Serum GGT Research Articles

Replenishing glutathione counters ciprofloxacin-induced acute liver failure via possible gene modifying mechanism

Background: Acute liver failure (ALF) can be defined as rapid loss of liver functions even in the absence of pre-existing liver disorders. ALF is a medical emergency that necessitates hospitalization and, if not properly treated, a liver transplant may be the only cure. Herein, we studied the potential therapeutic effects of exogenous glutathione on drug-induced ALF. Materials: Thirty male Wistar albino rats were used in the present study. Rats were divided (10/group) into: control group (received only intra-peritoneal injection of distilled water), ciprofloxacin-treated group (received intra-peritoneal injection of 800 mg/kg/day ciprofloxacin for 15 consequent days with concomitant intra-peritoneal injection of distilled water), and ciprofloxacin + glutathione-treated group (received intra-peritoneal injection of 800 mg/kg/day ciprofloxacin for 15 consequent days with concomitant intra-peritoneal injection of 200 mg/kg/day glutathione). Measurement of serum ALT, AST, GGT and LDH enzymes activities were performed, and hepatic gene expression of CYP3A, GPx, GSR and Nrf2 mRNA was assessed. Results: Treatment with ciprofloxacin resulted in significant increase in ALT, AST, GGT and LDH enzymes activities when compared to the control group. Ciprofloxacin also induced significant down-regulation of CYP3A, GPx, GSR and Nrf2 mRNA gene expression when compared to the corresponding values in the control group. Glutathione administration significantly normalized ALT, AST, GGT and LDH enzymes activities and up-regulated CYP3A, GPx, GSR and Nrf2 mRNA gene expression. Conclusion: Glutathione could play potential therapeutic roles in the treatment of acute liver failure by preventing oxidative stress-induced disruption of hepatocyes cell membranes and alteration in cytochrome P450 and the antioxidant genes.

Bezafibrate therapy in primary biliary cholangitis refractory to ursodeoxycholic acid: a longitudinal study of paired liver biopsies at 5years of follow up.

Ursodeoxycholic acid (UDCA) is the first-line therapy for primary biliary cholangitis (PBC). However, nearly 40% of patients have an incomplete response to UDCA. The addition of bezafibrate has shown biochemical benefit in this group of patients. To evaluate the long-term effects of UDCA in combination with bezafibrate on histological outcomes in patients with UDCA-refractory PBC. Fifty-nine patients refractory to UDCA were included. Clinical parameters were monitored and paired liver biopsy (PLB) was performed after 5years of follow-up. Of the total cohort, 49 subjects were analysed and 31had PLB at 5years. Values for serum ALP, AST, ALT and GGT significantly improved with UDCA-bezafibrate. This beneficial effect was observed at 12months where 86% achieved ALP at normal levels. Analyses of PLB showed a significant decrease in liver damage as reflected by Ludwig (baseline 2.29±1.2, to 1.84±1 at year 5, P=0.0242) and Ishak (baseline 6.19±2.2 to 4.77±2.2 at year 5, P=0.0008) scores. Overall, regression of fibrosis was attained in 48% of patients. Furthermore, we observed a significant reduction in the proportion with cirrhosis from 19% at baseline to 3% at 5years (P<0.001). These beneficial effects were associated with better predictive risk scores using the GLOBE and UK-PBC prognosis models. Adding bezafibrate to UDCA in patients with UDCA-refractory PBC showed a significant decrease in fibrosis and inflammatory histological scores at 5years. These beneficial effects warrant further evaluation in long-term cohort studies and controlled trials.

The protective effects and mechanisms of modified Lvdou Gancao decoction on acute alcohol intoxication in mice

