Serum Liver Enzyme Concentrations Research Articles

Keeping patients in the dark: perioperative anesthetic considerations for patients receiving 5-aminolevulinic acid for glioma resection.

5-Aminolevulinic acid hydrochloride (5-ALA), available under the trade name Gleolan, is an orally administered fluorophore drug used to enhance visual differentiation of cancerous tissue from healthy tissue, primarily during surgical resection of high-grade gliomas. Although given preoperatively, 5-ALA has important implications for anesthetic care throughout the perioperative period. This article reviews pharmacology, safety concerns, and perioperative considerations for patients who receive oral 5-ALA. Although approved for clinical use by the United States Food and Drug Administration in 2017, studies and case reports published since then have further delineated side effects of this medication and its mechanisms and pharmacokinetics. Mitigating the possible side effects of 5-ALA requires an understanding of its basic mechanism as well as focused perioperative planning and communication. Administration of this medication may result in nausea, vomiting, photosensitivity, increase in serum concentration of liver enzymes, and hypotension. Patients who receive 5-ALA must be protected from prolonged light exposure during the first 48 h after consumption and administration of other photosensitizing agents should be avoided (Supplemental Video File/Video abstract).

The effect of coenzyme Q10 supplementation on liver enzymes: A systematic review and meta-analysis of randomized clinical trials.

Coenzyme Q10 is a potent antioxidant and is necessary for energy production in mitochondria. Clinical data have suggested that coenzyme Q10 (CoQ10) has some beneficial effects on liver function. However, these results are equivocal. This systematic review and meta-analysis aimed to clarify the effect of coenzyme Q10 supplementation on the serum concentration of liver function enzymes. We searched the online databases using relevant keywords up to April 2022. Randomized clinical trials (RCTs) investigating the effect of CoQ10, compared with a control group, on serum concentrations of liver enzymes were included. We found a significant reduction following supplementation with CoQ10 on serum concentrations of alanine aminotransferase (ALT) based on 15 effect sizes from 13 RCTs (weighted mean difference [WMD] = -5.33 IU/L; 95% CI: -10.63, -0.03; p = .04), aspartate aminotransferase (AST) based on 15 effect sizes from 13 RCTs (WMD = -4.91 IU/L; 95% CI: -9.35, -0.47; p = .03) and gamma-glutamyl transferase (GGT) based on eight effect sizes from six RCTs (WMD = -8.07 IU/L; 95% CI: -12.82, -3.32; p = .001; I 2 = 91.6%). However, we found no significant effects of CoQ10 supplementation on alkaline phosphatase concentration (WMD = 1.10 IU/L; 95% CI: -5.98, 8.18; p = .76). CoQ10 supplementation significantly improves circulating ALT, AST, and GGT levels; therefore, it might positively affect liver function. Further high-quality RCTs with more extended intervention periods and larger sample sizes are recommended to confirm our results.

Combined non-alcoholic fatty liver disease and type 2 diabetes in severely obese patients-medium term effects of sleeve gastrectomy versus Roux-en-Y-gastric bypass on disease markers.

We aimed to evaluate the medium-term efficacy of sleeve gastrectomy (SG) vs. Roux-en-Y gastric bypass (RYGB) on remission of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). We identified severely obese patients [body mass index (BMI) >35 kg/m2] with NAFLD (as defined by the Longitudinal Assessment of Bariatric Surgery Study) and T2DM (as defined by the American Association of Clinical Endocrinologists and the American College of Endocrinology) who underwent SG or RYGB in a single university surgical centre. The cohorts were match-paired and data were analysed after at least 3 years of follow up. The key outcomes measured were: (I) the improvement of liver function tests and NAFLD markers; (II) glycemic control and insulin resistance. Ninety-six patients were investigated; 44 (45.8%) were women. The mean pre-operative BMI was 45.2 kg/m2 in the SG and 42.0 kg/m2 in the RYGB group. SG and RYGB both significantly reduced serum liver enzyme concentrations. NAFLD markers resolved 2 years after SG in all patients. In contrast, only 78% and 80% of patients achieved remission of NAFLD 2 and 3 years after RYBG respectively. Both procedures resulted in comparable rates of remission of T2DM. Bariatric surgery with SG may be preferable to RYGB for obese patients with NAFLD and T2DM based on the rates of remission of markers of these co-morbidities. However, our results need to be confirmed in prospective trials. Understanding the metabolic effects of specific bariatric surgical procedures may facilitate the development of a personalised approach to weight-loss surgery.

