Elevated Serum Alanine Aminotransferase Levels Research Articles

Serum Lactate, AST, ALT in Male Autistic Children in Bangladesh

Background: Mitochondrial dysfunction has been found associated with abnormal brain bioenergetics resulting in autistic spectrum disorder (ASD)Objective: To assess serum lactate, AST, ALT in order to observe the mitochondrial dysfunction in male children with autistic spectrum disorder.Method: This case-control study was conducted in the Department of Physiology of Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka from January, 2013 to December, 2013. Total 100 male children with age range 3-8 years were randomly selected, among which 50 were normal children and 50 were diagnosed autistic children. Autistic children were enrolled from the Parent’s Forum for autistic children in Dhaka and the control subjects were selected from normal school. Serum lactate, Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) were estimated in all children by standard laboratory method. Independent sample‘t’ test was used for statistical analysis.Results: All these biochemical parameter were found significantly higher (p<0.001) in ASD children. In addition, elevated levels of serum lactate, AST and ALT were found in 94%, 46%, and 30% of autistic children respectively.Conclusion: From the result of this study it can be concluded that mitochondrial dysfunction may occur in children with autistic spectrum disorder.Bangladesh Soc Physiol. 2015, December; 10(2): 56-60

Free fatty acids, not triglycerides, are associated with non-alcoholic liver injury progression in high fat diet induced obese rats.

BackgroundThe incidence of non-alcoholic fatty liver disease (NAFLD), commonly associated with obesity and metabolic syndrome, is increasing worldwide. However, the specific mechanisms that mediate the progression from simple steatosis to non-alcoholic steatohepatitis remain largely unclear. This study aimed to investigate the timedependent changes of triglyceride (TG) and free fatty acid (FFA) levels in the blood and liver over 24 weeks in high-fat diet-induced obese rats with NAFLD and to clarify the role of high FFA levels in the progression of liver injury.MethodsMale Wistar rats were randomly divided into three groups (n = 30 per group): the Control group, fed standard chow; the High-fat diet (HFD) group, fed high-fat chow; and the Acipimox group, fed an HFD plus acipimox (100 mg/kg/d, ig) for 8, 16 and 24 weeks. After treatment, blood and liver samples were collected for biochemical analyses, western blotting analysis and a histopathological study.ResultsThe visceral fat/weight and liver/body weight ratios were higher in both the HFD and Acipimox groups than in the Control group. The TG and FFA concentrations in blood and liver were increased in the HFD group and associated with elevated serum alanine aminotransferase (ALT) and liver malondialdehyde (MDA) levels and macro/microvesicular steatosis on hepatic fragments. Although the TG levels in the liver were similar between the HFD and Acipimox groups (p > 0.05), the FFA concentrations in the blood and liver were much lower in the latter group (p < 0.05). The Acipimox group showed normal ALT and MDA levels as well as less severe hepatic histological changes than did the HFD group (NAFLD activity score: 2.14 ± 0.14, 2.43 ± 0.20 and 2.63 ± 0.26 at 8, 16 and 24 weeks, respectively; p < 0.05 versus the HFD group at 24 weeks). The diacylglycerol acyltransferase 2 (DGAT2) protein levels were similar between the HFD and Acipimox groups (p > 0.05), but the protein expression level of carnitine palmitoyltransferase 1a (CPT-1a) was higher in the Acipimox group.ConclusionsLiver TG accumulation does not cause cellular injury in the liver; rather, FFAs or their metabolites are responsible for liver injury via increased oxidative stress. It is suggested that the therapeutic efforts to prevent non-alcoholic liver injury progression should be focused on reducing the burden of fatty acids transported to the liver or those being synthesized in the liver.

Metabolic Syndrome and Serum Liver Enzymes in the General Chinese Population.

