Alanine Aminotransferase Concentrations Research Articles

Toxicological Effects of Commonly Used Mosquito Coil Smoke on Liver and Lung Function in Rats

The utilization of mosquito coils as a household-level strategy for mosquito control is widely practiced in malaria-endemic regions spanning Africa, Asia, and South America. However, the continuous application of mosquito coils has prompted significant apprehensions concerning environmental and health implications. This research aims to evaluate the potential hepatic and pulmonary toxicities associated with the inhalation of mosquito coil smoke in rat subjects over both sub-chronic and chronic durations. A questionnaire was used to make inquiries regarding the prevalent types and brands of mosquito coils employed, the manner in which they are used, the durations for which they are utilized. A total of twenty-four albino rats were categorized into three distinct groups: the control group and two exposed groups. These groups were subjected to distinct brands of mosquito coil smoke across two distinct exposure regimens – a sub-chronic exposure lasting 4 weeks and a chronic exposure spanning 12 weeks. Following the exposure periods, blood samples were collected for the analysis of serum-based and biochemical markers, including serum aspartate aminotransferase (AST), alanine aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), bilirubin, serum bicarbonate, and Lactate dehydrogenase (LDH), oxygen saturation, C-reactive protein, total protein, and microscopic analysis of lung tissue and liver tissue. The histopathological analysis of lung tissue was appropriately included. However, the analysis of liver tissue was omitted. The results demonstrated a significant elevation in the levels of these biochemical markers among the exposed rats in comparison to the control group. Concurrently, a decrease in blood oxygen saturation was noted in the exposed rats when contrasted with the control group. Conversely, the serum concentrations of high-sensitivity C-reactive protein, total protein, and alanine aminotransferase (ALT) did not exhibit notable differences in relation to the control group. Additionally, microscopic analysis of lung tissue indicated the presence of histopathological lesions in the exposed rats, suggesting a detrimental impact of mosquito coil smoke exposure in a time-dependent progression.

Effects of electroacupuncture of different intensities and durations on PERK/ATF4/CHOP signaling pathway in liver of non-alcoholic fatty liver disease rats.

To analyze the effects of electroacupuncture (EA) at "Fenglong" (ST40) and "Zusanli" (ST36) of different intensities and durations on rats with non-alcoholic fatty liver disease (NAFLD) based on the protein kinase R-like endoplasmic reticulum kinase (PERK)-activating transcription factor 4 (ATF4)-C/EBP homologous protein (CHOP) signaling pathway, so as to explore its mechanism underlying improvement of NAFLD. SD rats were randomly divided into normal diet group, high-fat model group, sham EA group, strong stimulation EA (SEA) group, and weak stimulation EA (WEA) group, with 15 rats in each group. Each group was further divided into 2, 3, and 4-week subgroups. NAFLD rat model was established by feeding a high-fat diet. After successful modeling, rats in the SEA and WEA groups received EA at bilateral ST40 and ST36 with dense and sparse waves (4 Hz/20 Hz) at current intensities of 4 mA (SEA group) and 2 mA (WEA group), lasting for 20 minutes, once a day, 5 days a week with 2 days of rest. The sham EA group only had the EA apparatus connected without electricity. Different duration subgroups were intervened for 2, 3, and 4 weeks. After the intervention, the contents of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in rats were detected by an automatic biochemical analyzer；liver morphological changes were observed by Oil Red O staining；real-time fluorescence quantitative PCR and Western blot were used to detect the expression of PERK, ATF4, and CHOP mRNAs and proteins in the rat liver tissue. In the high-fat model group, there was a significant accumulation of red lipid droplets in the liver cells, which was reduced significantly in the SEA group at the 4th week. Compared with the normal diet group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs and proteins in the liver tissue were elevated (P<0.01) in the high-fat model group . Compared with the high-fat model group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, CHOP mRNAs and proteins in the liver tissue were decreased (P<0.01, P<0.05) in the SEA and WEA groups. Compared with the sham EA group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs were decreased (P<0.01, P<0.05) in the SEA and WEA groups, the expression of PERK, ATF4, and CHOP proteins in the liver tissue was decreased (P<0.01) in the SEA group at the 2nd, 3rd, and 4th week, the expression of PERK and CHOP proteins at the 2nd, 3rd, 4th week and ATF4 protein at 2nd week in the liver tissue were decreased (P<0.01, P<0.05) in the WEA group. Compared with the SEA group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs and proteins in the liver tissue were elevated (P<0.05, P<0.01) in the WEA group. Compared with the 2-week time point within the groups, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs and PERK proteins in the liver tissue were decreased (P<0.01, P<0.05) in the SEA and WEA groups at 3rd and 4th week, the expression of ATF4 proteins in the liver tissue was decreased (P<0.01) in the SEA group at 3rd and 4th week, and the expression of CHOP proteins in the liver tissue was decreased (P<0.01) in the SEA group at 4th week and in the WEA group at 3rd and 4th week. Compared with the 3-week time point within the groups, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs were significantly decreased (P<0.05, P<0.01) in the SEA and WEA groups at 4th week, the expression of PERK and CHOP proteins in the liver tissue was decreased (P<0.01) in the SEA and WEA groups at 4th week, and the expression of ATF4 protein in the liver tissue was decreased (P<0.05) in the SEA group at 4th week. EA at ST40 and ST36 can significantly improve liver function in NAFLD rats, and its mechanism of action may involve inhibiting PERK expression thereby targeting the downstream ATF4/CHOP signaling pathway to suppress endoplasmic reticulum stress, exerting a liver protective effect；the optimal effect was observed with EA intensity of 4 mA for 4 weeks.