Effectiveness of Grape Seed Extract in Patients with Nonalcoholic Fatty Liver: A Randomized Double-Blind Clinical Study

Background: Nonalcoholic fatty liver disease (NAFLD) as a metabolic disorder has a high prevalence. Increasing serum concentrations of liver enzymes, lipid profiles, and fasting blood sugar (FBS) are the most laboratory findings in NAFLD. Efforts to identify effective treatments with fewer side effects to address these impairments are increasing. Grape seed extract (GSE) is rich in antioxidants (eg, proanthocyanidins (Pas), which it has beneficial effects reported previously). Objectives: We evaluated the effect of GSE on biochemical markers in NAFLD patients. Methods: The current randomized, double-blind clinical trial was investigated the GSE effect on patients with NAFLD. The patients were assigned into 2 groups (GSE and control groups). The duration of treatment was considered 2 months. The GSE group received GSE capsules (200 mg, two times a day for 2 months), and the control group received placebo (200 mg starch). The serum concentration of aspartate aminotransferase (AST), triglyceride (TG), FBS, high-density lipoprotein (HDL), alanine aminotransferase (ALT), low-density lipoprotein (LDL), and cholesterol were assessed at baseline, 1 month, and 2 months after treatment. Body mass index (BMI) and HDL/LDL ratio were assayed at different times. Results: The levels of AST, ALT, FBS, TG, HDL, LDL, and cholesterol significantly decreased, (P-value < 0.05), and the level of HDL significantly increased in patients who received GSE 200 mg twice a day for 2 months (P-value < 0.05) compared to control group, but BMI and weight did not change significantly (P-value > 0.05). Conclusions: Grape seed extract can be effective in fatty liver patients; such results may be contributed to the antioxidant properties of GSE due to the high amount of PAs and similar constituents in GSE. However, more investigations are needed to clarify the exact involved mechanism of GSE.

Disease Status at Diagnosis in Danish Children with α 1 -antitrypsin Deficiency.

The aim of this cross-sectional study was to assess the state of disease at the time of diagnosis in Danish children with α 1 -antitrypsin deficiency as Denmark has a high prevalence of ZZ-homozygosity. Children either heterozygous, compound heterozygous, or homozygous for Z- and S-variants in the SERPINA1 -gene were included. Clinical characteristics, SERPINA1 -genotype, and blood serum (S) concentrations were recorded concurrently with genetic testing. Serum liver marker concentrations were compared using T tests and Wilcoxon-Mann-Whitney tests. Generalized estimating equation (GEE) linear regression models, both univariable and multivariable adjusted for age and sex, were applied to identify correlations with serum α 1 -antitrypsin (S-AAT). The relationship between S-AAT concentration and genotype was assessed using logistic regression with GEE. The study included 183 of 225 children genetically tested for alpha-1-antitrypsin deficiency (AATD). Of these, 36.6% were homozygous for the Z-variant. Of the heterozygotes, 89.7% had a ZM genotype and the remaining had either an MS genotype or were compound heterozygous. At diagnosis, ZZ-homozygous children had higher serum concentrations of liver enzymes and conjugated bilirubin, but lower concentrations of S-AAT compared with heterozygotes. Serum concentrations of conjugated bilirubin and liver enzymes were negatively associated with S-AAT. Children under 6 months of age had higher total S-bilirubin concentrations than children over 6 months of age. A low S-AAT concentration is a strong indicator of homozygosity, and homozygous children have higher enzymatic and cholestatic parameters compared with heterozygous children at diagnosis. This underlines the importance of measuring the S-AAT concentration in children with prolonged neonatal jaundice.

Multimodal Blockade of the Renin-Angiotensin System Is Safe and Is a Potential Cancer Treatment for Cats.

