Alanine Aminotransferase Levels Research Articles

Impact of one-anastomosis gastric bypass and laparoscopic sleeve gastrectomy on metabolic parameters in morbidly obese patients: A comparative review.

Objective: To compare one-anastomosis gastric bypass and laparoscopic sleeve gastrectomy in morbidly obese patients in terms of frequency of dyslipidemia, mean AST, mean ALT, mean HbA1C and mean FPG. Study Design: Randomized Controlled Trial Setting: Department of General Surgery, Allied Hospital, Faisalabad. Period: October 20, 2022, to June 20, 2023, Methods: Morbidly obese individuals were randomly assigned to either undergo laparoscopic sleeve gastrectomy (Group A) or one-anastomosis gastric bypass (Group B). The study, led by a consultant with 3 years of post-fellowship experience, conducted comprehensive patient assessments, including BMI calculations and metabolic profiling. Monthly follow-ups continued until the 6th month, after which lipid profiles, alanine transaminase (ALT), aspartate transaminase (AST), hemoglobin A1C (HbA1C) and fasting plasma glucose (FPG), results were obtained from the hospital pathology lab. The comparative analysis revealed superior outcomes in Group B, the one-anastomosis gastric bypass cohort, as compared to Group A (laparoscopic sleeve gastrectomy), spanning multiple parameters. Results: The mean FPG in Group A was 5.52±0.26, compared to 5.56±0.25 in Group B. Mean HbA1c was 6.65±0.24 in Group A and 6.26±0.19 in Group B. AST levels were comparable, with 24.13±3.31 in Group A and 24.23±3.48 in Group B, yielding a p-value of 0.896. Similarly, ALT levels showed no significant difference between the groups (24.55±3.46 in Group A and 23.92±3.35 in Group B, p-value=0.414). Conclusion: One-anastomosis gastric bypass demonstrated superior efficacy over laparoscopic sleeve gastrectomy in morbidly obese patients, showcasing favorable outcomes in terms of dyslipidemia, AST, ALT, HbA1C, and FPG.

Efficacy and tolerability of oral semaglutide in Japanese patients with type 2 diabetes mellitus: Analysis report from diabetes specialist clinics.

Glucagon-like peptide 1 receptor agonists (GLP1Ras) have emerged as pivotal agents in diabetes management and organ protection. However, their use is limited due to the necessity for injectable administration. The advent of the first oral GLP1Ra (oral semaglutide) in Japan since 2021 is expected to expand its usage. The aim of this study is to survey the efficacy and tolerability of oral semaglutide in clinical practice. We retrospectively analyzed 120 outpatients diagnosed with type 2 diabetes mellitus who had received oral semaglutide for >6 months. Changes in clinical parameters during oral semaglutide treatment from baseline to 12 months were analyzed. The inverse probability weighting method using the propensity score was used to evaluate the differences in clinical parameters at 6 months after treatment, based on the patients' obesity levels. Body weight (BW), glycated hemoglobin A1c (HbA1c), and alanine aminotransferase (ALT) levels at baseline decreased significantly after treatment compared with those at 12 months (P < 0.001, P < 0.001, and P = 0.03, respectively). The patients were divided into two groups using a cutoff baseline body mass index (BMI) of 30.3 kg/m2. Although no significant difference was observed, changes in body weight and HbA1c indicated a potentially greater decrease in the BMI ≧ 30.3 group than that in the BMI < 30.3 group (P = 0.07 and 0.13, respectively). Among 206 registered patients, 25 (12.1%) discontinued oral-semaglutide treatment owing to adverse effects, including gastrointestinal symptoms. Oral semaglutide treatment demonstrates efficacy and tolerability for managing type 2 diabetes mellitus in Japan. Significant improvements in metabolic factors induced by oral semaglutide are anticipated, particularly in obese patients.

Risk and timing of isotretinoin-related laboratory disturbances: a population-based study.