Cabozantinib monotherapy for advanced adrenocortical carcinoma: a single-arm, phase 2 trial

Adrenocortical carcinoma is a rare malignancy with poor response to systemic chemotherapy. Mitotane is the only approved therapy for adrenocortical carcinoma. Cabozantinib is a multikinase inhibitor approved in multiple malignancies. This is the first prospective trial to explore the anti-tumour activity, safety, and pharmacokinetic profile of cabozantinib in patients with advanced adrenocortical carcinoma. This investigator-initiated, single-arm, phase 2 trial in adult patients (aged ≥18 years) with advanced adrenocortical carcinoma was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). Eligible patients had histologically confirmed adrenocortical carcinoma, were not candidates for surgery with curative intent, had measurable disease, had an estimated life expectancy of at least 3 months, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 with adequate organ function. Patients who had used mitotane within 6 months of study participation were required to have a serum mitotane level of less than 2 mg/L. Patients were given oral cabozantinib 60 mg daily with the option of dose reduction to manage adverse events. The primary endpoint was progression-free survival at 4 months, assessed in all patients who received at least one dose of study drug per protocol. This study is registered with ClinicalTrials.gov, NCT03370718, and is now complete. Between March 1, 2018, and May 31, 2021, we enrolled 18 patients (ten males and eight females), all of whom received at least one dose of study treatment. Of the 18 patients, eight (44%) had an ECOG performance status of 0, nine (50%) patients had a performance status of 1, and one (6%) patient had a performance status of 2. Median follow-up was 36·8 months (IQR 30·2-50·3). At 4 months, 13 (72·2%; 95% CI 46·5-90·3) of 18 patients had progression-free survival and median progression-free survival was 6 months (95% CI 4·3 to not reached). One patient remains on treatment. Treatment-related adverse events of grade 3 or worse occurred in 11 (61%) of 18 patients. The most common grade 3 adverse events were lipase elevation (three [17%] of 18 patients), elevated γ-glutamyl transferase concentrations (two [11%] patients), elevated alanine aminotransferase concentrations (two [11%] patients), hypophosphatemia (two [11%] patients), and hypertension (two [11%] patients). One (6%) of 18 patients had grade 4 hypertension. No treatment related deaths occurred on study. Cabozantinib in advanced adrenocortical carcinoma showed promising efficacy with a manageable and anticipated safety profile. Further prospective studies with cabozantinib alone and in combination with immune checkpoint therapy are ongoing. Exelixis.

Drinking magnetized water alters blood constituents, and structure of spleen and kidney in rabbits

This study aimed to investigate the effect of magnetic field on physicochemical properties of water and evaluating the effects of the magnetized water (MW ) on the productive performance, liver enzymes, spleen and kidney structure of rabbits. Water samples were collected to determine pH and electrical conductivity (EC), and water structure was investigated by Transmission Electron Microscopy (TEM). Twenty-four weaned Rex rabbits, 21 d old, were allotted into two experimental groups: the first group was assigned as control, received regular tap water (TW), and the treated group, received MW, for 5 weeks. Productive traits were recorded weekly and at the end of the experiment, blood samples, spleen and kidney were collected for examinations. Results showed that pH and EC of MW were higher than those of TW. In addition, the arrangement MW cluster showed a unique alteration on the nano-scale. Growth performance indicators were similar in both experimental treatments, except FCR of the MW rabbits was better than that of the TW rabbits. The MW had no significant effect on plasma concentration of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and creatinine in growing Rex rabbits received MW in comparison with those received regular TW. Spleen histological structure of rabbits of both groups was normal. However, the epithelial cells lining renal tubules of kidneys of rabbits in MW group appeared large with basophilic nuclei in comparison with TW group. Conclusively, magnetic field alters the physicochemical properties of water. The MW may consequently increase blood glucose level and spleen weight % and enhance kidney structure in growing rabbits. Moreover, more studies are still needed to know the benefits of providing the magnetized water to ‎animals. ‎

Anti-diabetic effect of &lt;i&gt;Eucalyptus camaldulensis&lt;/i&gt; (Red gum) leaf-supplemented diet in streptozotocin-induced diabetic rats

