SciCombinator

Discover the most talked about and latest scientific content & concepts.

Concept: Liver function tests

28

Gallic acid, a polyphenyl class natural product from gallnut and green tea, is known to be antioxidant, anti-inflammatory and radical scavenger. In this study, we aimed to investigate the possible protective effects of gallic acid on paraoxonase and arylesterase activities in liver exposed to acute alcohol intoxication. Paraoxonase and arylesterase activities in liver tissue and serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase levels were measured. Histological investigations were also made. In our study, we observed a significant increase of serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, which are indicators of liver damage after acute ethanol consumption. Gallic acid therapy has significantly reduced the increase in these biomarkers, indicating a possible hepatoprotective effect of gallic acid. Ethanol consumption caused a significant decrease in liver paraoxonase activity (P < 0.001). Gallic acid treatment partly restored this decreased paraoxonase activity, which resulted from ethanol administration. A gallic acid dose of 100 mg/kg was observed as highest restoring effect for paraoxonase activity (P < 0.05). The activity of arylesterase was decreased in the ethanol group as compared with the control group, but this was not significant. However, 50 mg/kg of gallic acid treatment restored the loss of this activity due to ethanol exposure (P < 0.001). We observed that gallic acid ameliorates the liver damage caused by excessive alcohol consumption in a dose-dependent way. Our results in this study showed that gallic acid might have a protective effect against alcoholic liver disease. Copyright © 2012 John Wiley & Sons, Ltd.

Concepts: Alcohol, Ethanol, Liver, Alcoholism, Liver function tests, Hepatology, Lactate dehydrogenase, Alcohol intoxication

28

Hepatic fibrosis is a dynamic chronic liver disease occurring as a consequence of wound-healing responses to various hepatic injuries. This disorder is one of primary predictors for liver-associated morbidity and mortality worldwide. To date, no pharmacological agent has been approved for hepatic fibrosis or could be recommended for routine use in clinical context. Cellular and molecular understanding of hepatic fibrosis has revealed that peroxisome proliferator-activated receptor-γ (PPARγ), the functioning receptor for antidiabetic thiazolidinediones, plays a pivotal role in the pathobiology of hepatic stellate cells (HSCs), whose activation is the central event in the pathogenesis of hepatic fibrosis. Activation of PPARγ inhibits HSC collagen production and modulates HSC adipogenic phenotype at transcriptional and epigenetic levels. These molecular insights indicate PPARγ as a promising drug target for antifibrotic chemotherapy. Intensive animal studies have demonstrated that stimulation of PPARγ regulatory system through gene therapy approaches and PPARγ ligands has therapeutic promise for hepatic fibrosis induced by a variety of etiologies. At the same time, thiazolidinedione agents have been investigated for their clinical benefits primarily in patients with nonalcoholic steatohepatitis, a common metabolic liver disorder with high potential to progress to fibrosis and liver-related death. Although some studies have shown initial promise, none has established long-term efficacy in well-controlled randomized clinical trials. This comprehensive review covers the 10-year discoveries of the molecular basis for PPARγ regulation of HSC pathophysiology and then focuses on the animal investigations and clinical trials of various therapeutic modalities targeting PPARγ for hepatic fibrosis.

Concepts: Pharmacology, Medicine, Gene, Clinical trial, Cirrhosis, Liver function tests, Liver disease, Hepatic stellate cell