Ethnopharmacological relevanceAcute alcohol intoxication (AAI) is a ubiquitous emergency worldwide, whereas the searching for both effective and safe drugs is still a task to be completed. Modified Lvdou Gancao decoction (MLG), a traditional Chinese medicine decoction, has been confirmed to be valid to alcohol-induced symptoms and hepatotoxicity clinically, whereas its protective mechanisms have not been determined. Materials and methodsAAI mice model was established by alcohol gavage (13.25 mL/kg) and MLG (5, 10, 20 g/kg BW) was administered to mice 2 h before and 30 min after the alcohol exposure. Assay kits for alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamine transferase (GGT), total superoxide dismutase (T-SOD), malondialdehyde (MDA), nitric oxide (NO), and glutathione peroxidase (GSH-Px), as well as histopathology were used to explore the effects of MLG on acute alcohol-induced intoxication and hepatotoxicity. Mechanisms of MLG on oxidative stress and inflammatory were evaluated with RT-qPCR and Western Blot. ResultsMLG remarkably decreased the drunkenness rate, prolonged the tolerance time and shortened the sober-up time of AAI mice. After acute alcohol exposure, MLG treatment induced significant increment of ADH, ALDH, T-SOD and GSH-Px activities in liver, while serum ALT, AST, GGT and NO levels as well as hepatic MDA activity were reduced, in a dose-dependent manner. In contrast to the model group, the mRNA expression of TNFα, IL-1β and NF-κB in the MLG treated groups had a downward trend while the Nrf-2 showed an upward trend simultaneously. Furthermore, the protein levels of p65, p-p65, p-IκBα in the MLG treated groups were considerably diminished, with HO-1 and Nrf2 elevated. To sum up, our results suggested that MLG could efficaciously ameliorate AAI via accelerating the metabolism of alcohol, alleviating acute hepatotoxicity, and weakening the oxidative stress coupled with inflammation response, which might be attributed to the inhibition of the NF-κB signaling pathway and the activation of the Nrf2/HO-1 signaling pathway. ConclusionsTaken together, our present study verified the protective effect and mechanisms of MLG to AAI mice, and we further conclude that MLG may be a potent and reliable candidate for the prevention and treatment of AAI.

Association between FTO (rs17817449) genetic variant, gamma-glutamyl transferase, and hypertension in Slovak midlife women.

This cross-sectional study investigates associations between the FTO rs 17817449 genetic variant, liver enzymes, and hypertension in Slovak midlife women. We assessed 576 Slovak women aged 39 to 65 years. The women were interviewed and examined during their medical examination at local Health Centers and then divided into subgroups according to their blood pressure status; 255 women with hypertension and 321 normotensive. The FTO genetic variant was detected by polymerase chain reaction-restriction fragment length polymorphism. Resultant data was analyzed by linear regression analysis and general linear models to adjust for risk factors associated with gamma-glutamyl transferase levels (GGT), including waist to hip ratio (WHR) and uric acid (UA). A significant association between the FTO variant and GGT levels was observed in the hypertensive group after control for confounding covariates, including WHR and UA (p=.004). The predicted GGT level for GT/TT hypertensive carriers is 0.158 μkat/L higher than for GG carriers. Moreover, the two-way analysis of covariance revealed significant interaction between FTO effects and hypertension on logGGT levels (p=.042). Finally, hypertensive women with the T-allele had the highest estimated marginal mean value of logGGT at -0.39 μkat/L while the GG-genotype in both hypertensive and normotensive women had the lowest value at -0.54 μkat/L. This study suggests that the FTO (rs17817449) variant is associated with higher serum GGT levels in hypertensive midlife women.

Expression Status and Prognostic Significance of Gamma-Glutamyl Transpeptidase Family Genes in Hepatocellular Carcinoma.

PurposeGamma-glutamyl transpeptidase (GGT) family genes play crucial roles in the formation and progression of several solid tumors. However, the expression patterns and the prognostic significance of GGT members in hepatocellular carcinoma (HCC) remain unknown. This study was designed to determine the expression profiles of GGT family members in HCC and validate the prognostic value of serum GGT protein in patients with HCC.MethodWe comprehensively searched public resources based on the LIHC dataset to determine the expression patterns, prognostic significance, DNA methylation status, immune infiltration, and biological pathways of GGT family genes in HCC. Subsequently, we validated the prognostic value of serum GGT protein in 85 patients with early-stage HCC subjected to curative hepatectomy from the Renmin Hospital of Wuhan University.ResultsExcept for GGT1, other GGT family members (GGT5, GGT6, and GGT7) were found to be differentially expressed in primary HCC samples (N = 371) and normal control tissues (N = 50). Furthermore, a positive relationship was not only observed between GGT1 and GGT5 (Spearman coefficient: 0.24, P = 5.143 × 10−6) but also between GGT5 and GGT6 (Spearman coefficient: 0.38, P = 1.24 × 10−13). The expression of GGT1, GGT5, and GGT7 was correlated with overall survival (OS), and GGT7 was associated with disease-free survival (DFS) in patients with HCC. Negative associations between DNA methylation and expression of mRNA were observed for GGT1 (Spearman coefficient: −0.38, P = 6.24e-14), GGT6 (Spearman coefficient: −0.29, P = 1.23e-8), and GGT7 (Spearman coefficient: −0.34, P=6.7e-11). GGT family genes were well correlated with the infiltration levels of immune cells in HCC, especially CD4+ T cells, macrophages, and dendritic cells. Finally, when validated with clinical data from the Renmin cohort, a high expression of serum GGT protein was identified as a strong prognostic element of unfavorable OS (HR = 3.114, P = 0.025), but not of DFS (HR = 1.198, P = 0.05) in patients with HCC subjected to curative hepatectomy.ConclusionTo our knowledge, this is the first comprehensive analysis of the expression patterns and clinical value of GGT family genes in patients with HCC. Our study laid the foundation for the clinical application of the GGT protein in the survival assessment of patients with HCC.