Purpose: To investigate the potential anti-diabetic effect of supplementing a diet with Eucalyptus camaldulensis leaves in streptozotocin (STZ) induced Wistar rats. &#x0D; Methods: Methanolic extract of E. camaldulensis was screened using gas chromatography-mass spectrometric analysis. After that, eighteen animals were separated into three groups: Group A served as control group. Group B, the diabetic control group, was induced with STZ, and Group C was induced with STZ and fed a 10 % E. camaldulensis leaf-supplemented diet for 14 days. Thereafter, rats were sacrificed, and fasting blood was collected for serum glucose, enzyme and protein activity tests. Organs were excised for biochemical and histological analysis. &#x0D; Results: The GC-MS fingerprint identified 17 constituents, with 2-hydroxy carbazole being the most abundant. Rats on the E. camaldulensis leaf-based diet for 14 days exhibited a significant decrease (p &lt; 0.05) in serum glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), amylase, albumin, total bilirubin, urea, and creatinine concentrations compared to diabetic controls. Insulin levels significantly increased (p &lt; 0.05). Additionally, the E. camaldulensis diet led to a significant decrease in serum lipid profile levels but increased high-density lipoprotein cholesterol (HDL-C). Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities increased significantly, while malondialdehyde levels decreased significantly (p &lt; 0.05). Histopathology revealed positive effects on hepatocytes, acini, pancreatic duodenal lymphoid activation, islets of Langerhans resurgence, and normal kidneys. &#x0D; Conclusion: Eucalyptus camaldulensis leaf-supplemented diet demonstrates anti-diabetic, hypolipidemic and antioxidant enzyme activities. Carbazole identified by GC-MS may be the potential anti-diabetic and hypolipidemic agent in E. camaldulensis leaf-based diet.

Effects of Clothianidin on Biochemical Parameters of Adult Zebrafish

The ubiquitous use of insecticides leads to detrimental effects on non-target organisms due to accidental exposure. Neonicotinoid insecticides are popularly used worldwide for their high affinity for arthropod nicotinic receptors which effectively kill insect pests. Low affinity towards vertebrate nicotinic receptors, make them safer as compared to traditional insecticides. Recent studies demonstrated that neonicotinoid exposure can cause some toxicity in vertebrates including humans. Zebrafish is one of the popular model organisms to study ecotoxicity. This is the first study on adult zebrafish to report the effect of novel neonicotinoid, Clothianidin on mortality, liver antioxidant stress profile, liver function profile and brain acetylcholinesterase (AChE). Observations were made over two treatment periods, 96 hours, and 21 days, in five groups exposed to varying concentrations of Clothianidin viz. 30mg/L, 50mg/L, 70mg/L, 90mg/L, 110mg/L and a control. Although no mortality was observed, Clothianidin exposure led to increased activity of superoxide dismutase (SOD) enzyme, lipid peroxidation and decreased catalase (CAT), glutathione-S-transferase (GST). Treated groups also showed increased concentrations of liver enzyme alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and acid phosphatase (ACP). These results indicate that Clothianidin causes disturbances in the hepatic function. A prominent decreasing trend observed in brain AChE shows that Clothianidin inhibits AChE in adult zebrafish. Further investigations on DNA damage and gene expression studies could be conducted to understand the exact mechanism of action of Clothianidin

Conch Shell (Turbinella pyrum) Powder: A Potential Marine Biological Source of Calcium and Some Trace Minerals for Growing Crossbred Calves.

The present study was conducted to evaluate the effect of feeding conch shell (Turbinella pyrum) powder (either fresh or calcined) as a marine organic source of calcium (Ca) supplemented in the diet of crossbred calves on voluntary intake, growth performance, and blood biochemistry in growing crossbred Jersey calves. A growth trial of 90days was conducted on 15 Jersey crossbred female calves (Av. weight, 70.68 ± 2.90kg; Av. age, 197.73 ± 12.40days), equally divided into three groups of 5 animals each, i.e., control (T0), treatment 1 (T1), and treatment 2 (T2). All animals were fed total mixed ration (TMR) prepared with a concentrate mixture, chaffed paddy straw, and green fodder at the ratio of 40:30:30 on DM basis. Calves under the control group were fed with TMR containing a standard mineral mixture having dicalcium phosphate (DCP) as a Ca source. Calves under T1 group were supplemented with TMR containing fresh conch shell powder (FCSP), and T2 calves were fed with TMR containing conch shell calcined powder (CSCP) as Ca source. We observed 11.66% increase (p < 0.01) in Ca concentration in CSCP compared to FCSP. The concentration of minerals like Mg, Co, Mn, and Fe was enhanced in CSCP compared to the FCSP. However, the calcination process of fresh conch shell powder (FCSP) reduced the concentration of Cu, and Zn. The Ca/P ratio was estimated as 2.11, 2.06, and 2.10 in T0, T1, and T2 diets, which could be considered ideal for calf ration. Calves under T1, and T2 groups consumed significantly (p < 0.001) greater amounts (g/kg W0.75) of DM and CP compared to T0. However, increased voluntary intake did not translate into increased body weight gain (kg), and feed conversion ratio (kg DMI/kg gain) in T1 and T2 groups in comparison to T0. We observed similar blood glucose, urea, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine transaminase (ALT) concentration among the three treatments. Ca, and P levels in blood plasma were also identical among the three groups. The digestibility of Ca was increased significantly (p = 0.01) in FCSP (T1)- and CSCP (T2)-treated calves compared to control (T0) calves. Similarly, T1 and T2 enhanced P digestibility compared to T0. This first report with short-term experimentation depicted some promising scope for the use of locally available conch shell powder (fresh or calcined form) as a potential source of Ca for feeding to livestock, because these new sources of Ca did not affect intake, digestibility of Ca and P, growth performance, blood chemistry, and liver enzymes negatively in weaned crossbred calves.