Uncertainty surrounds the optimal routine laboratory monitoring in acne patients treated with isotretinoin. Our aim was to evaluate the risk of mild and severe laboratory abnormalities in patients with acne starting isotretinoin versus oral antibiotic treatment. A global population-based retrospective cohort study assigned two groups of patients with acne-prescribed isotretinoin (n = 79,012) and oral antibiotics (n = 79,012). Comprehensive propensity-score matching was conducted. Compared to acne patients treated with oral antibiotics, those under isotretinoin demonstrated an increased risk of grade ≥3 hypertriglyceridemia (hazard ratio [HR], 7.85; 95% confidence interval [CI], 5.58-11.05; P < 0.001) and grade ≥3 elevated aspartate transaminase (AST) levels (HR, 1.45; 95% CI, 1.13-1.85; P = 0.003) within the initial 3 months of treatment. The absolute risk of these abnormalities among isotretinoin initiators was 0.4% and 0.2%, respectively. The risk difference of these findings was clinically marginal: 3 and 1 additional cases per 1,000 patients starting isotretinoin, respectively. There was no significant risk of grade ≥3 impairment in cholesterol, alanine transaminase, gamma-glutamyl transferase, or creatinine levels under isotretinoin. Most laboratory abnormalities were documented 1-3 months after drug initiation in time-stratified analysis. Isotretinoin is associated with a clinically marginal increased risk of severe hypertriglyceridemia and hypertransaminasemia. Routine blood testing should be performed 1-3 months after commencing therapy.

Therapeutic Potential of Silymarin in Mitigating Paclitaxel-Induced Hepatotoxicity and Nephrotoxicity: Insights into Oxidative Stress, Inflammation, and Apoptosis in Rats.

Paclitaxel (PAX) is a widely used chemotherapy drug for various cancer types but often induces significant toxicity in multiple organ systems. Silymarin (SIL), a natural flavonoid, has shown therapeutic potential due to its multiple benefits. To evaluate the therapeutic efficacy of SIL in mitigating liver and kidney damage induced by PAX in rats, focusing on oxidative stress, inflammation, and apoptosis pathways. Experimental animal model. The study included 28 male Wistar rats aged 12-14 weeks weighing 270-300 g. The rats were divided into four groups: control, SIL, PAX, and PAX + SIL, with seven in each group. The rats received intraperitoneal (i.p.) injections at a dose of 2 mg per kilogram of body weight of PAX for 5 successive days, followed by oral gavage with 200 mg/kg body mass of SIL for 10 uninterrupted days. We examined the effect of SIL on specific serum biochemical parameters using an autoanalyzer and rat-specific kits. The spectrophotometric methods was used to investigate oxidative stress indicators in kidney and liver tissues. Aquaporin-2 (AQP-2), B-cell lymphoma-2 (Bcl-2), cysteine aspartate-specific protease-3 (caspase-3), interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), and streptavidin-biotin staining were used to assess immunoreactivity in PAX-induced liver and kidney injury models. SIL treatment significantly reduced serum levels of alanine aminotransferase, aspartate aminotransferase, creatinine, urea, and C-reactive protein, indicating its effectiveness in treating PAX-induced liver and kidney injury. SIL treatment significantly reduced oxidative stress by increasing essential antioxidant parameters, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione. It also reduced malondialdehyde levels in liver and kidney tissues of SIL-PAX groups (p < 0.05). SIL administration reduced NF-κB, caspase-3, and IL-6 expression while increasing Bcl-2 and AQP2 levels in liver and kidney tissues of rats treated with SIL and PAX (p < 0.05). Our findings indicate the potential of SIL to alleviate PAX-induced liver and kidney damage in rats by reducing oxidative stress, inflammation, and apoptotic processes.

Effects of micro/nanoplastics on oxidative damage and serum biochemical parameters in rats and mice: a meta-analysis.

Micro/nanoplastics (MNPs) are emerging as environmental pollutants with potential threats to human health. The accumulation of MNPs in the body can cause oxidative stress and increase the risk of cardiovascular disease (CVD). With the aim to systematically evaluate the extent of MNPs-induced oxidative damage and serum biochemical parameters in rats and mice, a total of 36 eligible articles were included in this meta-analysis study. The results reported that MNPs can significantly increase the levels of oxidants such as reactive oxygen species (ROS) and malondialdehyde (MDA) (P < 0.05), and resulted in notable increase in serum biochemical parameters including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P < 0.05). Conversely, MNPs significantly reduced levels of antioxidants such as superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx) and catalase (CAT) (P < 0.05). Subgroup analysis revealed that smaller MNPs with oral administration and prolonged treatment, were associated with more pronounced oxidative stress and enhanced serum biochemical parameters alteration. In addition, after affected by MNPs, the levels of ALT and AST in liver group (SMD = 2.26, 95% CI = [1.59, 2.94] and SMD = 3.10, 95% CI = [1.25, 4.94]) were higher than those in other organs. These comprehensive results provide a scientific foundation for devising strategies to prevent MNPs-induced damage, contributing to solution of this environmental and health challenge.