Background: The aim of this study was to evaluate the associations between alanine aminotransferase (ALT) and aspartate aminotransferase (AST) with metabolic syndrome (MetS) in the general Chinese population. Methods: This study was a multicenter, cross-sectional study which was conducted in rural areas of China from the 2012 to 2013 Northeast China Rural Cardiovascular Health Study (NCRCHS), and 11,573 adults with complete data were included in our final analysis. Elevated ALT and AST levels were defined as >40 U/L. Serum ALT and AST levels within the reference range were divided into quartiles, and their associations with MetS were evaluated by logistic regressions. Results: A total of 7.4% and 3.5% participants had elevated serum ALT and AST levels, respectively. The prevalence of MetS was 37.3% in males and 45.8% in females. After adjusting for potential confounders, we found ALT level elevation, even within the reference range, was independently associated with MetS. The odds ratio (OR) values of MetS in the ALT quartiles 2–4 groups within the reference range were 1.113 (95% CI: 1.019–1.280), 1.375 (95% CI: 1.212–1.560), 1.878 (95% CI: 1.650–2.138) compared with the ALT quartile 1 group, and OR in the elevated ALT group was 3.020 (95% CI: 2.496–3.653). Positive relationship for MetS was also observed in elevated AST group (OR: 1.689, 95% CI: 1.314–2.171), but within the reference range, the AST level was not associated with MetS. Conclusions: Serum ALT level, even within the reference range, was significantly associated with MetS. However, only elevated AST levels above 40 U/L was positively associated with MetS. Within the reference range, we did not find a relationship between AST levels and MetS.

Protective effect of diallyl trisulfide against naphthalene-induced oxidative stress and inflammatory damage in mice.

The aim of this study was to investigate the possible protective effects of diallyl trisulfide (DATS) against naphthalene-induced oxidative and inflammatory damage in the livers and lungs of mice. Elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels showed significant hepatic damage after the challenge with 100 mg/kg naphthalene. Hepatic malondialdehyde (MDA) contents and the activity of myeloperoxidase (MPO) increased significantly, accompanying a decrease in the hepatic activity of total superoxide dismutase (SOD) and glutathione (GSH) levels after the naphthalene damage. In addition, the serum levels of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 8 (IL-8) increased significantly in the groups damaged with naphthalene. The main parameters related to oxidative stress and inflammatory responses in the lungs, including the NO, MPO, and GSH contents, were determined, and the histopathological and immunohistochemical changes in the lung and liver tissues were also observed. In the DATS-treated groups, all of the oxidative and inflammatory damage in the serum, liver, and lung tissues were significantly prevented.

Gab1 adaptor protein acts as a gatekeeper to balance hepatocyte death and proliferation during acetaminophen-induced liver injury in mice.

Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure. In APAP-induced acute liver failure, hepatocyte death and subsequent liver regeneration determines the prognosis of patients, making it necessary to identify suitable therapeutic targets based on detailed molecular mechanisms. Grb2-associated binder 1 (Gab1) adaptor protein plays a crucial role in transmitting signals from growth factor and cytokine receptors to downstream effectors. In this study, we hypothesized that Gab1 is involved in APAP-induced acute liver failure. Hepatocyte-specific Gab1 conditional knockout (Gab1CKO) and control mice were treated with 250 mg/kg of APAP. After APAP treatment, Gab1CKO mice had significantly higher mortality and elevated serum alanine aminotransferase levels compared to control mice. Gab1CKO mice had increased hepatocyte death and increased serum levels of high mobility group box 1, a marker of hepatocyte necrosis. In addition, Gab1CKO mice had reduced hepatocyte proliferation. The enhanced hepatotoxicity in Gab1CKO mice was associated with increased activation of stress-related c-Jun N-terminal kinase (JNK) and reduced activation of extracellular signal-regulated kinase and AKT. Furthermore, Gab1CKO mice showed enhanced mitochondrial translocation of JNK accompanied by an increase in the release of mitochondrial enzymes into the cytosol, which is indicative of increased mitochondrial dysfunction and subsequent nuclear DNA fragmentation. Finally, in vitro experiments showed that Gab1-deficient hepatocytes were more susceptible to APAP-induced mitochondrial dysfunction and cell death, suggesting that hepatocyte Gab1 is a direct target of APAP-induced hepatotoxicity. Our current data demonstrate that hepatocyte Gab1 plays a critical role in controlling the balance between hepatocyte death and compensatory hepatocyte proliferation during APAP-induced liver injury.