Higher serum alanine aminotransferase levels and the incidence of hypertension: The Kailuan cohort study

ObjectiveThe association between serum alanine aminotransferase (ALT) concentrations and the incidence of hypertension remains unclear. To explore the association between serum ALT levels and the risk of incident hypertension based on the Kailuan cohort study. MethodsPeople who had participated in health check-ups in 2006–2007 without hypertension, cardiovascular, or liver diseases were enrolled and received follow-ups every two years until December 2017. Hypertension was defined as systolic blood pressure/diastolic blood pressure ≥140/90 mmHg or using anti-hypertensive medication. A multivariable-adjusted Cox regression model was used to estimate the hazard ratio (HR) and its corresponding 95 % confidence intervals (95 % CIs). ResultsDuring 10.5 years of follow-up, 24,023 (50.7 %) participants were diagnosed with hypertension. The HR of incident hypertension was 1.02 (95 % CI=1.01–1.03) for each 10 U/L increment of ALT concentrations. Participants with elevated ALT levels (>40 U/L) had an increased incidence of hypertension by 7 % (HR =1.07; 95 % CI=1.01–1.13). Besides, the HR was 1.10 (95 % CI=1.06–1.15), 1.13 (95 % CI=1.08–1.18), and 1.22 (95 % CI=1.16–1.30) (P for trend <0.001) in (10–20], (20–30], and (30–40] groups, compared with ≤10 U/L group. In addition, participants whose ALT levels decreased to the normal range at the first follow-up had a 23 % lower incidence of hypertension than those with elevated ALT levels at baseline and the first follow-up. ConclusionPeople with higher serum ALT levels may have an increased risk of incident hypertension and thus may benefit from heightened surveillance for hypertension and lifestyle interventions to reduce the risk of hypertension.

Exposure to Synthetic Psychoactive Substances: A Potential Cause for Increased Human Hepatotoxicity Markers.

Approximately 30 million people worldwide consume new psychoactive substances (NPS), creating a serious public health issue due to their toxicity and potency. Drug-induced liver injury is the leading cause of liver disease, responsible for 4% of global deaths each year. A systematic literature search revealed 64 case reports, in vitro and in vivo studies on NPS hepatotoxicity. Maximum elevated concentrations of aspartate aminotransferase (136 to 15 632 U/L), alanine transaminase (121.5 to 9162 U/L), total bilirubin (0.7 to 702 mg/dL; 0.04 to 39.03 mmol/L), direct (0.2-15.1 mg/dL; 0.01-0.84 mmol/L) and indirect (5.3 mg/dL; 0.29 mmol/L) bilirubin, alkaline phosphatase (79-260 U/L), and gamma-glutamyltransferase (260 U/L) were observed as biochemical markers of liver damage, with acute and fulminant liver failure the major toxic effects described in the NPS case reports. In vitro laboratory studies and subsequent in vivo NPS exposure studies on rats and mice provide data on potential mechanisms of toxicity. Oxidative stress, plasma membrane stability, and cellular energy changes led to apoptosis and cell death. Experimental studies of human liver microsome incubation with synthetic NPS, with and without specific cytochrome P450 inhibitors, highlighted specific enzyme inhibitions and potential drug-drug interactions leading to hepatotoxicity. Mild to severe hepatotoxic effects following synthetic NPS exposure were described in case reports. In diagnosing the etiology of liver damage, synthetic NPS exposure should be considered as part of the differential diagnosis. Identification of NPS toxicity is important for educating patients on the dangers of NPS consumption and to suggest promising treatments for observed hepatotoxicity.

Biochemical Evaluation of Adansonia Digitata Methanolic Leaf and Stem Bark Extract on Streptozotocin Induced Diabetic Rats