Simple SummaryAs activation of the renin-angiotensin system (RAS) promotes cancer cell growth, medications that inhibit RAS activation could reduce cancer progression. However, studies in people in which RAS has been inhibited by a single treatment have not been consistently beneficial, possibly as RAS can be activated by many different cellular pathways. Multiple treatments have been used to more consistently block RAS in people, but such multimodal treatments have never previously been evaluated in veterinary species. In the present study, the safety of multimodal RAS inhibition using a combination of five treatments was assessed in six cats with cancer. Cats were treated for 8 weeks and none of the cats developed low blood pressure, evidence of kidney or liver disease, or significant adverse effects. Of the six cats enrolled in the study, one cat was withdrawn from the study due to difficulties administering the medications and another cat died of an unrelated cause. Two cats were euthanatized due to cancer progression during the study period while two cats completed the 8-week treatment period. The study showed that a multimodal blockade of RAS has the potential to be a safe and cost-effective treatment for cancer in cats.The role of the renin-angiotensin system (RAS) in cancer growth and progression is well recognized in humans. However, studies on RAS inhibition with a single agent have not shown consistent anticancer effects, potentially due to the neoplastic cells utilizing alternative pathways for RAS activation. To achieve more complete RAS inhibition, multimodal therapy with several medications that simultaneously block multiple steps in the RAS has been developed for use in humans. In the present study, the safety of multimodal RAS inhibition using atenolol, benazepril, metformin, curcumin, and meloxicam was assessed in six cats with squamous cell carcinomas. Cats were treated for 8 weeks, with blood pressure measured and blood sampled five times during the treatment period. None of the cats developed hypotension, azotemia, or increased serum liver enzyme concentrations. The packed cell volume of one cat decreased to just below the reference range during treatment. One cat was reported to have increased vomiting, although this occurred infrequently. One cat was withdrawn from the study due to difficulties administering the medications, and another cat died of an unrelated cause. Two cats were euthanatized during the study period due to cancer progression. Two cats completed the 8-week study period. One was subsequently euthanized due to cancer progression while the other cat is still alive 32 weeks after entering the study and is still receiving the multimodal blockade of the RAS. This is the first evaluation of multimodal blockade of the RAS in veterinary species. The study showed that the treatment is safe, with only mild adverse effects observed in two treated cats. Due to the small number of cats, the efficacy of treatment could not be evaluated. However, evidence from human studies suggests that a multimodal blockade of RAS could be a safe and cost-effective treatment option for cancer in cats.

LBA01-07 OVERALL SAFETY AND INCIDENCES OF ADVERSE EVENTS BY TIME INTERVAL WITH DAROLUTAMIDE PLUS ANDROGEN-DEPRIVATION THERAPY AND DOCETAXEL IN THE PHASE 3 ARASENS TRIAL

You have accessJournal of UrologyCME1 May 2022LBA01-07 OVERALL SAFETY AND INCIDENCES OF ADVERSE EVENTS BY TIME INTERVAL WITH DAROLUTAMIDE PLUS ANDROGEN-DEPRIVATION THERAPY AND DOCETAXEL IN THE PHASE 3 ARASENS TRIAL E. David Crawford, Matthew R. Smith, Bertrand Tombal, Karim Fizazi, Maha Hussain, Cora N. Sternberg, Arash Rezazadeh Kalebasty, Ronald Tutrone, Neal D. Shore, Laurence Belkoff, Silke Thiele, Rui Li, Iris Kuss, Heikki Joensuu, and Fred Saad E. David CrawfordE. David Crawford More articles by this author , Matthew R. SmithMatthew R. Smith More articles by this author , Bertrand TombalBertrand Tombal More articles by this author , Karim FizaziKarim Fizazi More articles by this author , Maha HussainMaha Hussain More articles by this author , Cora N. SternbergCora N. Sternberg More articles by this author , Arash Rezazadeh KalebastyArash Rezazadeh Kalebasty More articles by this author , Ronald TutroneRonald Tutrone More articles by this author , Neal D. ShoreNeal D. Shore More articles by this author , Laurence BelkoffLaurence Belkoff More articles by this author , Silke ThieleSilke Thiele More articles by this author , Rui LiRui Li More articles by this author , Iris KussIris Kuss More articles by this author , Heikki JoensuuHeikki Joensuu More articles by this author , and Fred SaadFred Saad More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002669.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In ARASENS, darolutamide (DARO)+androgen-deprivation therapy (ADT)+docetaxel significantly reduced risk of death by 32.5% (hazard ratio [HR] 0.675; 95% confidence interval [CI] 0.568–0.801; P <0.0001) vs ADT+docetaxel in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC). We report adverse events (AEs) and their incidences by time interval from ARASENS (NCT02799602). METHODS: Pts with mHSPC were randomized 1:1 to DARO 600 mg twice daily or matching placebo (PBO)+ADT+docetaxel. AE incidences by time interval were defined as number of pts with new-onset AE or worsening AE in an interval (every 3 months for year 1; 6 months for year 2) divided by number of pts in that interval. For AEs associated with AR pathway inhibitors, exposure-adjusted incidence rates (EAIR) are presented per 100 pt years to adjust for differences in treatment duration between groups. RESULTS: Of 1306 pts randomized, safety was evaluated in 1302 pts who received DARO (652) or PBO (650). Incidences of any-grade AEs (99.5%; 98.9%), grade 3–5 AEs (70.2%; 67.5%), serious AEs (44.8%; 42.3%), and discontinuations of DARO/PBO due to AEs (13.5%; 10.6%) were comparable for both groups. The most frequently reported AEs were alopecia (40.5%; 40.6%), neutropenia (39.3%; 38.8%), and fatigue (33.1%; 32.9%); incidences in both groups were highest in the first 6 months of treatment during the docetaxel treatment period and progressively decreased thereafter (Table). Similar trends were observed for other AEs reported in >10% of pts in either treatment group, including peripheral edema, diarrhea, nausea, increased serum liver enzyme concentrations, and peripheral neuropathy. Most AEs associated with AR pathway inhibitors showed ≤2% difference between DARO and PBO. Rash (16.6%; 13.5%) and hypertension (13.7%; 9.2%) (both grouped preferred terms) occurred in more pts receiving DARO vs PBO, but EAIRs were similar between groups (rash: 6.2; 7.3; hypertension: 5.1; 5.0). CONCLUSIONS: DARO+ADT+docetaxel significantly increased overall survival without added toxicity. In general, AE incidence was similar in both groups, with the highest incidence during the first 6 months of overlapping docetaxel treatment. Source of Funding: Bayer AG and Orion Pharma © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1038 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information E. David Crawford More articles by this author Matthew R. Smith More articles by this author Bertrand Tombal More articles by this author Karim Fizazi More articles by this author Maha Hussain More articles by this author Cora N. Sternberg More articles by this author Arash Rezazadeh Kalebasty More articles by this author Ronald Tutrone More articles by this author Neal D. Shore More articles by this author Laurence Belkoff More articles by this author Silke Thiele More articles by this author Rui Li More articles by this author Iris Kuss More articles by this author Heikki Joensuu More articles by this author Fred Saad More articles by this author Expand All Advertisement PDF DownloadLoading ...