Analysis of relationship of hormonal, hematological and biochemical parameters in Indian alcoholics with severity of alcohol dependence

BackgroundAlcohol dependence syndrome (ADS) is a major problem in India. ADS is known to be a systemic disorder involving almost all organ-systems. The evaluation of ADS patients’ needs successive assessment of severity of clinical condition. In this study, we attempted to explore Severity of Alcohol Dependence Questionnaire (SADQ-C) as a severity measure by studying its association with laboratory parameters. MethodsDuring the two months study period 155 diagnosed ADS male patients who had been admitted to the Psychiatric Ward of two zonal level hospitals were enrolled for the study. The participants were examined by the Psychiatrist and the severity of alcoholism ascertained by the SADQ-C scoring. Based on SADQ-C scoring they were divided into three groups: severe alcohol dependence, moderate dependence and mild physical dependence. The patients’ blood samples were collected and tested. ResultsIn our study, morning and evening level of serum cortisol showed positive correlation with increasing SADQ-C scoring. The differences in morning and evening cortisol level also augmented with increasing severity score (r=0.257; p=0.001). Hemoglobin, mean corpuscular volume (MCV) and serum level of LH, FSH and testosterone levels were not shown any statistically significant alterations amongst the studied groups. Serum LH, total bilirubin, direct bilirubin, AST, ALT and GGT level showed positive correlation with SADQ-C scoring but AST/ALT ratio showed negative correlation. ConclusionThis study elaborated relationship between SADQ-C scoring and laboratory parameters in Indian male ADS patients. It highlighted the requirement of incorporation of serum cortisol along with presently evaluated laboratory parameters for ADS severity evaluation.

Efficacy of Sorafenib Combined with Interventional Therapy on Primary Liver Cancer Patients and Its Effect on Serum AFP, VEGF, and GGT

Objective To explore the efficacy of sorafenib combined with interventional therapy on primary liver cancer (PLC) patients and its effect on serum AFP, VEGF, and GGT. Methods 120 PLC patients admitted to our hospital from January 2016 to January 2020 were selected as the research object and divided into group A and group B according to the admission order, with 60 cases each. Interventional therapy was performed to both groups, and sorafenib was given to group A additionally to compare their treatment effect, survival, adverse reaction rate (ARR), and serum AFP, VEGF, and GGT levels. Results After treatment, group A obtained significantly higher objective remission rate (ORR) and disease control rate (DCR) (p < 0.05), higher one-year survival rate and two-year survival rate (p < 0.05), lower ARR of skin reactions, gastrointestinal reactions, hepatorenal reactions, and hyperbilirubinemia (p < 0.05), and lower serum AFP, VEGF, and GGT levels (p < 0.001). Conclusion The combination of sorafenib and interventional therapy can inhibit the growth and migration of PLC, improve the immune function, prolong the survival period of patients, and lower ARR, so it should be promoted in practice.

Peripheral Arrangement of Steatosis Microvacuoles in Wilson’s Disease

A 17-year-old girl was referred for jaundice and severe liver failure (international normalized ratio, 2.4; Factor V 19%, and total bilirubin level, 85 μmol/L). Transaminase and serum GGT levels were slightly elevated. There was hemolytic anemia with a negative Coombs test and thrombocytopenia. The liver was dysmorphic with splenomegaly. There was no viral hepatitis; the IgG level reached 21 g/L without autoantibodies. Her urinary copper level was 1779 μg/24 hours (N < 0.6), ceruloplasmin level was 0.12 g/L (N > 0.2), and a high exchangeable copper to total copper ratio (23.4%; N < 8.0) and hepatic copper level (844 μg/g) supported the diagnosis of Wilson's disease.