Several herbal preparations are used to treat diabetes; however, their overall biochemical effects other than hypoglycemic effects are scanty. This study therefore was designed to evaluate the effect of methanolic extract of leaves and stem-bark of Adansonia digitata on biochemical indices of streptozotocin-induced diabetic rats. Sixty-three wistar rats were distributed into 9 groups of 7 each. The test animals were intraperitoneally administered with single dose of 50 mg/kg streptozotocin and monitored for 72 hours for development of hyperglycemia. Diabetic rats were treated in 12 h cycles for three weeks with 100 mg/kg, 200 mg/kg and 300 mg/kg of both leaves and stem-bark of Adansonia digitata methanolic extract and metformin (50 mg/kg). Non-diabetic control rats received a lacebo of distilled water. Group 1 served as normal control, group 2 served as diabetic control, while groups 4-9 were diabetic rats treated orally with methanolic leave and stem-bark extracts of Adansonia digitata (100 mg/kg, 200 mg/kg and 300 mg/kg) for 21days. Group 3 animals were diabetic rats treated with anti-diabetic drug (metformin 50 mg/kg). The levels of fasting blood sugar (FBS), electrolytes (Na+, K+, Cl-), Urea and creatinine Triglyceride (TG), Cholesterol (CHOL), thiobarbituric acid reactive substance (TBARS), White Blood Cell (WBC) count, Red Blood Cell (RBC) count, Haemoglobin (HGB), Hematocrit (HCT), Platelet (PLT), Mean Cell Volume (MCV), Mean Cell Haemoglobin (MCH), Mean Cell Haemoglobin Concentration (MCHC), Lymphocyte (LYM), aspartatate aminotransfrease (AST), alanine aminotransferase (ALT), total protein (TP), albumin (ALB), catalase (CAT) and superoxide dismutase (SOD) activities total, total bilirubin (TB), direct bilirubin(DB) and indirect bilirubin (IB) concentrations were assayed. The results indicated that the concentrations of Na+, K+, Cl-, creatinine, urea TBARS, ALT, AST, ALB, CHOL and IB bilirubin were significantly (p&lt;0.05) increased, while the levels of WBC, RBC, HGB, HCT, PLT, LYM, MCV SOD and CAT were reduced in the diabetic control (p&lt;0.05). The Adansonia digitata methanolic leaves and stem-bark extract significantly increased WBC, RBC, HGB, HCT, PLT, MCV, LYM, TP, CAT and SOD activity and reduced the FBS, Na+, K+, Cl-, TBARS, ALT, AST, creatinine, urea and bilirubin concentrations significantly (p&lt;0.05) compared to normal control. However, treatment with metformin showed slight modification in the changes observed compared to Adansonia digitata methanolic leaves and stem-bark extract. MCV and MCHC reduced non-significantly (p&gt;0.05) in the diabetic animals as compared to the normal control and the extract-treated rats, while they increased non- significantly (p&gt;0.05) in the test groups when compared to the diabetic control. Levels of TB, DB, and TG showed non-significant (p&lt;0.05) increase in diabetic control, but treatment with extracts and metformin caused non-significant decrease (p&lt;0.05). Diabetic control exhibited significantly (p&lt;0.05) decreased ALB levels and non-significant TP decrease compared to normal control, while Adansonia digitata extracts and metformin significantly increased ALB and non-significantly increased TP levels compared to diabetic control. The study concluded that Adansonia digitata extracts reversed diabetes-induced oxidative stress in rat hepatocytes, potentially through beta cell regeneration or insulin release stimulation, suggesting their potential for managing diabetic complications.

The effects of astaxanthin supplementation on liver enzyme levels.

According to previous studies, astaxanthin exerts various biological effects due to its anti-inflammatory and antioxidant capabilities; however, its effects on liver enzymes have not yet been well elucidated. Therefore, we conducted a meta-analysis to assess astaxanthin's effects on liver enzymes. A systematic literature search was conducted using scientific databases including PubMed, Scopus, Web of Science, the Cochrane databases, and Google Scholar up to February 2023 to find relevant randomized controlled trials (RCTs) examining the effects of astaxanthin supplementation on alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP). A random-effects model was used for the estimation of the pooled weighted mean difference (WMD). Overall, we included five trials involving 196 subjects. The duration of the intervention was between 4 and 48 weeks, and the dose was between 6 and 12 mg/day. ALT levels increased in the intervention group compared to the control group following astaxanthin supplementation (WMD: 1.92 U/L, 95% CI: 0.16 to 3.68, P=0.03), whereas supplementation with astaxanthin had a non-significant effect on AST (WMD: 0.72 U/L, 95% CI: -0.85 to 2.29, P=0.36), GGT (WMD: 0.48 U/L, 95% CI: -2.71 to 3.67, P=0.76), and ALP levels (WMD: 2.85 U/L, 95% CI: -7.94 to 13.63, P=0.60) compared to the placebo group. Our data showed that astaxanthin supplementation increases ALT concentrations in adults without affecting the levels of other liver enzymes. Further long-term and well-designed RCTs are necessary to assess and confirm these findings.

Autoimmune Hepatitis: A Diagnostic and Therapeutic Overview.

