.  Systemic endotoxaemia following obstructive jaundice: the role of lactulose. , 2003, The Journal of surgical research.

[29]  H. Jaeschke,et al.  Neutrophils aggravate acute liver injury during obstructive cholestasis in bile duct–ligated mice , 2003, Hepatology.

[30]  S. Kawasaki,et al.  Results of Surgical Resection for Patients With Hilar Bile Duct Cancer: Application of Extended Hepatectomy After Biliary Drainage and Hemihepatic Portal Vein Embolization , 2003, Annals of surgery.

[31]  S. Muhtaroğlu,et al.  The Effects of Dimethylsulfoxide in Experimental Obstructive Jaundice , 2003, Acta chirurgica Belgica.

[32]  J. Collier,et al.  How to respond to abnormal liver function tests. , 2002, Clinical medicine.

[33]  J. Boyer,et al.  Adaptive regulation of bile salt transporters in kidney and liver in obstructive cholestasis in the rat. , 2001, Gastroenterology.

[34]  Bente Klarlund Pedersen,et al.  Aging and proinflammatory cytokines , 2001, Current opinion in hematology.

[35]  R. Sokol,et al.  Bile acid‐induced rat hepatocyte apoptosis is inhibited by antioxidants and blockers of the mitochondrial permeability transition , 2001, Hepatology.

[36]  S. Ghosh,et al.  Molecular mechanisms of NF-κB activation induced by bacterial lipopolysaccharide through Toll-like receptors: , 2000 .

[37]  M. Miyazaki,et al.  Obstructive jaundice impairs hepatic sinusoidal endothelial cell function and renders liver susceptible to hepatic ischemia/reperfusion. , 2000, Journal of hepatology.

[38]  K. Matsumoto,et al.  Induction of heme oxygenase-1 suppresses venular leukocyte adhesion elicited by oxidative stress: role of bilirubin generated by the enzyme. , 1999, Circulation research.

[39]  M. Margaglione,et al.  Fibrinogen Plasma Levels in an Apparently Healthy General Population – Relation to Environmental and Genetic Determinants , 1998, Thrombosis and Haemostasis.

[40]  W. Sha Regulation of Immune Responses by NF-κB/Rel Transcription Factors , 1998, The Journal of experimental medicine.

[41]  P. Kamath Clinical approach to the patient with abnormal liver test results. , 1996, Mayo Clinic proceedings.

[42]  E. Ah-Sing,et al.  Antioxidant defenses in the bile duct-ligated rat. , 1992, Gastroenterology.

[43]  大川 博,et al.  Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction , 1979 .