Transaminase Concentrations Cannot Separate Non-Alcoholic Fatty Liver and Non-Alcoholic Steatohepatitis in Morbidly Obese Patients Irrespective of Histological Algorithm

Background: In current general practice, elevated serum concentrations of liver enzymes are still regarded as an indicator of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). In this study, we analyzed if an adjustment of the upper limit of normal (ULN) for serum liver enzymes can improve their diagnostic accuracy. Methods: Data from 363 morbidly obese patients (42.5 ± 10.3 years old; mean BMI: 52 ± 8.5 kg/m²), who underwent bariatric surgery, was retrospectively analyzed. NAFL and NASH were defined histologically according to non-alcoholic fatty liver activity score (NAS) and according to steatosis activity fibrosis (SAF) score for 2 separate analyses, respectively. Results: In 121 women (45%) and 45 men (46%), elevated values for at least one serum parameter (ALT, AST, γGT) were present. The serum concentrations of ALT (p < 0.0001), AST (p < 0.0001) and γGT (p = 0.0023) differed significantly between NAFL and NASH, irrespective of the applied histological classification method. Concentrations of all 3 serum parameters correlated significantly positively with the NAS and the SAF score, with correlation coefficients between 0.33 (ALT/NAS) and 0.40 (γGT/SAF). The area under the curves to separate NAFL and NASH by liver enzymes achieved a maximum of 0.70 (ALT applied to NAS-based classification). For 95% specificity, the ULN for ALT would be 47.5 U/L; for 95% sensitivity, the ULN for ALT would be 17.5 U/L, resulting in 62% uncategorized patients. Conclusion: ALT, AST, and γGT are unsuitable for non-invasive screening or diagnosis of NAFL or NASH. Utilizing liver enzymes as an indicator for NAFLD or NASH should generally be questioned.

Coffee Consumption and Liver Health: Results From the UK Biobank

ObjectivesPrevious studies suggest a positive association between coffee consumption and liver health, yet the evidence available is not unequivocal. Given the burden of liver disease, we studied the relationship of habitual coffee consumption with serum biomarkers of liver health and non-alcoholic fatty liver disease (NAFLD) incidence. MethodsWe included 209,575 participants from the UK Biobank cohort (mean age 56.1 and 68% women, median coffee consumption per day 1.00 cup [0.50, 3.00]), free of disease at baseline. Firstly, we studied cross-sectional associations of coffee consumption with serum concentrations of the liver enzymes alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), and total bilirubin using multivariable linear regressions. Secondly, we analyzed associations with elevated enzyme concentrations according to clinical cutoffs to monitor liver damage, using logistic regressions. Lastly, in a longitudinal analysis, we assessed the association of coffee consumption and incident NAFLD in cox proportional hazard models. Models were adjusted for sociodemographic, lifestyle and health-related factors. Results are reported as β log transformed IU/L, odds ratio (OR) or hazard ratio (HR) with their 95% confidence intervals [95% CI] per one cup increase in coffee intake. ResultsOver a median follow up of 10.9 years, 2258 cases of incident NAFLD occurred in the population. Higher coffee consumption was associated with lower concentrations of log-transformed ALP (–0.005 [95% CI –0.006, –0.005]), ALT (–0.004 [–0.005, –0.003]), AST (–0.005 [–0.005, –0.004]), GGT (–0.008 [–0.009, –0.007]) and total bilirubin (–0.009 [–0.010, –0.008]). Secondly, higher coffee consumption was associated with lower odds of having elevated levels of all studied liver enzymes (OR from 0.91, [0.89, 0.92] for total bilirubin to 0.98 [0.97, 0.98] for GGT). Finally, higher coffee consumption was associated with lower risk of developing NAFLD (HR 0.98 [0.96, 0.99]). ConclusionsIn this large cohort we observed an inverse association between higher coffee consumption and serum concentrations of baseline liver enzymes and NAFLD risk. These findings suggest that habitual consumption of coffee may be protective of liver health. Funding SourcesN/A.