Autoimmune hepatitis is an immune-mediated inflammatory condition of the liver of undetermined cause that affects both sexes, all ages, races, and ethnicities. Its clinical presentation can be very broad, from having an asymptomatic and silent course to presenting as acute hepatitis, cirrhosis, and acute liver failure potentially requiring liver transplantation. The diagnosis is based on histological abnormalities (interface hepatitis), characteristic clinical and laboratory findings (increased aspartate aminotransferase, alanine aminotransferase, and serum IgG concentration), and the presence of one or more characteristic autoantibodies. The large heterogeneity of these clinical, biochemical, and histological findings can sometimes make a timely and proper diagnosis a difficult task. Treatment seeks to achieve remission of the disease and prevent further progression of liver disease. First-line therapy includes high-dose corticosteroids, which are later tapered to decrease side effects, and azathioprine. In the presence of azathioprine intolerance or a poor response to the standard of care, second-line therapy needs to be considered, including mycophenolate mofetil. AIH remains a diagnostic and therapeutic challenge, and a further understanding of the pathophysiological pathways of the disease and the implementation of randomized controlled trials are needed.

Activity and safety of eltrombopag in combination with cyclosporin A as first‑line treatment of adults with severe aplastic anaemia (SOAR): a phase 2, single-arm study

Antithymocyte globulin (ATG)-based immunosuppression is standard in front-line treatment for people with severe aplastic anaemia without a histocompatible donor or who are 40 years or older. However, ATG requires in-hospital administration, is associated with infusion-related toxicities and has limited availability worldwide. In this study, we investigated the activity and safety of an ATG-free regimen of eltrombopag with cyclosporin A as a potential treatment for patients with severe aplastic anaemia who might not have access to or cannot tolerate horse-ATG. SOAR was a multicentre, single-arm phase 2 trial investigating eltrombopag and cyclosporin in adult (≥18 years) patients with severe aplastic anaemia who were treatment-naive and had an Eastern Cooperative Oncology Group performance status of less than 2. Participants were recruited from 20 hospitals in ten countries. Eltrombopag was initiated at 150 mg (100 mg in patients of Asian ethnicity) and cyclosporin at 10 mg/kg per day (adjusted to a trough of 200-400 μg/L) orally from day 1 to 6 months. The primary outcome was an overall haematological response rate by 6 months in the intention-to-treat population. This is the final report of the primary analysis period. The trial was registered with ClinicalTrials.gov, NCT02998645, and has been completed. 54 patients were enrolled between May 11, 2017, and March 23, 2020. 34 (63%) patients were male and 20 (37%) were female. 22 (41%) were Asian, 22 (41%) were White, one (2%) was Native American or Alaska Native, one (2%) was Black or African American, and eight (15%) were other race or ethnicity. 35 patients (65%) completed 6 months of treatment with eltrombopag and cyclosporin and six (11%) completed the cyclosporin tapering period up to month 24. Overall haematological response rate by month 6 of treatment was 46% (25 of 54; 95% CI 33-60). The most reported adverse events were increased serum bilirubin (in 22 patients [41%]), nausea (16 [30%]), increased alanine aminotransferase concentration (12 [22%]), and diarrhoea (12 [22%]). Eight patients died on-treatment, but no deaths were considered related to the treatment. Eltrombopag and cyclosporin was active as front-line treatment of severe aplastic anaemia, with no unexpected safety concerns. This approach might be beneficial where horse-ATG is not available or not tolerated. Novartis Pharmaceuticals.

Toxic effects of clindamycin-hydrochloride in healthy rodents

Background: Systemic administration of clindamycin-hydrochloride (an antibiotic) is mainly associated with gastro-intestinal disturbances and allergic reactions. Little is known of its haematological and biochemical toxicity.&#x0D; Objective: To evaluate the haematological and biochemical changes associated with indiscriminate administration of oral clindamycin-hydrochloride in clinically healthy rodents.&#x0D; Materials and Methods: Twenty Wistar rats (130-189 grams) divided into four groups (A-D) of five rats each were used. Rats in group A (control) were treated with distilled water. Groups B-D received 0.2mL (below normal dose), 0.4mL (normal dose) and 1.0mL (above normal dose) of clindamycin-hydrochloride (75mg/5mL) at 8 hourly intervals, three times daily for 14 days, respectively. Thereafter, blood was collected through both ocular and cardiac puncture into ethylene diamine tetra acetic acid (EDTA) and lithium heparin bottles for evaluation of haematological and biochemical parameters, respectively.&#x0D; Results: Significant (P &lt; 0.05) increases in total white blood cell (WBC) counts and decreases in eosinophil (Eos) counts occurred in clindamycin-treated rats. In addition, significant (P &lt; 0.05) increases in concentrations of Total cholesterol, Triglyceride and High-density lipoprotein, respectively, as well as decreases in concentrations of Albumin, Alanine transaminase and Gamma-glutamyl transpeptidase, respectively also occurred in clindamycin-treated rats.&#x0D; Conclusion: Indiscriminate use of clindamycin-hydrochloride produces adverse haematological and biochemical changes in Wistar rats which may be a reflection of systemic toxicity, allergic reaction as well as liver and kidney dysfunction.

