Taurine protects transplanted liver against ischemia-reperfusion injury

Although liver transplantation as a treatment of end-stage liver disease has developed rapidly, the problem of ischemia-reperfusion injury [I/RI] to the liver graft remains an obstacle. After I/R, Kupffer cells were activated and generate reactive oxygen species [ROS] which play a central role in the pathogenesis of rejection. Taurine is a cysteine derivative known as being a conjugate to primary bile acids; besides oxidative regulation functions, it is supposed to have protective efficacy on ischemia reperfusion liver damage and its anti-hepatic injury may be mainly related to inhibiting lipid peroxides formation, regulating cellular calcium homeostasis and stabilizing biological membrane. To evaluate the effect of taurine injection before liver transplantation on the oxidant [MDA] /antioxidant [reduced glutathione and glutathione peroxidase] status, activation of Kupffer cell [tumor necrosis factor-alpha] and cell apoptosis [expression of hypoxia inducible factor-1 alpha [HIF-1 alpha] and caspase-3]. Forty patients undergoing liver transplantation were divided into two groups: Group I: Taurine group [n=20] were given [1 gm taurine intravenous bolus to the donor 30 min before hepatectomy and another 1 gm to recipient 15 min before graft reperfusion] .Group II: saline control group [n= 20] were given physiological saline of the same volume as taurine group. Liver biopsy was taken before the end of operation for the mRNA expression of HIF-1 alpha and caspase-3. Blood samples were taken from each participant at the beginning of the operation [T[0]], clamping of portal vein [T[1]], 1 h and 3 h after portal vein reperfusion [T[2] and T[3], respectively]. Serum levels of aspartate aminotransferase [AST], alanine aminotransferase [ALT], tumor necrosis factor-alpha [TNF- alpha], malondialdehyde [MDA], reduced glutathione [GSH] and whole blood glutathione peroxidase activity [GPx] were analyzed. TNF-alpha and MDA levels were significantly increased at T[1], significantly peaked at 1 h after reperfusion [T[2]] and significantly decline after 3h [T[3]]. However, this elevation of TNF-alpha and MDA levels were significantly higher in saline group compared to taurine group. On the other hand, the level of GSH and the activity of GPx were significantly higher in the taurine group than in the control group. HIF-1 alpha and caspase-3 mRNA were highly expressed in control group more than taurine group. Taurine can protect the liver against ischemia-reperfusion injury by downregulation of HIF-1alpha, caspase-3, decreasing the production of TNF-alpha and improvement of hepatic antioxidant capacity

Serum neopterin and zinc levels as biological markers of the HCV disease progression

In chronic hepatitis C virus [HCV] infection, both oxidative stress and the effectiveness of the host immune response contribute to its progression to cirrhosis and the development of hepatocellular carcinoma [HCC]. Neopterin is produced by monocyte-derived macrophages after stimulation with interferon-gamma [IFN- gamma] released from activated T- lymphcytes or other immune activators. High neopterin production is associated with increased production of reactive oxygen species [ROS]. Zinc plays an important role in cell-mediated immune function and it has also anti inflammatory and antioxidant properties which can neutralize free radicals and may protect liver cells from the potential damage they cause. To investigate the relationship between serum levels of neopterin and immune-regulated micronutrients [Zn] with chronic HCV infection progression mediated by increased cellular oxidative stress [malondialdehyde, MDA]. The study included 60 subjects that were divided into two groups: Group I comprised 40 chronic HCV patients further subdivided according to liver biopsy inflammatory grading into: 18 patients with mild active hepatitis [Ia], 16 patients with moderate active hepatitis [Ib] and 6 patients with liver cirrhosis [Ic]. Group II comprised 20 healthy volunteers as control. Serum Zinc was measured by atomic absorption spectrophotometer [AAS], neopterin by ELISA and MDA by colorimetric method. Serum levels of neopterin and MDA were detected significantly higher in HCV patients than controls. A significant positive correlation was detected between the levels of both markers with the levels of total bilirubin, AST, ALT in HCV patients. Serum levels of neopterin and MDA were significantly elevated in group Ib and Ic HCV patients compared with group la patients, significant low serum level of zinc were detected in HCV patients than controls and were significantly lower in group Ib and Ic HCV patients than group Ia patients. Serum zinc, neopterin and MDA levels may be valuable biomarkers for the assessment of severity of viral hepatic damage in HCV infection

Biomarkers of the pathogenesis of metabolic syndrome

To investigate the association between oxidant/anti-oxidant balance [MDA and paraoxonase] with the degree of severity of metabolic syndrome [MS] that was measured by the pro/anti-inflammatory markers [TNF-alpha and adiponectin] and other clinical and biochemical criteria to find biomarkers identifying patients at risk for cardiovascular disease [CVD]. The study included eighty patients [20 obese diabetics, 20 non-obese diabetics. 20 obese non-diabetics and 20 controls]. Serum levels of adiponectin and TNF-allpha, were analyzed by ELIZA. MDA and paraoxonase activity [PON] were determined by colorimetric method in all patients with or without MS. The international Diabetes Federation [IDF] proposal identified a greater percentage of MS. The highest prevalence was found in females. Serum levels of adiponectin and paraoxonase activity were significantly decreased but serum levels of TNF-alpha and MDA were significantly increased in MS subjects. There was an inverse correlation between number of features of metabolic syndrome [BMI, waist circumference, fasting plasma glucose, fasting insulin, insulin resistance, blood pressure, TGs and LDL] and protective markers [serum adiponectin and paraxonase levels]. Positive correlation existed with serum TNF-alpha and MDA levels. Metabolic syndrome patients had a higher accumulate [from 3/25 to 9/25 to 13/25]. Triglycerides and TG/HDL-C ratio were significantly positively correlated with TNF-alpha and negatively correlated with adiponectin. Hypoadiponectemia and decreased paraoxonase are associated with higher degree of metabolic alterations of MS. These could be contributing factors to the increased incidence and severity of CVD. These markers levels were significantly changed before accumulation of metabolic criteria indicating their role in production of metabolic syndrome