Assessment of Propolis Supplementation on Serum Concentrations of Liver Enzymes in Endurance Athletes with Four Weeks Aerobic Training

Background: Aerobic and intense exercises with an increase in free radicals cause damages at the cellular level, heart disease, cancer, and the development of aging processes, which one of its symptoms is increased serum concentrations of liver enzymes. Objective: The purpose of this study was to investigate the concurrent effect of four weeks of aerobic training and propolis supplementation on the activity of liver enzymes, including ALT, AST, and SOD in endurance athletes. Methods: Thirty-two male athletes (age: 21±1.4 years) in track and field were randomly divided into three groups: exercise group, exercise with placebo group, and exercise with supplement group. Propolis supplementation was taken as two tablets (500 mg) twice a day and aerobic exercise was performed for 4 weeks and in 24 sessions with an intensity of 60 to 65% of heart rate. The statistical method was done using one-way ANOVA and Tukey post hoc test by SPSS v. 18 software. Findings: The results showed that there was a statistically significant difference between groups in serum levels of SOD, AST, and ALT (P&lt;0.05). There was not a statistically significant difference between the exercise group and placebo+exercise group in serum levels of SOD, AST, and ALT (P&gt;0.05). Conclusion: The results showed that aerobic exercise alone can increase SOD levels and propolis supplementation with aerobic exercise can reduce AST and ALT serum levels and lead to improved liver cell function.

Genome-wide association study of serum liver enzymes implicates diverse metabolic and liver pathology

Serum liver enzyme concentrations are the most frequently-used laboratory markers of liver disease, a major cause of mortality. We conduct a meta-analysis of genome-wide association studies of liver enzymes from UK BioBank and BioBank Japan. We identified 160 previously-unreported independent alanine aminotransferase, 190 aspartate aminotransferase, and 199 alkaline phosphatase genome-wide significant associations, with some affecting multiple different enzymes. Associated variants implicate genes that demonstrate diverse liver cell type expression and promote a range of metabolic and liver diseases. These findings provide insight into the pathophysiology of liver and other metabolic diseases that are associated with serum liver enzyme concentrations.

Almond protects the liver in coronary artery disease: A randomized controlled clinical trial.

To compare the effect of Pakistani and American almonds on serum concentration of liver enzymes in coronary artery disease patients. The randomised controlled trial was conducted at the Cardiology Clinics of Aga Khan University Hospital, Karachi, from February to July, 2012, and comprised patients who were randomised into intervention PA and AA groups and the control NI groups. Subjects in the intervention groups were provided Pakistani and American varieties of almonds 10g/day respectively with instructions to soak them overnight, remove the skin and eat them before breakfast for 12 weeks. The control group underwent no intervention. Serum concentrations of aspartate transaminase, Alanine transaminase and gamma-glutamyl transferase were analysed and compared. Of the 150 subjects, 110(73.3%) completed the study. Of them, there were 38(34.5%) in PA group, 41(37.3%) in AA, and 31(28.2%) in the NI group. Dietary almonds significantly reduced serum concentrations of aspartate transaminase, alanine transaminase and gamma-glutamyl transferase in the two intervention groups compared to the controls group (p<0.05) at 12-week follow-up. A low dose of almonds was found to be an effective strategy to protect the liver.

The effect of saffron supplementation on some inflammatory and oxidative markers, leptin, adiponectin, and body composition in patients with nonalcoholic fatty liver disease: A double-blind randomized clinical trial.