28

This study investigated the effects of low-level laser therapy (LLLT) in the liver function, structure and inflammation in a experimental model of carbon tetrachloride (CCl(4) )-induced liver cirrhosis. Wistar rats were divided into Control, LLLT, CCl(4) and CCl(4) +LLLT groups. CCl(4) groups received CCl(4) (0.4 g kg(-1) ; i.p.), three times a week, for 12 weeks. A 830 nm LLLT was performed with a continuous wave, 35 mW, 2.5 J cm(-2) per point, applied to four points of the liver (right and left upper and lower extremities, in the four lobes of the liver) for 2 weeks. Liver structure and inflammation (cirrhotic areas, collagen deposition, inflammation, density of Kupffer and hepatic stellate cells) and function (aspartate aminotransferase, alkaline phosphatase, gamma glutamyltransferase, lactate dehydrogenase, total proteins and globulins) were evaluated. LLLT significantly reduced CCl(4) -increased aspartate aminotransferase (P < 0.001), alkaline phosphatase (P < 0.001), gamma-glutamyl transferase (P < 0.001) and lactate dehydrogenase (P < 0.01) activity, as well as total proteins (P < 0.05) and globulins (P < 0.01). LLLT also reduced the number of cirrhotic areas, the collagen accumulation and the hepatic inflammatory infiltrate. Of note, LLLT reduced CCl(4) -increased number of Kupffer cells (P < 0.05) and hepatic stellate cells (P < 0.05). We conclude that LLLT presents beneficial effects on liver function and structure in an experimental model of CCl(4) -induced cirrhosis.

Concepts: Enzyme, Glucose, Cirrhosis, Liver, Liver function tests, Bilirubin, Hepatic portal vein, Hepatic stellate cell

28

Fatty livers occur in up to 20% of potential liver donors and increase cellular injury during the ischemia/reperfusion phase, so any intervention that could enable a better outcome of grafts for liver transplantation would be very useful. The effect of melatonin on liver ischemia/reperfusion injury in a rat model of obesity and hepatic steatosis has been investigated. Forty fa/fa Zucker rats were divided in 4 groups. 3 groups were subjected to 35min of warm hepatic ischemia and 36h of reperfusion. One experimental group remained untreated and two were given 10mg/kg melatonin intraperitoneally or orally. Another group was sham-operated. Plasma ALT, AST and hepatic content of ATP, MDA, hydroxyalkenals, NOx metabolites, antioxidant enzyme activity, caspase-9 and DNA fragmentation were determined in the liver. The expression of iNOS, eNOS, Bcl2, Bax, Bad and AIF were determined by RT-PCR. Melatonin was effective at decreasing liver injury by both ways as assessed by liver transaminases, markers of apoptosis, of oxidative stress and improved liver ATP content. Melatonin administration decreased the activities or levels of most of the parameters measured in a beneficial way, and our study identified also some of the mechanisms of protection. We conclude that administration of melatonin improved liver function, as well as markers of pro/antioxidant status and apoptosis following ischemia/reperfusion in obese rats with fatty liver. These data suggest that this substance could improve outcome in patients undergoing liver transplantation who receive a fatty liver implant and suggest the need of clinical trials with it in liver transplantation.

Concepts: Obesity, Liver, Liver function tests, Metabolic syndrome, Hepatology, Non-alcoholic fatty liver disease, Fatty liver, Steatosis

28

The present study investigated the acute, subchronic and genotoxicity of turmeric essential oil (TEO) from Curcuma longa L. Acute administration of TEO was done as single dose up to 5 g of TEO per kg body weight and subchronic toxicity study for thirteen weeks was done by daily oral administration of TEO at doses 0.1, 0.25 and 0.5 g/kg b.wt. in Wistar rats. There were no mortality, adverse clinical signs or changes in body weight; water and food consumption during acute as well as subchronic toxicity studies. Indicators of hepatic function such as aspartate aminotransferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) were unchanged in treated animals compared to untreated animals. Oral administration of TEO for 13 weeks did not alter total cholesterol, triglycerides, markers of renal function, serum electrolyte parameters and histopathology of tissues. TEO did not produce any mutagenicity to Salmonella typhimurium TA-98, TA-100, TA-102 and TA-1535 with or without metabolic activation. Administration of TEO to rats (1 g/kg b.wt) for 14 days did not produce any chromosome aberration or micronuclei in rat bone marrow cells and did not produce any DNA damage as seen by comet assay confirming the non toxicity of TEO.