Effect of dietary methionine hydroxy analogue‐free acid (MHA‐FA) supplementation levels on growth performance, blood metabolites and immune responses in broiler chickens

AbstractBackgroundBroiler diets are commonly supplemented by liquid methionine hydroxy analogue‐free acid (MHA‐FA) containing as product with 88% of active substance to meet sulphur amino acid (SAA) requirements.ObjectivesTwo experiments were conducted to assess the effects of different dietary MHA‐FA levels on growth performance, blood metabolites and immune responses in broilers.MethodsIn experiments 1 and 2, 432 and 360 male broilers were fed either a basal corn–soya bean meal diet that met the energy and nutrient requirements with the exception of SAAs or the basal diet supplemented with 5 graded levels of MHA‐FA (+0.9 and +0.8 g/kg), for 1–11 and 11–24‐day ages, respectively. Chicks were vaccinated with inactivated H9N2/Newcastle disease (ND) and live‐ND on days 5 and 11, respectively.ResultsResponses in both experiments had similar tendency at corresponding dietary MHA‐FA levels. By increasing dietary MHA‐FA level, weight gain (WG), feed efficiency (FE), relative breast weight (RBW) and immunity against ND and avian influenza virus inoculation improved with quadratic trend. Blood serum triglyceride, low‐density lipoprotein, alanine aminotransferase and alkaline phosphatase concentration were affected in response to dietary MHA‐FA levels with quadratic trends. By using broken‐line regression analysis, the optimum dietary MHA‐FA levels for optimized WG, FE and RBW during 1–10‐day age were obtained at 2.20, 3.31 and 3.33 g/kg, respectively; based on MHA‐FA content of Met equivalent, the digestible SAA requirements were estimated 0.81%, 0.91% and 0.92%, respectively. Similarly, for the 11–24‐day age period, the optimum dietary MHA‐FA supplementation levels were obtained 1.79, 2.21, 2.41 and 2.53 g/kg, with the digestible SAA requirements estimated 0.75%, 0.79%, 0.80% and 0.81% for optimized WG, FE, RBW and immune responses, respectively.ConclusionsSupplemental levels of MHA‐FA that optimize performance, breast meat and immunity in broilers fed corn–soya bean meal diet, varied from 0.18% to 0.33%, correspond to age and what traits are considered for optimization.

Mediating Role of Liver Dysfunction in the Association between Arsenic Exposure and Diabetes in Chinese Adults: A Nationwide Cross-Sectional Study of China National Human Biomonitoring (CNHBM) 2017-2018.

Inconsistent results have been reported regarding the association between low-to-moderate arsenic (As) exposure and diabetes. The effect of liver dysfunction on As-induced diabetes remains unclear. The cross-sectional study included 10,574 adults from 2017-2018 China National Human Biomonitoring. Urinary total As (TAs) levels were analyzed as markers of As exposure. Generalized linear mixed models and restricted cubic splines models were used to examine the relationships among TAs levels, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations, and diabetes prevalence. Mediating analysis was performed to assess whether liver dysfunction mediated the association between TAs and diabetes. Overall, the OR (95% CI) of diabetes in participants in the second, third, and fourth quartiles of TAs were 1.08 (0.88, 1.33), 1.17 (0.94, 1.45), and 1.52 (1.22, 1.90), respectively, in the fully adjusted models compared with those in the lowest quartile. Serum ALT was positively associated with TAs and diabetes. Additionally, mediation analyses showed that ALT mediated 4.32% of the association between TAs and diabetes in the overall population and 8.86% in the population without alcohol consumption in the past year. This study suggested that alleviating the hepatotoxicity of As could have implications for both diabetes and liver disease.

Activity of enzymes in the follicular fluid and outcome of in vitro fertilization.

Defining certain parameters of the oocyte microenvironment that can be simply and quickly detected and that enable differentiation of oocytes that have better or worse quality could potentially increase the efficacy of the in vitro fertilization (IVF) method. Follicular fluid represents the microenvironment for the development of oocytes during different stages of maturation. Enzymes present in the follicular fluid may affect the quality of oocytes. There are inconsistencies in the literature concerning enzyme concentration in follicular fluid. The main aim of this study was to examine whether the concentration of enzymes aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase, and lactate dehydrogenase in follicular fluid can influence the outcome of IVF. The study included 120 patients who were involved in the process of IVF. We used the follicular fluid obtained after follicular aspiration in the ovaries as biological material for the analysis. The values of enzymes LDL (method-kinetic UV test), aspartate aminotransferase (method-kinetic UV test), ALT (method-kinetic UV test) and alkaline phosphatase (method-colorimetric kinetic test) in the follicular fluid were determined on the analyzer АU 680, Becman Coulter. The criteria of the Istanbul consensus of clinical embryologists were used for the embryo assessment. The software package SPSS 20 was used for the statistical processing of data. The results of follicular fluid sample analysis showed a correlation between ALT concentration in the follicular fluid and IVF outcome. Based on our results, we can conclude that ALT concentration affects the outcome of IVF.

Indexing serum and mucous biochemical parameters of endangered Chinese sturgeon Acipenser sinensis with implications for health assessment.