Nonalcoholic fatty liver disease (NAFLD) is characterized by oxidative stress and inflammation in the hepatocytes. Saffron and its constituents are reported to have several properties such as anti-inflammatory and anti-diabetic effects. In a randomized double-blind placebo-controlled trial with two parallel groups including 76 eligible men and female patients with NAFLD aged 18-65, recruited from Hazrat Rasul Akram Hospital in Tehran, Iran. NAFLD was defined by a Gastroenterologist based on the American Gastrointestinal and Liver Association standards. Participants were randomly assigned to two groups receiving daily supplementation of either one tablet of 100 mg saffron (n = 38) or one placebo (n = 38) for 12 weeks. The primary outcome was high sensitive C-reactive protein (hs-CRP) and secondary outcomes were alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor alpha (TNF-α), malondialdehyde (MDA), total anti-oxidant capacity (TAC), leptin, adiponectin, anthropometric, and body composition Both groups were assigned similar diet and physical activity. In the treatment group, significant decreases in hs-CRP (-1.80 ng/ml, 95% CI = -2.97, -0.63, p = .032), leptin (-0.27 ng/ml, 95% CI = -0.65, -0.10, p = .040), MDA (-1.01 ng/ml, 95% CI = -1.89, -0.14, p = .023) and significant increase in TAC (0.34 μmol/L, 95% CI = 0.08, 0.61, p = .011) were observed compared to the placebo group. However, there were no significant changes in serum alanine aminotransferase, AST, TNF-α, body composition, and anthropometric indexes (p > .05). In the present study, 12 weeks of 100 mg of saffron supplementation indicated beneficial effects on serum levels of some inflammatory, oxidative stress, and adipokines biomarkers but it had no significant effect on serum concentrations of liver enzymes, anthropometric, and body composition measurements.

Evaluation of Prophylactic and Therapeutic Effects of Silymarin on Phenobar- bital-Induced Hepatotoxicity in Cats

BACKGROUND: Phenobarbital is one of the most commonly used drugs to treat epilepsy and other seizure disorders in dogs and cats. Hepatotoxicity following phenobarbital administration is dose-dependent. OBJECTIVES: The present study aimed to evaluate the protective action of silymarin on phenobarbital-in- duced hepatotoxicity in cats. METHODS: For this purpose, twenty-four healthy adult cats were randomly allotted to four equal groups. Cats in group A were given phenobarbital with dosage 16 mg/kg orally for 28 days; group B received silymarin (30 mg/kg/day for twenty-eight days) orally concurrent with phenobarbital; groups C and D were treated like group B, but silymarin was administered 3 and 48 h after administration of phenobarbital, respectively, and continued up to twenty-eight days. The serum concentrations of alanine aminotransferase, aspartate amino- transferase, alkaline phosphatase, lactate dehydrogenase, total and direct bilirubin, blood urea nitrogen and creatinine were measured before administration of phenobarbital and after 24 h, 72 h and 28 days. RESULTS:Phenobarbital elevated significantly serum concentrations of liver enzymes (in all cases), and total and direct bilirubin in two cats of group A, after 24 h (P 0.05), while in group D, levels of serum enzyme activities (in 4 cases) were higher than the normal values (P<0.001). CONCLUSIONS: The results showed that silymarin can protect liver tissue against oxidative stress in cats with phenobarbital intoxication especially in the first 3 h post-exposure.

Intestinal environmental disorders associate with the tissue damages induced by perfluorooctane sulfonate exposure.

Perfluorooctane sulfonate (PFOS) is a recently identified and persistent organic pollutant that becomes enriched in living organisms via bioaccumulation and the food chain. PFOS can induce various disorders, including liver toxicity, neurotoxicity and metabolic dysregulation. Most recent studies have shown a close association of the gut microbiota with the occurrence of diseases. However, few studies have explored the effects of PFOS on the gut environment, including the intestinal flora and barrier. In this study, we evaluated the effects of PFOS in C57BL/6J male mice and explored the relationship between tissue damage and the gut environment. Mice were orally exposed to PFOS for 16 days. Liver damage was assessed by examining the inflammatory reaction in the liver and serum liver enzyme concentrations. Metabolic function was assessed by the hepatic cholesterol level and the serum concentrations of glucose, high-density lipoprotein cholesterol, total cholesterol and triglycerides. Intestinal environmental disorders were assessed by evaluating the gut microbiota, SCFAs production, inflammatory reactions and intestinal tight junction protein expression. Our results indicated that PFOS affected inflammatory reactions in the liver and colon and promoted the development of metabolic disorders (especially of cholesterol and glucose metabolism). Moreover, PFOS dysregulated various populations in the gut microbiota (e.g., Firmicutes, Bacteroides, Proteobacteria, Gammaproteobacteria, Clostridiales, Enterobacteriales, Lactobacillales, Erysipelotrichaceae, Rikenellaceae, Ruminococcaceae and Blautia) and induced a loss of gut barrier integrity by reducing short-chain fatty acids (SCFAs) production and intestinal tight junction protein expression. A Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis mainly identified metabolic pathways (e.g., the adipocytokine signalling pathway), endocrine system pathways (e.g., steroid hormone biosynthesis, flavonoid biosynthesis), the latter of which is widely considered to be associated with metabolism. Overall, our results suggest that PFOS damages various aspects of the gut environment, including the microbiota, SCFAs and barrier function, and thereby exacerbates the toxicity associated with liver, gut and metabolic disorders.