Hepatoprotective and Curative Activities of Daphne Gnidium L. Aqueous Extract Against CCl4-Induced Liver Injury in Rats

Background: The liver is one of the largest organs of the human body and the main site for intense metabolism and excretion. Liver injury or dysfunction is recognized as a serious worldwide health problem. Daphne gnidium L., a medicinal plant widely distributed in Algeria and used by populations in traditional medicine to treat hepatitis and other diseases. Objective: Protective and curative effects of aqueous extract of Daphne gnidium L. leaves were investigated against Carbon Tetrachloride (CCl4) induced hepatic damage in rats (Wistar Albino). Method: This study was conducted on 32 Albino rats, which were divided into four groups; the first served as control. Group II animals were treated intraperitoneally with CCl4solution (3ml/ kg). Group III animals were treated intraperitoneally with CCl4solutions (3ml/kg) on the first day, and given aqueous Daphne extract orally at a dose level of (300 mg/kg) daily for 7 days (curative activity test). Animals of group IV were orally administered aqueous Daphne extract at a dose level of (300 mg/kg) daily, and on the seventh day treated intraperitoneally with CCl4solution (3ml/ kg) 3 hours after the latest extract administration (preventive activity test). Results: Our results show that CCl4significantly increases the relative liver weight, serum values of ALT, AST, ALP, GGT, and Total bilirubin, as well as the hepatic rate of oxidative stress parameters; MDA and CAT activities, and significantly decreases hepatic GSH levels compared to the control group. These results were confirmed by liver lesions observed in histological analyses. Pretreatment and curative treatment of dose 300 mg/kg of aqueous Daphne gnidium L. extract significantly reduced relative weight, serum levels of ALT, AST, ALP, GGT and Total bilirubin liver rate, CAT activity, and increases GSH level. In addition, normal liver architecture has been restored. Conclusion: The present study demonstrates the hepatoprotective and curative effects of aqueous extract Daphne gnidium leaves against CCl4-induced liver injury in rats by improving the antioxidant status in tissues (liver) and ameliorating the harmful effects induced by CCl4

Keratin 7 expression in hepatic cholestatic diseases

We evaluated keratin 7 (K7) hepatocellular expression in 92 patients with common types of acute and chronic cholestatic diseases caused by bile duct obstruction/destruction or parenchymal lesions [acute hepatitis (n=20), mixed/pure cholestasis (n=16), primary biliary cholangitis-PBC (n=35), primary sclerosing cholangitis-PSC (n=10), vanishing bile duct syndrome (n=3), complete large bile duct obstruction due to space-occupying lesions (n=8)]. K7 immunohistochemical hepatocellular expression and ductular reaction (DR) were semi-quantitatively assessed. Results were correlated with liver enzyme serum levels, cholestasis type, histological features, hepatocellular Ki67 labelling index (LI) and HepPar1 expression. Hepatocellular K7 expression was detected in 87% (81/92) cases and in all cholestatic disease types with lowest incidence in pure/mixed cholestasis and highest in incomplete bile duct obstruction (iBDO), reaching 100% in PSC. K7-positive hepatocytes had low Ki67 LI (0-5%) retaining HepPar1 expression, irrespective of disease type. PSC cases had high K7 hepatocellular expression even with intact bile ducts, a feature that may aid differential diagnosis of cholestatic syndromes. K7 hepatocellular expression significantly correlated with cholestasis type, bile duct loss and fibrosis stage. It was higher in milder acute cholestatic hepatitis showing inverse correlation with hepatocyte proliferation and serum transaminase levels. In iBDO, younger age independently correlated with high K7 expression, while serum GGT levels showed a nearly significant correlation. Correlation with DR findings implied that K7-positive hepatocytes may result through metaplasia. In conclusion, K7 hepatocellular expression is a sensitive though non-specific marker of cholestasis. It may represent a cytoprotective reaction of resting hepatocytes in cholestasis of longer duration especially in younger patients.

Zanthoxylum zanthoxyloides Alkaloidal Extract Improves CCl4-Induced Hepatocellular Carcinoma-Like Phenotypes in Rats.