Protective effect of Rabdosia amethystoides (Benth) Hara extract on acute liver injury induced by Concanavalin A in mice through inhibition of TLR4-NF-κB signaling pathway

Extract of Rabdosia amethystoides (Benth) Hara (ERA), a traditional Chinese medicine has antibacterial, antiviral, anti-tumor, anti-hepatitis and anti-inflammatory properties. However, the hepatoprotective effects and molecular mechanisms of ERA on acute liver injury have not been fully elucidated. This study aims to investigate the anti-inflammatory effect and liver protection of ERA against the acute liver injury induced by Concanavalin A (Con A) and its underlying molecular mechanisms in mice. Mice received ERA (50, 100, 150 mg/kg body weight) by gavage before Con A intravenous administration. We found that ERA pretreatment was able to significantly reduce the elevated serum alanine and aspartate aminotransferase levels and liver necrosis in Con A-induced hepatitis. In addition, ERA treatment significantly decreased the myeloperoxidase, malondialdehyde levels and augmented superoxide dismutase level in the liver tissue, and also suppressed the secretion of proinflammatory cytokines in the serum, compared with Con A group by enzyme linked immunosorbent assay. Furthermore, we observed that ERA pretreatment can significantly decrease the expression level of Toll-like receptor (TLR) 4 mRNA or protein in liver tissues. Further results showed that ERA pretreatment was capable of attenuating the activation of the NF-κB pathway by inhibiting IκBα kinase and p65 phosphorylation in Con A-induced liver injury. Our results demonstrate that ERA pretreatment has hepatoprotective property against Con A-induced liver injury through inhibition of inflammatory mediators in mice. The beneficial effect of ERA may be mediated by the downregulation of TLR4 expression and the inhibition of NF-κB activation.

Ameliorative Effect of Ginger Extract on Serum Biochemical Alterations in Diethylnitrosamine Treated Rats

Present work was designed to study ameliorative effect of ginger extract (GE) on serum biochemical alterations in diethylnitrosamine (DEN) treated rats. Fifty one male Wistar albino rats were randomly allotted to four groups. DEN (0.01%) was given in drinking water ad libitum and ginger extract (50 mg/kg BW) was administered in olive oil per os either alone or in combination for 90 days. Hypoproteinaemia, hypoalbuminaemia, hypoglycaemia, elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gammaglutamyl transferase (GGT) and total cholesterol levels were observed in the DEN treated rats. Concurrent administration of ginger extract with DEN significantly (P<0.05) alleviated the effects of DEN on serum enzyme level and other parameters. To conclude, present study demonstrated the ameliorative effect of ginger extract in partial to complete reversal in serum biochemical alterations.

Treatment of chronic HCV Genotype 1 infection with Boceprevir in German real-life:The impact of SVR on initially elevated and initially normal serum alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) levels

Background: Patients (pts) with chronic HCV G1 infection may present with normal or elevated serum ALT or GGT levels. The aim of the present analysis was to investigate the effect of successful treatment of chronic HCV G1 infection with boceprevir (BOC) triple therapy on initially elevated and initially normal ALT and GGT levels.

Association between elevated serum alanine aminotransferase and cardiometabolic risk factors in rural Chinese population: a cross-sectional study.