Relationship between ocular manifestations, laboratory findings, echocardiographic findings, and intravenous immunoglobulin resistance in Kawasaki disease.

This study investigates the incidence of ocular involvement in Kawasaki disease (KD) and evaluates the relationship between ocular manifestations, laboratory findings, echocardiographic findings, and intravenous immunoglobulin (IVIG) resistance. We conducted a cross-sectional study with 58 KD patients from June 2021 to March 2023. For all patients, a complete ophthalmologic examination and echocardiography were performed in the acute phase before starting the treatment. We analyzed the age, sex, mean of white blood cell (WBC) count, platelet count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), echocardiographic findings and IVIG responses for all patients and compared the group with ocular involvement with the group without involvement. The incidence of bilateral acute conjunctivitis was 70.7%, while that of acute uveitis was 30%. Patients with uveitis had significantly higher rates of Coronary artery dilatation and IVIG resistance, as well as higher mean levels of WBC, platelet, and CRP compared to those without uveitis. (P < 0.05). Additionally, the age of patients with uveitis involvement was lower than those without involvement. No significant relationships existed between ESR, AST, or ALT values and uveitis (P > 0.05). Furthermore, no significant correlations existed between any examined items and acute bilateral conjunctivitis. Uveitis in KD is significantly associated with coronary artery dilatation, IVIG resistance, higher WBC count, platelet count, and CRP level.

Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patient with chronic hepatitis B.

Our study evaluated the outcomes of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in patients with chronic hepatitis B (CHB). We assessed viral and biochemical responses as well as changes in the estimated glomerular filtration rate (eGFR) and bone mineral density (BMD). This retrospective multicenter study included CHB patients who achieved virologic response (VR) (HBV DNA<20IU/mL) while on TDF and were subsequently switched to TAF between April 2018 and October 2021. This study included 309 patients with a median age of 59years, and 42.1% were male. The mean duration of TDF and TAF administration were 54.0 and 37.5months, respectively. All patients maintained VR after switching to TAF. Alanine aminotransferase (ALT) normalization rate significantly increased 6months after switching (74.8%-83.5%; P=0.008). Adjusted eGFR significantly improved at 6months (+5.55±10.52mL/min/1.73m2; P<0.001) and 12months (+6.02±10.70mL/min/1.73m2; P<0.001) after switching. In the subgroup of patients with renal impairment (eGFR<60mL/min/1.73m2), significant improvement in renal function was observed at 6months (+0.6±10.5mL/min/1.73m2; P<0.001) and 12months (+1.0±10.7mL/min/1.73m2; P<0.001) after switching to TAF. In patients with osteoporosis (n=182), switching to TAF resulted in significant improvement in spine and hip BMD at 12months, with increases of 9.7% (95% CI: 7.0-12.5) and 9.4% (95% CI: 7.0-11.8), respectively. In this real-world study, switching to TAF was effective and safe in patients, with notable improvements in ALT levels, renal function, and BMD.

A genome-first approach to variants in MLXIPL and their association with hepatic steatosis and plasma lipids.

Common variants of the max-like protein X (MLX)-interacting protein-like (MLXIPL) gene, encoding the transcription factor carbohydrate-responsive element-binding protein, have been shown to be associated with plasma triglyceride levels. However, the role of these variants in steatotic liver disease (SLD) is unclear. We used a genome-first approach to analyze a variety of metabolic phenotypes and clinical outcomes associated with a common missense variant in MLXIPL, Gln241His, in 2 large biobanks: the UK Biobank and the Penn Medicine Biobank. Carriers of MLXIPL Gln241His were associated with significantly lower serum levels of triglycerides, apolipoprotein-B, gamma-glutamyl transferase, and alkaline phosphatase. Additionally, MLXIPL Gln241His carriers were associated with significantly higher serum levels of HDL cholesterol and alanine aminotransferase. Carriers homozygous for MLXIPL Gln241His showed a higher risk of SLD in 2 unrelated cohorts. Carriers of MLXIPL Gln241His were especially more likely to be diagnosed with SLD if they were female, obese, and/or also carried the PNPLA3 I148M variant. Furthermore, the heterozygous carriage of MLXIPL Gln241His was associated with significantly higher all-cause, liver-related, and cardiovascular mortality rates. Nuclear magnetic resonance metabolomics data indicated that carriage of MLXIPL Gln241His was significantly associated with lower serum levels of VLDL and increased serum levels of HDL cholesterol. Analyses of the MLXIPL Gln241His polymorphism showed a significant association with a higher risk of SLD diagnosis and elevated serum alanine aminotransferase as well as significantly lower serum triglycerides and apolipoprotein-B levels. MLXIPL might, therefore, be a potential pharmacological target for the treatment of SLD and hyperlipidemia, notably for patients at risk. More mechanistic studies are needed to better understand the role of MLXIPL Gln241His on lipid metabolism and steatosis development.