Background Despite the enrollment of new small molecules such as Sorafenib for the treatment of hepatocellular carcinoma (HCC), HCC still remains a significant contributor to cancer-related mortality and morbidity globally. Zanthoxylum zanthoxyloides is long suspected of possessing anticancer bioactive compounds that may hold the prospect of adjunctive therapy against inflammation-related cancers such as HCC. Objective This study assessed the effects of an alkaloidal extract of the leaves of Zanthoxylum zanthoxyloides on CCl4/olive oil (1 : 1 v/v)-induced HCC-like phenotypes in rats. Materials and Methods Zanthoxylum zanthoxyloides alkaloidal extract (ZZAE) was prepared using Soxhlet and liquid-liquid extraction methods. Subsequently, ZZAE was characterized phytochemically. In the curative method, experimental HCC was established in adult (8–10 weeks old) male Sprague-Dawley rats weighing 150–300 g by twice-daily administration of CCl4/olive oil (1 : 1 v/v) (2 mL/kg ip). After confirmation of experimental HCC in rats, the rats were randomly reassigned into seven (7) groups of seven (7) rats each and treated daily for 12 weeks as follows: control (normal saline, 5 ml/kg po), model (CCl4, 5 ml/kg, ip), ZZAE (50, 100, and 200 mg/kg po), carvedilol (6.25 mg/kg po), and 20% Tween20 (1 mL/rat, po). To assess whether ZZAE has a prophylactic (preventive) effect, rats were first treated with ZZAE and later exposed to CCl4 reconstituted in olive oil. Results ZZAE (100 and 200 mg/kg) and carvedilol decreased tumor incidence compared to that of control. Compared to control, ZZAE (100 and 200 mg/kg) significantly (P < 0.05) improved serum GGT. Compared to control, ZZAE improved hepatohistological distortions induced by CCl4/olive oil and also improved liver/body weight ratio. Compared to water, ZZAE arrested mitosis in the Allium cepa assay. Conclusion ZZAE ameliorated CCl4/olive oil-induced HCC-like phenotype in rats and demonstrated general hepatoprotective effects by improving liver and kidney function markers. This finding rationalizes the need for further studies on ZZAE as a potential source of bioactive anti-HCC compounds.

A Study on the Serum γ-Glutamyltranspeptidase and Plasma Osteopontin in Alcoholic Liver Disease.

Background Alcoholic liver disease (ALD) is a major source of alcohol-related morbidity and mortality. Heavy drinkers and alcoholics may progress from fatty liver to alcoholic hepatitis to cirrhosis. The enzyme γ-glutamyltranspeptidase (GGT) is a membrane-bound glycoprotein which catalyzes the transfer of the γ-glutamyl group from γ-glutamyl peptides to other peptides, amino acids, and water. Serum GGT activity mainly attributed to hepatobiliary system and thus is an important marker of ALD. Hence the present study is conducted to estimate and correlate the levels of GGT and osteopontin (OPN) in ALD. Aims and Objectives The objective of this study is to estimate and correlate the levels of GGT and OPN in ALD. Materials and Methods Sixty clinically diagnosed cases of ALD and sixty age- and gender-matched healthy controls were recruited for the study. Blood samples were collected from them and serum aspartate aminotransferase, serum alanine transaminases (ALTs), serum ALP levels, and plasma OPN levels were measured. Estimation of serum aspartate transaminases (AST), ALTs, and alkaline phosphatase (ALP) was assayed by standard photometric methods in autoanalyzer ERBA-XL (EM-200) using commercially available kits. OPN was estimated by using commercial kit based on enzyme-linked immunosorbent assay. Results The parameters of the liver function tests such as AST, ALT, and ALP were significantly increased in patients with ALD ( p < 0.001) when compared with the healthy control subjects. In the present study, significantly increased levels of γ-glutamyl transferases and OPN were found in patients with ALD ( p < 0.001) when compared with the control subjects. OPN showed significant positive correlations with AST ( r = 0.76, p < 0.001), ALT ( r = 0.64, p < 0.001), ALP ( r = 0.68, p < 0.001), and GGT ( r = 0.61, p < 0.001). Conclusion The present study focuses on the role of GGT and OPN that are sensitive indicators of liver cell injury and are most helpful in recognizing hepatocellular diseases such as ALD, hepatitis, and liver cirrhosis. Hence, the pattern of the GGT and OPN levels elevation can be helpful diagnostically.