BackgroundElevated alanine aminotransferase (ALT) levels may be associated with metabolic syndrome and cardiovascular diseases. This study aimed to investigate the association between elevated ALT levels and cardiometabolic risk factors in a rural Chinese population.MethodsThis was a cross-sectional study conducted from July 2012 to August 2013, including 11,573 subjects (5,357 men and 6,216 women) aged ≥35 years in rural areas of Liaoning Province. A physical examination was performed and metabolic indicators were examined under standard protocols. Subjects were divided into those with elevated ALT levels (>40U/L) and those with normal ALT levels (≤40U/L).ResultsParticipants with elevated ALT levels had higher levels of almost all cardiometabolic risk factors than those with normal ALT levels. In individuals with elevated ALT levels, weight, height, waist circumference, and body mass index (BMI), which are indicators for general and abdominal obesity, were significantly higher (p < 0.001) than those in individuals with normal ALT levels. There was no significant difference in race, current smoking, or physical activity between the two groups. Other cardiometabolic risk factors, such as systolic blood pressure, diastolic blood pressure, and fasting plasma glucose, TC, TG, low-density lipoprotein cholesterol, and serum uric acid levels, were higher in participants with elevated ALT levels than in those with normal ALT levels. Logistic regression analysis showed that male sex, younger age, and the presence of high TC, high TG, and low high-density lipoprotein cholesterol levels, current smoking status, BMI ≥25 kg/m2, abdominal obesity, hyperuricemia, and HtgW phenotype were significantly (p < 0.05) associated with elevated ALT levels. Sex-related differences were also investigated. For men, hypertension (OR 1.33, 95 % CI 1.08–1.62), high TC levels (OR 1.63, 95 % CI 1.23–2.17), high TG levels (OR 1.62, 95 % CI 1.25–2.09), BMI ≥25 kg/m2 (OR 1.52, 95 % CI 1.07–2.18), and hyperuricemia (OR 1.92, 95 % CI 1.52–2.40) were significantly (p < 0.05) related to elevated serum ALT levels, but this was not observed in women.ConclusionsThere are significant relationships of elevated ALT levels with cardiometabolic risk factors and several sex-related differences in rural Chinese. Elevated serum ALT levels are associated with a worse cardiac risk profile.

Pyrene is a Novel Constitutive Androstane Receptor (CAR) Activator and Causes Hepatotoxicity by CAR

Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous persistent environmental pollutants which are primarily formed from the incomplete combustion of organic materials. Many potential sources of human exposure to PAHs exist, including daily exposures from the ambient environment or occupational settings. PAHs have been found to cause harmful effects on human health. Here, we evaluated the adverse effects of pyrene, a common PAH, on the liver. The present study demonstrates that pyrene is able to activate mouse constitutive androstane receptor (CAR). CAR protein, as measured by Western blot analysis, was observed to translocate into the nucleus from the cytoplasm in mouse liver after exposure to pyrene. Utilizing CAR null mice, we identified that CAR mediates pyrene-induced hepatotoxicity. Increased relative liver weight, hepatocellular hypertrophy, and elevated serum alanine aminotransferase levels were found in wild-type but not CAR null mice after orally administered pyrene. We further show that pyrene induced the expression of mouse liver metabolism enzymes including CYP2B10, CYP3A11, GSTm1, GSTm3, and SULT1A1, and caused hepatic glutathione depletion in wild-type but not CAR null mice. Moreover, by luciferase reporter assay and quantitative real-time PCR analysis, pyrene was found to be a potential inducer of CYP2B6 expression via activation of human CAR in HepG2 cells and human primary hepatocytes. Our observations suggest that pyrene is a novel CAR activator and that CAR is essential for mediating pyrene-induced liver injury.

Hepatitis B virus reactivation and hepatitis in diffuse large B-cell lymphoma patients with resolved hepatitis B receiving rituximab-containing chemotherapy: risk factors and survival