Cytokine storm modulation using cholecalciferol and low dose gamma radiation in Escherichia coli infected mice.

This work investigates the efficiency of cholecalciferol and low dose gamma radiation in modulating cytokine storm through their impact on inflammatory and anti-inflammatory cytokine and protecting against lung and liver injuries. Male Swiss albino mice were exposed to 0.2 Gy gamma radiation/week for four consecutive weeks then injected intraperitoneally (i.p) with a single dose of 8.3 × 106 CFU Escherichia coli/g b.w. then injected i.p. with 1.0 mg/kg cholecalciferol (Vit D3) for 7 days starting 4 h after E. coli injection. The results revealed that Cholecalciferol and low dose gamma radiation caused significant depletion in the severity of E. coli infection (colony forming unit per milliliter), log10 of E. coli, Tumor necrosis factor alpha, Interleukin 6, VEGF, alanine aminotransferase, and aspartate aminotransferase levels and significant elevation in IL-10, IL-4, and HO-1. Immunohistochemical analysis of caspase-3 expression in lung tissue section showed low caspase-3 expression in cholecalciferol and low dose gamma radiation treated group. Histopathological examinations were performed in both lung and liver tissues which also emphasis the biochemical findings. Our results exhibit the importance of cholecalciferol and low dose gamma radiation in improving liver function and providing anti-inflammatory response in diseases causing cytokine storm.

Potential utility of l-carnitine for preventing liver tumors derived from metabolic dysfunction-associated steatohepatitis.

Recent reports have unveiled the potential utility of l-carnitine to alleviate metabolic dysfunction-associated steatohepatitis (MASH) by enhancing mitochondrial metabolic function. However, its efficacy at preventing the development of HCC has not been assessed fully. l-carnitine (2g/d) was administered to 11 patients with MASH for 10 weeks, and blood liver function tests were performed. Five patients received a serial liver biopsy, and liver histology and hepatic gene expression were evaluated using this tissue. An atherogenic plus high-fat diet MASH mouse model received long-term l-carnitine administration, and liver histology and liver tumor development were evaluated. Ten-week l-carnitine administration significantly improved serum alanine transaminase and aspartate transaminase levels along with a histological improvement in the NAFLD activity score, while steatosis and fibrosis were not improved. Gene expression profiling revealed a significant improvement in the inflammation and profibrotic gene signature as well as the recovery of lipid metabolism. Long-term l-carnitine administration to atherogenic plus high-fat diet MASH mice substantially improved liver histology (inflammation, steatosis, and fibrosis) and significantly reduced the incidence of liver tumors. l-carnitine directly reduced the expression of the MASH-associated and stress-induced transcriptional factor early growth response 1. Early growth response 1 activated the promoter activity of neural precursor cell expressed, developmentally downregulated protein 9 (NEDD9), an oncogenic protein. Thus, l-carnitine reduced the activation of the NEDD9, focal adhesion kinase 1, and AKT oncogenic signaling pathway. Short-term l-carnitine administration ameliorated MASH through its anti-inflammatory effects. Long-term l-carnitine administration potentially improved the steatosis and fibrosis of MASH and may eventually reduce the risk of HCC.

Stability and transepithelial transport of oligopeptide (KRQKYD) with hepatocyte-protective activity from Jinhua ham in human intestinal Caco-2 monolayer cells