The estimation of serum gamma glutamyl transferase in fatty liver disease

Background: Fatty liver seems to be common problem among the young and middle aged population. It includes a spectrum of liver disease from simple fatty liver to hepatic steatosis to cirrhosis and hepatocellular carcinoma. Fatty liver disease comprises both alcoholic fatty liver disease to non alcoholic fatty liver disease. Early detection of fatty liver disease helps to prevent these major events of disease progression. The serum gamma glutamyl transferase level rise early in the spectrum of fatty liver disease and returns back to normal in most of the cases. So estimation of the serum gamma glutamyl transferase in fatty liver disease serves as an non invasive biomarker in fatty liver disease. Aims and Objectives: To evaluate the serum GGT levels in patients with fatty liver and to show that it can be used as a non invasive diagnostic biomarker for the diagnosis of fatty liver disease. Materials and Methods: The study was a case control study which was done in100 patients. Of the total 100 cases 50 were categorized as case group with ultrasound abdomen finding of fatty liver and the remaining 50 are control group with normal ultrasound abdomen reports. The investigations like, serum gamma glutamyl transferase, liver function test, renal function test, serum random blood sugar, fasting lipid profile, HIV, HbsAg were done with special importance given to serum GGT levels. These parameters between the case and control group were studied based on pearson correlation test and student t-test. Results: Comparison of GGT values between case and control group, which shows serum GGT level of 69.38 ± 16(IU/L) cases and21.34 ± 5.29(IU/L) controls. The mean serum TGL level was 300 ± 39(IU/L), serum LDL level was 138.5 ± 27(IU/L) in the case (fatty liver) group and the control (normal) group TGL level was 230 ± 35.5(IU/L), LDL level was 138.5 ± 27(IU/L) which was statistically significant and p value was

Effects of H3 and H4 histones acetylation and bindings of CREB binding protein and p300 at the promoter on hepatic expression of gamma-glutamyltransferase gene in a streptozotocin-induced moderate hypoinsulinemic rat model.

Gamma-glutamyltransferase (GGT), a marker of liver disease, has been shown to be associated with increased risk of diabetes and relative insulin secretion deficiency. However, the mechanism of hepatic Ggt regulation has not been explored fully. In this study, we made a concerted effort to understand the mechanism by investigating the effects of acetylation of histones H3 and H4, and bindings of histone acetyltransferases, CREB binding protein (CBP) and p300, at the Ggt promoter on the regulation of the expression of Ggt gene in the livers of streptozotocin (STZ)-induced moderate hypoinsulinemia rat model. The rats treated with STZ showed remarkably higher serum GGT level and hepatic Ggt/GGT expression than the untreated control rats. Furthermore, the acetylation of histones H3 and H4, and the binding of CBP not p300 at the Ggt promoter regions were significantly higher in the livers of STZ rats than those of the control rats. These results suggest that an enhanced hepatic expression of Ggt is associated with increased acetylation of histones H3 and H4 and CBP binding at the Ggt promoter in STZ-induced moderate hypoinsulinemic rats.

AKP and GGT level can provide an early prediction of first-line treatment efficacy in colorectal cancer patients with hepatic metastases.

Aim: It is important to early evaluate or predict the efficacy to avoid ineffective treatment for most colorectal cancer (CRC) patients with liver metastases. Patients & methods: The medical records of 440 patients with histologically confirmed primary CRC admitted to the Fudan University Shanghai Cancer Center were reviewed. Results: High baseline serum alkaline phosphatase (AKP) and γ-glutamyl transferase (GGT) is associated with worse overall survival. In patients with a high serum AKP and GGT a decreased percentage had high objective response rate and better progression-free survival. Conclusion: Measuring the changes of serum AKP or GGT in CRC patients with hepatic metastases before and after the first cycle of treatment is a convenient, fast and economical way to early predict antitumor treatment efficacy.

Enhanced Susceptibility to Breast Cancer in Korean Women With Elevated Serum Gamma-Glutamyltransferase Levels: A Nationwide Population-Based Cohort Study.