IntroductionHepatitis B virus (HBV) reactivation has been reported in B-cell lymphoma patients with resolved hepatitis B (hepatitis B surface antigen [HBsAg]-negative and hepatitis B core antibody [HBcAb]-positive). This study aimed to assess HBV reactivation and hepatitis occurrence in diffuse large B-cell lymphoma (DLBCL) patients with resolved hepatitis B receiving rituximab-containing chemotherapy compared with HBsAg-negative/HBcAb-negative patients to identify risk factors for HBV reactivation and hepatitis occurrence and to analyze whether HBV reactivation and hepatitis affect the survival of DLBCL patients with resolved hepatitis B.MethodsWe reviewed the clinical data of 278 patients with DLBCL treated with rituximab-containing therapy between January 2004 and May 2008 at Sun Yat-sen University Cancer Center, China. Predictive factors for HBV reactivation, hepatitis development, and survival were examined by univariate analysis using the chi-square or Fisher’s exact test and by multivariate analysis using the Cox regression model.ResultsAmong the 278 patients, 165 were HBsAg-negative. Among these 165 patients, 6 (10.9%) of 55 HBcAb-positive (resolved HBV infection) patients experienced HBV reactivation compared with none (0%) of 110 HBcAb-negative patients (P = 0.001). Patients with resolved hepatitis B had a higher hepatitis occurrence rate than HBsAg-negative/HBcAb-negative patients (21.8% vs. 8.2%, P = 0.013). HBcAb positivity and elevated baseline alanine aminotransferase (ALT) levels were independent risk factors for hepatitis. Among the 55 patients with resolved hepatitis B, patients with elevated baseline serum ALT or aspartate aminotransferase (AST) levels were more likely to develop hepatitis than those with normal serum ALT or AST levels (P = 0.037, P = 0.005, respectively). An elevated baseline AST level was an independent risk factor for hepatitis in these patients. Six patients with HBV reactivation recovered after immediate antiviral therapy, and chemotherapy was continued. HBcAb positivity, HBV reactivation, or hepatitis did not negatively affect the survival of DLBCL patients.ConclusionsDLBCL patients with resolved hepatitis B may have a higher risk of developing HBV reactivation and hepatitis than HBsAg-negative/HBcAb-negative patients. Close monitoring and prompt antiviral therapy are required in these patients.

Serum aminotransferase levels and angiographic coronary artery disease in octogenarians

Elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels have been associated with metabolic syndrome (MS), insulin resistance (IR), diabetes, endothelial dysfunction, coronary atherosclerosis, and cardiovascular (CVS) events, in addition to diseases of the liver [ 1– 4]. Studies have also shown that elevated AST/ ALT ratio in women could predict severity of coronary atherosclerosis [ 3]. Hence, in recent years, there has been a renewed interest in using ALT and AST as biomarkers for assessment of CVS risk. Serum AST levels were first described as a biomarker for myocardial necrosis in the 1950s [ 5] but were replaced by other more sensitive and specific biomarkers like creatinine kinase myocardial b fraction (CKMB) and troponins.

Metagenomic profiling of the viromes of plasma collected from blood donors with elevated serum alanine aminotransferase levels.

In Japanese Red Cross (JRC) blood centers, blood collected from donors with serum alanine aminotransferase (ALT) levels of more than 60 U/L are disqualified even if serologically negative for transfusion-transmitted infections (TTIs). To assess potential risks of TTIs in plasma with elevated serum ALT levels in the current donor screening program of the JRC, we conducted a metagenomic analysis (MGA) of virome profiles in the plasma of blood donors with or without elevated serum ALT levels. Based on serum ALT levels, donors were classified into three groups: "high," more than 79 U/L; "middle," 61 to 79 U/L; and "low," less than 61 U/L. We individually analyzed 100 plasma samples from each group by MGA, employing shotgun sequencing. Viral sequences detected using MGA were partly confirmed using real-time polymerase chain reaction (PCR). Donors with high and middle ALT levels were significantly younger than those with low ALT levels, and more than 90% were males. Herpesviridae, Anelloviridae, Picornaviridae, and Flaviviridae sequences were identified in plasma samples, and their distribution and frequency were not significantly different among the three groups. The serum ALT test may be unsuitable for monitoring for additional risks of TTIs in blood donors who were negative for typical TTIs using serologic and nucleic acid tests. Although MGA is less sensitive than PCR, it remains the best technology to detect known viruses in these donors.