The Chinese sturgeon (Acipenser sinensis) is a critically endangered aquatic fish. Health monitoring and welfare assessments are critical for the conservation of Chinese sturgeon. In this study, biochemical parameters of serum and skin mucus in Chinese sturgeon were examined to evaluate the potential biomarkers. Serum and mucous samples were obtained from Chinese sturgeon, and the levels of total protein (TP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatine kinase (CK), lactic acid (LD), acid phosphatase (ACP), lysozyme (LYZ), glucose (GLU), and cortisol were determined. The concentrations of ALT, AST, cortisol, and LYZ were significantly higher in the mucous group than those in the serum group (p < 0.05). In addition, the concentrations of ALP, ACP, LD, LDH, CK, and TP were significantly higher level in the serum group than those in the mucous group (p < 0.05). Moreover, the correlations between serum and mucous biochemical parameters were established. Statistical analysis showed a positive correlation between serum and skin mucous markers (ACP, cortisol, and LYZ). AST versus ALT in serum and mucus showed a significant positive correlation (p < 0.01). A significant positive correlation was found between cortisol and CK in mucus (p < 0.01). Moreover, LD versus LDH in serum showed a significant but weak positive correlation (p < 0.01). Principal component analysis revealed a complete separation between the serum and mucous groups, with the biomarkers that contributed the most being ALP, TP, ALT, and AST. This study provides baseline data and reference intervals for serum and mucous biochemical parameters in presumably healthy Chinese sturgeons. The current study has important implications for the development of conservation strategies and the conservation status of critically endangered species.

Causal associations between liver enzymes and diabetic microvascular complications: A univariable and multivariable Mendelian randomization.

Observational studies show that liver enzymes are diabetes risk factors. However, previous observational investigations on the relationship between liver enzymes and diabetic microvascular complications produced contradictory results. The purpose of this research is to examine the independent causal effects of liver enzymes on diabetic microvascular complications. Univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) were utilized to disentangle the causal effects. The genome-wide association study (GWAS) summary-level statistics were collected from the UK biobank and the FinnGen consortium. Single nucleotide polymorphisms (SNPs) were selected as genetic instruments with genome-wide significance (p < 5 ×10-8). Five UVMR approaches, including inverse variance weighted (IVW), Bayesian weighted Mendelian randomization, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO), weighted median, and MR-Egger, and three MVMR approaches, including the extended versions of IVW, MR-Egger, and the Q-minimization methods, were performed to evaluate the causal effects. The robustness of the MR results was further confirmed using several sensitivity analyses. UVMR revealed that a genetically predisposed per standard deviation increase in serum alanine aminotransferase (ALT) level increased the risk of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) (IVW OR = 1.489, 95% CI = 1.206-1.772, p = 0.006). Likewise, serum aspartate aminotransferase (AST) levels showed similar results (IVW OR = 1.376, 95% CI = 1.115-1.638, p = 0.017). Furthermore, these effects were consistent after controlling for glycemia and blood pressure using MVMR analysis. Additionally, sensitivity analyses further strengthened the causality. However, no significant associations were found between alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and diabetic microvascular complications. Robust evidence was demonstrated for an independent causal effect of serum ALT or AST concentration on the risk of DR in T2DM. Further investigations are necessary to elucidate the potential biological mechanisms and confirm their clinical significance for early prevention and intervention.

The Effect of Yucca schidigera Extract on Serum Metabolites of Angus Crossbreed Steers with Metabolomics.

This study was conducted to explore the potential effect of Yucca schidigera extract (YSE) on the metabolism of beef cattle. Thirty Angus crossbreed steers were selected, with an initial mean body weight of 506.6 ± 33.3 kg, and assigned to two treatments: a diet with no additives (CON group) and a diet supplemented with 1.75 g/kg of YSE (YSE group) (on a dry matter basis). The experiment lasted for 104 days, with 14 days for adaptation. The results showed that adding YSE could significantly improve the average daily gain (ADG) from 1 to 59 d (15.38%) (p = 0.01) and 1 to 90 d (11.38%) (p < 0.01), as well as dry matter digestibility (DMD) (0.84%) (p < 0.05). The contents of alanine aminotransferase, aspartate aminotransferase, and bilirubin and the total antioxidant capacity were increased and blood urea was reduced in the YSE group, compared to the CON group (p < 0.05). Both the glycerophospholipids and bile acids, including phosphocholine, glycerophosphocholine, PC(15:0/18:2(9Z,12Z)), PE(18:0/20:3(5Z,8Z,11Z)), PE(18:3(6Z,9Z,12Z)/P-18:0), LysoPC(15:0), LysoPC(17:0), LysoPC(18:0), LysoPC(20:5(5Z,8Z,11Z,14Z,17Z)), deoxycholic acid, glycocholic acid, and cholic acid, were upregulated by the addition of YSE. In summary, YSE may improve the ADG by increasing the blood total antioxidant capacity and glycerophospholipid synthesis, maintaining steers under a healthy status that is beneficial for growth. Furthermore, YSE may also increase the expression of bile acid synthesis, thereby promoting DMD, which, in turn, offers more nutrients available for growth.