Concepts: Bone, Mutation, Bone marrow, Liver function tests, Aspartate transaminase, Alanine transaminase, Mutagen, Curcuma

28

The efficacy of ursodeoxycholic acid (UDCA) on long-term outcome of primary biliary cirrhosis (PBC) has been less documented in Chinese cohort. We aimed to assess the therapeutic effect of UDCA on Chinese patients with PBC. In the present study, 67 patients with PBC were treated with UDCA (13-15 mg·kg(-1)·day(-1)) and followed up for 2 years to evaluate the changes of symptoms, laboratory values and histological features. As the results indicated, fatigue and pruritus were obviously improved by UDCA, particularly in patients with mild or moderate symptoms. The alkaline phosphatase and γ-glutamyl transpetidase levels significantly declined at year 2 comparing to baseline values, with the most profound effects achieved in patients at stage 2. The levels of alanine aminotransferase and aspartate aminotransferase significantly decreased whereas serum bilirubin and immunoglobulin M levels exhibited no significant change. Histological feature was stable in patients at stages 1-2 but still progressed in patients at stages 3-4. The biochemical response of patients at stage 2 was much better than that of patients at stages 3-4. These data suggest that, when treated in earlier stage, patients in long-term administration of UDCA can gain favorable results not only on symptoms and biochemical responses but also on histology. It is also indicated that later histological stage, bad biochemical response and severe symptom may be indicators of poor prognosis for UDCA therapy.

Concepts: Amino acid, Cirrhosis, Liver function tests, Hepatology, Bilirubin, Primary biliary cirrhosis, Primary sclerosing cholangitis, Ursodiol

28

Background: There are no studies on clinically significant transaminase elevation due to rotavirus gastroenteritis in the literature. Also, there are significant discrepancies among previous studies regarding the prevalence of increased serum transaminase levels in rotavirus infection. Methods: Patients investigated for rotavirus by stool antigen testing, who were followed between January 2005 and May 2012, were retrospectively enrolled in this study. Patients were divided into 2 groups according to their rotavirus results: rotavirus-positive acute gastroenteritis (RPAG) and rotavirus-negative acute gastroenteritis (RNAG) groups. Results: A total of 4317 children who presented with acute gastroenteritis were assessed. The study was completed with 642 patients who met the inclusion criteria. In the RPAG group (n = 272), elevated alanine aminotransferase (ALT) was found in 42 (15.4%) patients and elevated aspartate aminotransferase (AST) in 69 (25.4%), while in the RNAG group (n = 370), these numbers were 25 (6.8%) and 44 (11.9%), respectively. The elevated ALT and AST levels were found to be significantly higher in the RPAG group than in the RNAG group (both p < 0.001). The prevalence of elevated transaminase levels was found to be similar with respect to gastroenteritis severity score (p > 0.05). The high serum transaminase levels normalized uneventfully in all patients in the RPAG and RNAG groups during follow-up. Conclusions: In this study, our results clearly signify a liver influence in rotavirus infections. Therefore, rotavirus infections should be kept in mind when evaluating the aetiology of transaminase elevation in patients with acute gastroenteritis.

Concepts: Liver function tests, Aspartate transaminase, Alanine transaminase, Rotavirus, Diarrhea, Gastroenteritis, Oral rehydration therapy, Elevated transaminases

28

Most pomegranate (Punica granatum Linn., Punicaceae) fruit parts are known to possess enormous antioxidant activity. The present study was carried out to determine the phenolic and flavonoid contents of Derik pomegranate juice and determine its effect against carbon tetrachloride (CCl(4))-induced toxicity in rats. Animals were divided into four groups (n = 6): group I: control, group II: CCl(4) (1 ml/kg), group III: CCl(4) + pomegranate juice and group IV: CCl(4) + ursodeoxycholic acid (UDCA). Treatment duration was 4 weeks, and the dose of CCl(4) was administered once a week to groups II, III and IV during the experimental period. CCl(4)-treated rats caused a significant increase in serum enzyme levels, such as aspartate aminotransferase, alanine aminotransferase and total bilirubin, and decrease in albumin, when compared with control. Administration of CCl(4) along with pomegranate juice or UDCA significantly reduces these changes. Analysis of lipid peroxide (LPO) levels by thiobarbutiric acid reaction showed a significant increase in liver, kidney and brain tissues of CCl(4)-treated rats. However, both pomegranate juice and UDCA prevented the increase in LPO level. Histopathological reports also revealed that there is a regenerative activity in the liver and kidney cells. Derik pomegranate juice showed to be hepatoprotective against CCl(4)-induced hepatic injury. In conclusion, present study reveals a biological evidence that supports the use of pomegranate juice in the treatment of chemical-induced hepatotoxicity.