Transcriptomic analysis of hepatic responses to testosterone deficiency in miniature pigs fed a high-cholesterol diet

BackgroundRecent studies have indicated that low serum testosterone levels are associated with increased risk of developing hepatic steatosis; however, the mechanisms mediating this phenomenon have not been fully elucidated. To gain insight into the role of testosterone in modulating hepatic steatosis, we investigated the effects of testosterone on the development of hepatic steatosis in pigs fed a high-fat and high-cholesterol (HFC) diet and profiled hepatic gene expression by RNA-Seq in HFC-fed intact male pigs (IM), castrated male pigs (CM), and castrated male pigs with testosterone replacement (CMT).ResultsSerum testosterone levels were significantly decreased in CM pigs, and testosterone replacement attenuated castration-induced testosterone deficiency. CM pigs showed increased liver injury accompanied by increased hepatocellular steatosis, inflammation, and elevated serum alanine aminotransferase levels compared with IM pigs. Moreover, serum levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides were markedly increased in CM pigs. Testosterone replacement decreased serum and hepatic lipid levels and improved liver injury in CM pigs. Compared to IM and CMT pigs, CM pigs had lower serum levels of superoxide dismutase but higher levels of malondialdehyde. Gene expression analysis revealed that upregulated genes in the livers of CM pigs were mainly enriched for genes mediating immune and inflammatory responses, oxidative stress, and apoptosis. Surprisingly, the downregulated genes mainly included those that regulate metabolism-related processes, including fatty acid oxidation, steroid biosynthesis, cholesterol and bile acid metabolism, and glucose metabolism. KEGG analysis showed that metabolic pathways, fatty acid degradation, pyruvate metabolism, the tricarboxylic acid cycle, and the nuclear factor-kappaB signaling pathway were the major pathways altered in CM pigs.ConclusionsThis study demonstrated that testosterone deficiency aggravated hypercholesterolemia and hepatic steatosis in pigs fed an HFC diet and that these effects could be reversed by testosterone replacement therapy. Impaired metabolic processes, enhanced immune and inflammatory responses, oxidative stress, and apoptosis may contribute to the increased hepatic steatosis induced by testosterone deficiency and an HFC diet. These results deepened our understanding of the molecular mechanisms of testosterone deficiency-induced hepatic steatosis and provided a foundation for future investigations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1283-0) contains supplementary material, which is available to authorized users.

Relationships of elevated levels of serum hepatic enzymes and alcohol intake with arterial stiffness in men

Objective: The present study aimed to evaluate the relationships between elevated serum levels of hepatic enzymes and arterial stiffness and to investigate whether alcohol intake had a modifying effect on these relationships in Japanese men. Methods: A total of 647 eligible men aged 35–69 years who underwent measurement of brachial-ankle pulse wave velocity (baPWV) as an index of arterial stiffness were evaluated. Information on their lifestyle characteristics were obtained from a structured self-administered questionnaire. Serum biochemical factors, including alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), were determined. The serum ALT and GGT levels were divided into tertiles, and their associations with baPWV values were evaluated using general linear models adjusted for potential confounding factors. The interaction effects between serum hepatic enzymes and alcohol intake on baPWV were further evaluated. Results: Elevated serum ALT and GGT levels were proportionally associated with increased baPWV after adjusting for the multivariable covariates (P values for trend, 0.004 and 0.003, respectively). Further analyses revealed that the proportional associations between serum levels of hepatic enzymes and baPWV were striking in the subjects without alcohol intake but not in those with alcohol intake. The interaction effect between serum GGT level and alcohol intake on baPWV was significant (P for interaction, 0.042). Conclusion: These results demonstrate that elevated serum ALT and GGT levels are associated with increased arterial stiffness, independent of the classical atherosclerotic risk factors in Japanese men, and that the association of elevated serum GGT level with arterial stiffness differs according to alcohol intake.