The Hepatotoxic Effect of Sildenafil Citrate and Its Combination with Tramadol on Male Wistar Rats is Ameliorated with Vitamin E Supplementation

Aims: This study investigated the effect of vitamin E on serum liver enzymes and bilirubin concentrations in male Wistar rats treated with sildenafil citrate (SC) and a combination of SC and tramadol on the background that these drugs cause oxidative damage to the liver.&#x0D; Methods: Thirty male Wistar rats (180-200 g) were randomly divided into six groups (n=5) thus: control (0.2 ml vehicle – olive oil), SC-treated group (Sil) (10 mg/kg of SC), SC+tramadol-treated group (Sil+Tra) (10 mg/kg of SC and 20 mg/kg of tramadol), vitamin E-treated group (Vit E) (100mg/kg of vitamin E), SC+vitamin E-treated group (Sil+Vit E) (received SC and vitamin E) and SC+tramadol+vitamin E-treated group (Sil+Tra+Vit E) (received SC, tramadol and vitamin E). Drugs were administered orally once daily for four weeks after which blood samples were obtained and used to measure serum concentrations of liver enzymes (AST, ALT and ALP) and bilirubin.&#x0D; Results: Serum AST, ALT, ALP, total bilirubin (TB) and unconjugated bilirubin (UCB) concentrations were significantly (p&lt;0.001) increased in Sil and Sil+Tra compared with control and Vit E and significantly (p&lt;0.01) decreased in Sil+Vit E and Sil+Tra+Vit E compared with Sil and Sil+Tra. Serum conjugated bilirubin (CB) concentration and percentage conjugation of bilirubin significantly decreased (p&lt;0.001) in Sil and Sil+Tra compared with control and Vit E and increased (p&lt;0.01) in Sil+Vit E and Sil+Tra+Vit E compared with Sil and Sil+Tra.&#x0D; Conclusion: SC, administered separately and in combination with tramadol altered liver function. However, vitamin E supplementation was able to ameliorate this alteration in liver function.

Vedolizumab Therapy is Ineffective for Primary Sclerosing Cholangitis in Patients With Inflammatory Bowel Disease: A GETAID Multicentre Cohort Study.

Whether vedolizumab may be effective as a treatment for primary sclerosing cholangitis [PSC] in patients with inflammatory bowel disease [IBD] remains controversial. We performed a retrospective observational study of consecutive patients with IBD and PSC, treated with vedolizumab for at least 30 weeks in 22 centres of GETAID from January 2015 to June 2016. The outcomes included a decrease in the serum alkaline phosphatase [ALP] concentration of at least 50% from baseline to Week 30 or 54, a change in any serum liver enzymes concentrations, and an assessment of the efficacy and safety of vedolizumab in IBD. Among 75 patients with active IBD and PSC treated with vedolizumab, 21 patients discontinued vedolizumab before Week 30 [due to lack of efficacy in 19 and malignancy in two patients]. In the remaining 54 patients, a decrease in the serum ALP concentration of at least 50% from baseline to Weeks 30 and 54 was observed in four [7%] and four [11%] patients, respectively. No significant change was observed in serum liver enzyme concentrations at week 30 or 54. After a median follow-up period of 19.4 [14.0-29.9] months, nine cases of digestive neoplasia [colorectal neoplasia in seven and cholangiocarcinoma in two] were reported. In patients with IBD and PSC, vedolizumab did not improve serum liver enzyme concentrations at week 30 or 54. Nine cases of digestive cancer occurred during the follow-up period, confirming the need for a tight surveillance programme in this population.

Serum Liver Enzymes and Oxidative Stress Biomarkers in Resveratrol Treated Cholesterol Diet Induced Type 2 Diabetes Mellitus in Rabbits