Concepts: Antioxidant, Liver, Liver function tests, Alanine transaminase, Pomegranate, Punica, Lythraceae, Punica protopunica

28

BACKGROUND: Liver function tests (LFTs) can be affected by many factors and the proposed effects of coffee on LFT require a comprehensive evaluation. The aim of this study was to elucidate whether drinking coffee, smoking, or drinking alcohol have independent effects on LFTs in Korean health-check examinees. METHODS: We used the responses of 500 health-check examinees, who had participated in a self-administered questionnaire survey about coffee, alcohol drinking, and smoking habits. RESULTS: Coffee consumption was closely related to male gender, high body mass index (BMI), alcohol drinking, and smoking. On univariable and multivariable analyses, drinking coffee lowered serum levels of total protein, albumin, and aspartate aminotransferases (AST). On multivariable analyses, smoking raised serum gamma-glutamyl transferase (GGT) level and decreased serum protein and albumin levels, while alcohol drinking raised GGT level after adjustment for age, gender, regular medication, BMI, coffee and alcohol drinking amounts, and smoking. CONCLUSIONS: Coffee consumption, smoking, and alcohol drinking affect the individual components of LFT in different ways, and the above 3 habits each have an impact on LFTs. Therefore, their effects on LFTs should be carefully interpreted, and further study on the mechanism of the effects is warranted.

Concepts: Liver, Liver function tests, Aspartate transaminase, Coffee, Body mass index, Alanine transaminase, Albumin, Affect

28

Purpose: To compare pure molecular diffusion, D, perfusion-related diffusion, D*, and perfusion fraction, f, determined from diffusion-weighted (DW) magnetic resonance (MR) imaging on the basis of the intravoxel incoherent motion (IVIM) theory in patients with type 2 diabetes with and without liver steatosis. Materials and Methods: This prospective study was approved by the appropriate ethics committee, and written informed consent was obtained from all patients. Between December 2009 and September 2011, 108 patients with type 2 diabetes (51 men, 57 women; mean age, 50 years) underwent 3.0-T single-voxel point-resolved proton MR spectroscopy of the liver (segment VII) to calculate the liver fat fraction from water (4.76 ppm) and methylene (1.33 ppm) peaks, corrected for T1 and T2 decay. Steatosis was defined as a liver fat fraction of at least 5.56%. DW imaging was performed by using a single-shot echo-planar sequence with 11 b values (0, 5, 15, 25, 35, 50, 100, 200, 400, 600, 800 sec/mm(2)). Liver D, D*, and f were measured and compared in patients with and patients without steatosis (Mann-Whitney test). Results: The mean liver fat fraction was 7.8% (standard deviation, 9%; range, 0.99%-45%). Forty patients had liver steatosis. D was significantly lower in steatotic compared with nonsteatotic livers (mean, 1.03 × 10(-3) mm(2)/sec ± 0.23 [standard deviation] vs 1.24 × 10(-3) mm(2)/sec ± 0.15, respectively; P < .0001), as was D* (mean, 72.2 × 10(-3) mm(2)/sec ± 61.4 vs 110.6 × 10(-3) mm(2)/sec ± 79; P = .0025). However, f was significantly higher in steatotic compared with nonsteatotic livers (mean, 33.8% ± 9.4 vs 26.9% ± 8.8; P = .0003). Conclusion: D is significantly decreased in steatosis. The reduction in D* reflects decreased liver parenchymal perfusion in steatosis. Therefore, steatosis can affect diffusion parameters obtained with IVIM. © RSNA, 2012.

Concepts: Informed consent, Obesity, Nuclear magnetic resonance, Magnetic resonance imaging, Liver function tests, Non-alcoholic fatty liver disease, Fatty liver, Steatosis