Effect of Thymoquinone and Omega-3 on Intestinal Ischemia/Reperfusion Induced Hepatic Dysfunction in Rats

Intestinal Ischemia-Reperfusion (I/R) is a complex phenomenon causing local and remote tissue destruction and multiple-organ dysfunction. The present study investigates the effect of thymoquinone and omega-3 on intestinal I/R-induced hepatic dysfunction. Sixty four Wistar albino rats were randomly allocated into four experimental groups: sham control, intestinal I/R control, thymoquinone (10 mg/kg) and omega-3 (300 mg/kg) pre-treated groups respectively. Intestinal I/R model were established by clamping the superior mesenteric artery for 30 min followed by 60 min reperfusion. Serum levels of aspartate Amino Transferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP) were measured. Hepatic tissue contents of Malondialdehyde (MDA), reduced Glutathione (GSH), Myeloperoxidase (MPO) and Tumor Necrosis Factor alpha (TNF-α) and Superoxide Dismutase (SOD) activity were measured. Apoptosis in hepatic tissue cells was determined by immunities to chemical analysis of caspase-3. Hepatic histopathological examination was carried out. Intestinal I/R elevated serum AST, ALT and ALP levels. In-addition, hepatic tissue SOD activity and GSH content were decreased, while MDA, MPO and TNF-&alpha contents were increased. Pre-treatment with thymoquinone or omega-3 corrected the histopathological changes and serum AST, ALT, ALP levels as well as hepatic tissue activity of SOD and GSH contents. In-addition, hepatic tissue contents of MDA and MPO were decreased. Furthermore, immunohistochemical examination showed remarkable activation of caspase-3 activity in hepatic tissue after intestinal I/R, which were corrected by thymoquinone or omega-3 pre-treatment. The protective potential of thymoquinone and omega-3 on hepatic dysfunction could be attributed to the known antioxidant, antiapoptotic and anti-inflammatory effects of test drugs.

Beneficial effects of phosphatidylcholine on high-fat diet-induced obesity, hyperlipidemia and fatty liver in mice

AimsSoybean-derived PC is an essential cell membrane phospholipid that is composed of unsaturated fatty acids, including oleic acid. The present study aimed to evaluate the potential alleviation effects of soybean PC on high fat diet (HFD)-induced obesity and its related complications. Main methodsWe fed C57BL/6 mice a HFD for 12weeks and administered PC orally for 8 or 12weeks at different doses. At the end of the experiment, blood was prepared for biochemical analysis and leptin ELISA. Aorta, epididymal and mesenteric fat and liver were removed surgically, weighed and observed for histological or immunohistochemical changes. Key findingsPC significantly prevented body weight gain and lipid accumulation and alleviated hyperlipidemia by decreasing triglyceride (TG) and total cholesterol (TC) levels and the atherogenic index in serum or by increasing the HDL/TC ratio. Aortic apoE expression and serum leptin levels were suppressed by PC treatment in the HFD-induced obese mouse model. Elevated serum aspartate aminotransferase and alanine aminotransferase levels in HFD-fed mice were decreased in the PC groups. PC treatment significantly decreased HFD-induced liver weight and hepatic lipid accumulation. SignificancePC treatment alleviated HFD-induced obese status and obesity-related complications such as hyperlipidemic changes that induce cardiovascular disease and NAFLD.

Randomized controlled trial of the CGRP receptor antagonist telcagepant for migraine prevention.