Fat accumulation in the body has been implicated in the increased generation of ROS and oxidative stress which enhances hepatocellular damage. Increase in serum liver enzymes have been widely used as an index of liver dysfunction and that higher ALT concentrations predicted development of type 2 diabetes. Thirty rabbits were randomly divided into six groups, each of five animals: Group 1 = control (C), Group 2 = cholesterol diet (CD) only, Group 3 = resveratrol 200 mg/kg (R200), Group 4 = resveratrol 400 mg/kg (R400), Group 5 = CD + R200 and group 6 = CD + R400. The preparations were administered for 8 weeks of experimental protocol. Blood glucose level was measured on week zero and the 8th week of the treatment. At the end of the study period, the rabbits were placed under light anesthesia (ketamine) to remain unconscious. Blood sample of about 3ml was drawn via cardiac puncture for serum extraction which were evaluated for serum concentration of liver enzymes (alanine aminotransferase ALT, aspartate aminotransferase AST and alkaline phosphatase ALP) and oxidative stress biomarkers (superoxide dismutase SOD, catalase CAT and glutathione peroxidase GPx). Blood glucose level was significantly higher in CD group compared to groups that received resveratrol supplement. Serum Liver enzymes activities showed significant (P &lt; 0.05) decrease in ALT, AST and ALP levels in groups that were administered resveratrol with CD compared with CD alone. Significant decrease in antioxidant enzymes activities (SOD, CAT and GPx) in resveratrol treated groups (P &lt; 0.05) were recorded when compared to CD alone group. In conclusion, the observed decreased in blood glucose level, liver enzymes and biomarkers of oxidative stress with resveratrol administration despite CD consumptions, elucidated the therapeutic potential of resveratrol.Support or Funding Information1. SelfThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effects of Alpha-Lipoic Acid Supplementation on Oxidative Stress Status in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized, Double Blind, Placebo-Controlled Clinical Trial

Background: Several mechanisms have been suggested to explain the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and its progression, one of which is increased oxidative stress. Objectives: This study aimed to evaluate the effect of alpha-lipoic acid (ALA) supplementation on anthropometric indices, dietary intake and oxidative stress-related parameters in obese patients with NAFLD. Methods: In this double-blind, placebo-controlled trial, 50 NAFLD patients were assigned to two groups of receiving 1200 mg ALA (two 600 mg capsules of ALA) and placebo (two 600 mg capsules of placebo) for 12 weeks. Serum liver enzymes, malondialdehyde (MDA) level, total antioxidant status (TAS), and the activities of copper-zinc superoxide dismutase (Cu/Zn-SOD) and glutathione peroxidase (GSH-Px) were assessed at baseline and after 12 weeks of intervention. Results: Serum concentrations of liver enzymes decreased significantly in the ALA group (P < 0.05 for all), while a noticeable decline was observed for alanine aminotransferase (ALT) in the placebo group (32.5 ± 18.9 vs. 25.9 ± 11.2; P = 0.034). Nonetheless, there were no significant differences between the study groups concerning serum liver enzymes concentrations post-intervention. Although ALA supplementation significantly reduced the serum concentration of MDA (2.52 ± 0.35 vs. 2.77 ± 0.49; P < 0.040) and increased serum TAS (1.73 ± 0.55 vs. 1.52 ± 0.34; P < 0.048), other oxidative stress-related parameters such as Cu/Zn-SOD and GSH-Px activities were not affected. Conclusions: These findings suggest that daily supplementation of 1200 mg alpha-lipoic acid (ALA) for 12 weeks improves oxidative stress markers in patients with nonalcoholic fatty liver disease (NAFLD) and it could be considered as adjunctive therapy for the prevention of NAFLD progression.

SEROEPIDEMIOLOGIC SURVEY OF CANINE LEPTOSPIROSIS IN NORTHERN TAIWAN DURING 2008–2015

Leptospirosis is an important infectious zoonosis that may cause life-threatening illness in both humans and animals. This study aimed to identify the serovars of Leptospira using the microscopic agglutination test (MAT) and the effect of season on serum-positive cases detected in National Taiwan University Veterinary Hospital from August 2008 to September 2015. This study also compared the characteristics of serum-positive and serum-negative cases. Among 159 suspected cases, 78 serum-positive (MAT titer [Formula: see text]) and 81 serum-negative cases were identified. In serum-positive cases, the most common pathogenic serovars were Canicola (18.2%), Icterohaemorrhagiae (23.6%), and Shermani (20.0%). Significantly more serum-positive cases were identified in fall (September to November) than other seasons ([Formula: see text]). Dogs aged 1–5 years (odds ratio [Formula: see text] 1.7) were more likely to be identified as being serum-positive cases of canine leptospirosis than serum-negative cases. However, no significant difference was observed regarding breed, gender, and regional distribution. The serum concentrations of liver enzymes, total bilirubin, blood urea nitrogen, and creatinine were elevated in both serum-positive and serum-negative cases, with no significance. White blood cell (WBC) counts of serum-positive cases were statistically higher than those of serum-negative cases ([Formula: see text]). In conclusion, more precaution must be taken with dogs aged 1–5 years because of their higher risk of leptospirosis; additionally, significantly elevated WBC count may be a suitable indicator in suspected cases of canine leptospirosis.