BackgroundThe incidence of breast cancer has been gradually increasing in Korea. Recently, the elevated level of serum gamma-glutamyltransferase (GGT) has emerged to be associated with the development and progression of some malignancies. This study aimed to determine the effect of serum GGT levels on the risk of developing breast cancer in Korean women.MethodsWe used National Health Insurance Service Health Checkup data to examine the association between serum GGT levels and breast cancer development in Korean women. Women aged 40 years or older who participated in the Korean National Health Screening Examination between January 2009 and December 2009 and who did not develop any cancer within 1-year post examination were included in this analysis (n = 3,109,506). Cox proportional hazard regression analysis was conducted to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsOverall, an elevated serum GGT level was associated with the increased risk of developing breast cancer; compared to the Q1 group, the Q4 group showed a significantly increased breast cancer risk (HR: 1.120,95% CI: 1.08–1.162). Such a relationship was stronger in post-menopausal women than pre-menopausal women (HR: 1.173, 95% CI: 1.107–1.243; HR: 1.070, 95% CI:1.019–1.124). Women with a high GGT level (Q4) were also at an increased risk of developing carcinoma in situ (CIS) (HR: 1.114, 95% CI: 1.04–1.192). In post-menopausal women, the Q4 group also exhibited higher CIS risk (HR: 1.266, 95% CI: 1.132–1.416). However, no significant difference in the risk of developing CIS was observed between the Q1 and Q4 groups in pre-menopausal women. Further analysis revealed that obese, post-menopausal women with a high GGT level (Q4) were associated with an increased risk of developing breast cancer (HR: 1.214, 95% CI: 1.125–1.31) and CIS (HR: 1.348, 95% CI: 1.159–1.569).ConclusionsOur study results demonstrate that increased serum GGT level is a risk factor for developing breast cancer. The post-menopausal women group with obesity and elevated serum GGT level showed the highest incidence of breast cancer. Thus, serum GGT concentration could be a novel and potential risk factor for breast cancer. Further validation in different ethnic groups would be warranted.

Hepatocyte-derived canine familiaris-microRNAs as serum biomarkers of hepatic steatosis or fibrosis as implicated in the pathogenesis of canine cholecystolithiasis.

Hepatic cholesterol accumulation in small breed dogs is a leading risk factor for hepatic fatty changes, gallbladder hypomotility, and cholelith development, which, if not discovered early, could lead to life-threatening choledocholithiasis and acute pancreatitis. This study proposed to assess the use of hepatocyte-derived canine familiaris (cfa)-microRNAs (miRNA-122, -34a, and -21) as new diagnostic serum biomarkers of liver steatosis or fibrosis, for which both processes have been implicated in canine cholecystolithiasis. Forty client-owned dogs diagnosed with cholecystolithiasis and hepatic steatosis (C+HS) or fibrosis (C+HF) based on ultrasonographic, biochemical, and histopathologic findings, and 20 healthy dogs used as controls were included in the study. Serum cfa-miRNA expression was determined using a real-time polymerase chain reaction assay. Serum cfa-miRNA-122 and -34a expression was significantly upregulated in the C+HS (P<.001) and C+HF (P<.01) groups compared with the control group and showed a positive correlation with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total cholesterol (TC), and triglycerides (TG) levels in the C+HS group. Cfa-miRNA-122 and -34a expression discriminated the diseased groups from the control group betterthan traditional serum-derived liver biomarkers, as evidenced by areas under the receiver operating characteristic (AUC-ROC) curve of 0.99 and 0.97 for cfa-miRNA-122 expression in the C+HS and C+HF groups, and 1.0 and 0.96 for cfa-miRNA-34a in the C+HS and C+HF groups, respectively. Cfa-miRNA-21 expression was upregulated only in the C+HF group compared with the C+HS (P<.01) and control (P<.001) groups and showed a positive correlation with serum ALT, AST, TBIL, ALP, and GGT and negative correlation with serum TC and TG levels. Cfa-miRNA-21 expression could also differentiate the C+HF group from the control and C+HS groups with a diagnostic performance superior to that of the conventional serum biochemical variables as evidenced by AUCs of 1.0 and 0.98, respectively. Serum cfa-miRNA-122, -34a, and -21 expression was significantly upregulated in dogs with cholecystolithiasis with hepatic steatosis or fibrosis compared with control dogs. These miRNAs could serve as novel biomarkers for hepatic steatosis or fibrosis, which have been implicated in the pathogenesis of cholecystolithiasis.

Preoperative Serum Gamma-Glutamyltransferase as a Prognostic Biomarker in Patients Undergoing Radical Cystectomy for Bladder Cancer.