To evaluate whether the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant might be effective for migraine prevention. In this randomized, double-blind, placebo-controlled, multicenter trial (ClinicalTrials.gov NCT00797667), patients experiencing 3-14 migraine days during a 4-week baseline were randomized to telcagepant 140 mg, telcagepant 280 mg, or placebo twice daily for 12 weeks. Efficacy was assessed by mean monthly headache days and migraine/probable migraine days (headache plus ≥ 1 associated symptom). The trial was terminated following a recommendation from the Safety Monitoring Board due to hepatotoxicity concerns. At termination, the planned 660 patients had been randomized, 656 had been treated with ≥ 1 dose of study medication, and 14 had completed the trial. The mean treatment duration was 48-50 days. Thirteen patients, all in the telcagepant groups, had an alanine aminotransferase (ALT) elevation ≥ 3 × the upper limit of normal and 7 of these also had an aspartate aminotransferase elevation ≥ 3 × the upper limit of normal. Two patients had very high symptomatic transaminase elevations that occurred within 2-6 weeks of treatment initiation and resolved after treatment discontinuation. The originally planned efficacy analysis over 12 weeks was not performed due to limited data at later time points, but there was evidence that telcagepant resulted in a larger reduction from baseline than placebo for mean monthly headache days (month 1: 140 mg = -2.9, 280 mg = -3.1, placebo = -1.7; p < 0.05) and migraine/probable migraine days (month 1: 140 mg = -2.7, 280 mg = -3.0, placebo = -1.6; p < 0.05). These data suggest a potential role for CGRP receptor antagonism in migraine prophylaxis. However, the observed aminotransferase elevations do not support the use of telcagepant for daily administration. This study provides Class II evidence that in patients with migraine, telcagepant taken daily reduces headache days by 1.4 days per month compared to placebo and causes 2.5% of patients to have elevations of serum ALT levels.

Betanin attenuates paraquat-induced liver toxicity through a mitochondrial pathway

We attempted to determine whether betanin (from natural pigments) that has anti-oxidant properties would be protective against paraquat-induced liver injury in Sprague–Dawley rats. Paraquat was injected intraperitoneally into rats to induce liver toxicity. The rats were randomly divided into four groups: a control group, a paraquat group, and two groups that received betanin at doses of 25 and 100mg/kg/day three days before and two days after they were administered paraquat. We evaluated liver histopathology, serum liver enzymatic activities, oxidative stress, cytochrome P450 (CYP) 3A2 mRNA expression, and mitochondrial damage. The rats that were injected with paraquat incurred liver injury, evidenced by histological changes and elevated serum aspartate aminotransferase and alanine aminotransferase levels; paraquat also led to oxidative stress, an increase of cytochrome P450 3A2 mRNA expression, and mitochondrial damage, indicated by mitochondrial membrane swelling, reduced mitochondrial cytochrome C, and apoptosis-inducing factor protein levels. Pathological damage and all of the above mentioned markers were lesser in the animals treated with betanin than in those who received paraquat alone. Betanin had a protective effect against paraquat-induced liver damage in rats. The mechanism of the protection appears to be the inhibition of CYP 3A2 expression and protection of mitochondria.

Evaluation of the Antibody Response against Hepatitis C Virus Infection in Patients on Maintenance Hemodialysis (MHD): A Pilot Study

Majority of the patients with end stage renal disease (ESRD) are on maintenance hemodialysis (MHD) in Bangladesh. Dialysis patients are at high risk for contracting blood borne infection including hepatitis C virus (HCV) infection. The aim of this study was to evaluate the antibody response of hepatitis C virus infection in patients on MHD by detecting different viral markers in blood. A total of 88 patients with chronic kidney disease (CKD)were recruited from BIRDEM and BSMMU during the period from June 2006 to June 2007. Of them 63 patients on MHD and 25 predialysis patients were taken as cases and controls respectivly. Anti-HCV antibody were positive in 38% of dialysis patients but none of the controls were positive for Anti-HCV. When HCV positive MHD patients (38%) were compared to HCV negative MHD patients (62%), it showed that HCV positive patients had longer duration of dialysis (24±25 vs 9±6 months, p&lt;0.001), increased number blood transfusions (29±34 vs 10±9 units, p&lt;0.004) and elevated serum alanine aminotransferase level (35±23 vs 20±9 U/L, p=0.001). Implementing comprehensive infection control program by routine screening of the CKD patients, safe blood transfusion program, reducing transfusion of blood by use of erythropoietin and proper disinfection and cleaning of hemodialysis units may reduce the infection by HCV Virus. DOI: http://dx.doi.org/10.3329/bjmb.v7i1.18573 Bangladesh J Med Biochem 2014; 7(1): 9-13