BackgroundSerum gamma-glutamyltransferase (GGT) has been reported to be correlated with survival in a variety of malignancies. However, its effect on patients with bladder cancer (BC) treated by radical cystectomy has never been evaluated.Patients and MethodsWe retrospectively evaluated 263 patients who underwent radical surgery in our center. Baseline features, hematologic variables, and follow-up data were obtained. The endpoints included overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). The relationship between GGT and survival were evaluated.ResultsThe median follow-up period for all patients was 34.7 (22.9-45.9) months. At the last follow-up, 67 patients died, 51 patients died of cancer, 92 patients experienced disease recurrence. Patients with an elevated serum GGT had a higher rate of pT3-T4 tumors. Patients with a higher preoperative serum GGT had a lower rate of OS, CSS and DFS (P < 0.001 for all). Multivariate analysis identified that preoperative serum GGT was independent predictor of OS (HR: 3.027, 95% CI: 1.716-5.338; P < 0.001), CSS (HR: 2.115, 95% CI: 1.093-4.090; P = 0.026), DFS (HR: 2.584, 95% CI: 1.569-4.255; P < 0.001). Age, diabetes history, pathologic T stage, and lymph node status also were independent predictors of prognosis for BC patients.ConclusionsOur results indicated that preoperative serum GGT was an independent prognosis predictor for survival of BC patients after radical cystectomy, and can be included in the prognostic models.

Association Between Sex-Specific Serum Gamma-Glutamyltransferase and Incidence of Hypertension in a Chinese Population Without Metabolic Syndrome: A Prospective Observational Study.

Background: Higher serum gamma-glutamyltransferase (GGT) is associated with high risk of hypertension. We aimed to examine the association between sex-specific serum GGT levels and incident of hypertension in a Chinese population without metabolic syndrome.Methods: Participants who were free of hypertension and metabolic syndrome from the First Affiliated Hospital of Wenzhou Medical University between 2009 and 2014 were included. Participants were grouped into sex-specific quartiles of GGT levels (Q1–Q4) defined as: ≤19, 20–26, 27–38, and ≥39 U/L for male; ≤12, 13–15, 16–19, and ≥20 U/L for female. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incidence of hypertension according to sex-specific quartiles of GGT levels. Kaplan–Meier analysis and interaction analysis were conducted.Results: Among 38,806 participants included (average age 36.0 years, 54.0% men), 4,505 of them developed hypertension. In the overall study population, using Q1 as the reference group, participants in Q2, Q3, and Q4 showed a higher risk of developing hypertension, with HRs (95% CIs) of 1.126 (1.029–1.232), 1.187 (1.083–1.302), and 1.300 (1.182–1.431), respectively (P < 0.001), after adjusting for known confounders. Sex-specific analysis showed that the adjusted HRs for participants in Q4 (reference: Q1) were greater in females [1.321 (1.100–1.586, P < 0.001)] than in males [1.268 (1.133–1.420, P < 0.001)] (P for interaction = 0.047). Moreover, interaction analysis showed that this association was consistently observed when the participants were stratified by age, body mass index, and fatty liver status.Conclusion: Among Chinese adults without metabolic syndrome, serum GGT level was positively associated with incidence of hypertension, and the association was stronger in females than in males.

TIME COURSE STUDY OF COMBINED N-ACETYL-P-AMINOPHENOL AND DICLOPHENAC INDUCED-HEPATOTOXICITY AND OXIDATIVE STRESS IN WISTAR RATS

The abuse of combined acetaminophen or N-acetyl-p-aminophenol (APAP) and diclofenac (DIC) due to their analgesics, anti-inflammatory and antipyretic properties is a predominant cause of hepatotoxicity and oxidative stress. This study investigated the time-course effects of APAP, DIC and their combination on biomarkers of hepatic function and oxidative stress in rats. Forty male Wistar rats were randomly divided into four groups of 10 animals each as follows; control (distilled water), APAP only, DIC only and APAP + DIC for 4 weeks. Indices of liver damage (serum ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; GGT, gamma-glutamyl transferase and bilirubin) were measured. Oxidative stress biomarkers (MDA, malondialdehyde; NO, nitric oxide; CAT, Catalase activity; SOD, superoxide dismutase activity; GSH content, reduced glutathione), GR, glutathione reductase, and GST, glutathione-S-transferase) were also determined using spectrophotometric methods. Statistical analysis was done using one-way ANOVA with p &lt; 0.05 considered significant. Acetaminophen and diclofenac caused marked liver damage as noted by time-dependent significant (p &lt; 0.05) increased activities of serum ALT, AST, ALP, GGT, and bilirubin levels as well as significant (p &lt; 0.05) increase in hepatic MDA and NO levels as compared to the control group. Hepatic GSH content, SOD, CAT, GPx, GST and GR activities were decreased significantly (p &lt; 0.05) in all acetaminophen and diclofenac-treated groups compared to normal control in a time-dependent manner. These findings suggest that prolonged administration of diclofenac, acetaminophen or their combination may induce hepatotoxicity, oxidative stress and alteration of hepatic antioxidant status in a time-dependent manner.