The study evaluated the stability of an oligopeptide (Lys-Arg-Gln-Lys-Tyr-Asp, KRQKYD) and its transport mechanism by simulating gastrointestinal digestion and a model of human intestinal Caco-2 monolayer cells in vitro. In this study, the effects of environmental factors (temperature, pH and NaCl concentration) and simulated gastrointestinal digestion on the stability of KRQKYD were evaluated by indicators of the levels of alanine transaminase (ALT), aspartate transaminase (AST) and malondialdehyde (MDA) in an alcohol-induced hepatocyte injury model. The results showed that KRQKYD still maintained satisfactory hepatocyte-protective activity after treatment with different temperatures (20−80 °C), pH (3.0−9.0), NaCl concentration (1 %−7 %) and simulated gastrointestinal digestion, which indicated that KRQKYD showed good stability to environmental factors and simulated gastrointestinal digestion. Furthermore, the intact KRQKYD could be absorbed in a model of Caco-2 monolayer cells with a Papp value of (9.70 ± 0.53) × 10−7 cm/s. Pretreatment with an energy inhibitor (sodium azide), a competitive peptide transporter inhibitor (Gly-Pro) and a transcytosis inhibitor wortmannin did not decrease the level of transepithelial KRQKYD transport, indicating that the transport mechanism of KRQKYD was not associated with energy dependent, vector mediated and endocytosis. The tight junction disruptor cytochalasin D significantly increased the level of transepithelial KRQKYD transport (P < 0.05), suggesting that intact KRQKYD was absorbed by paracellular transport.

Genetic and Lifestyle Risk Factors of Metabolic Dysfunction-Associated Fatty Liver Disease and Its Relationship with Premature Coronary Artery Disease: A Study on the Pars Cohort.

The main objective of this study is to identify the risk factors of metabolic dysfunction-associated fatty liver disease (MAFLD) in coronary artery disease (CAD) patients. The present retrospective cohort study is part of the Pars Cohort Study (PCS). The participants were categorized as having MAFLD or not. The pattern of independent variables in patients was compared with those who did not have MAFLD. All variables were retained in the multivariable logistic regression model. Totally, 1862 participants with CAD were enrolled in this study. MAFLD was diagnosed in 647 (40.1%) participants. Gender, diabetes, hypertension, tobacco, opium, alcohol, age, weight, waist circumference, cholesterol, HDL, triglyceride, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were significantly different in MAFLD and non-MAFLD patients. Also, the results of multivariable logistic regression show male gender (OR=0.651, 95% CI: 0.470‒0.902, P value=0.01) and opium consumption (OR=0.563, 95% CI: 0.328‒0.968, P value<0.001) to be negative risk factors of MAFLD occurrence in CAD patients. Having diabetes (OR=2.414, 95% CI: 1.740-3.349, P value<0.001), high waist circumference (OR=1.078, 95% CI: 1.055‒1.102, P value<0.01), high triglyceride (OR=1.005, 95% CI: 1.001‒1.008, P value=0.006), and high ALT (OR=1.039, 95% CI: 1.026‒1.051, P value<0.01) were positive risk factors of MAFLD in CAD patients. Our study found that consuming opium decreases the likelihood of MAFLD in CAD patients, since these patients have decreased appetite and lower body mass index (BMI). On the other hand, female gender, having diabetes, high waist circumference, high triglyceride levels, and high ALT levels increase the probability of MAFLD in CAD patients.

MARC1 in MASLD: Modulation of lipid accumulation in human hepatocytes and adipocytes.

Mutations in the gene MTARC1 (mitochondrial amidoxime-reducing component 1) protect carriers from metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. MTARC1 encodes the mARC1 enzyme, which is localized to the mitochondria and has no known MASH-relevant molecular function. Our studies aimed to expand on the published human genetic mARC1 data and to observe the molecular effects of mARC1 modulation in preclinical MASH models. We identified a novel human structural variant deletion in MTARC1, which is associated with various biomarkers of liver health, including alanine aminotransferase levels. Phenome-wide Mendelian Randomization analyses additionally identified novel putatively causal associations between MTARC1 expression, and esophageal varices and cardiorespiratory traits. We observed that protective MTARC1 variants decreased protein accumulation in in vitro overexpression systems and used genetic tools to study mARC1 depletion in relevant human and mouse systems. Hepatocyte mARC1 knockdown in murine MASH models reduced body weight, liver steatosis, oxidative stress, cell death, and fibrogenesis markers. mARC1 siRNA treatment and overexpression modulated lipid accumulation and cell death consistently in primary human hepatocytes, hepatocyte cell lines, and primary human adipocytes. mARC1 depletion affected the accumulation of distinct lipid species and the expression of inflammatory and mitochondrial pathway genes/proteins in both in vitro and in vivo models. Depleting hepatocyte mARC1 improved metabolic dysfunction-associated steatotic liver disease-related outcomes. Given the functional role of mARC1 in human adipocyte lipid accumulation, systemic targeting of mARC1 should be considered when designing mARC1 therapies. Our data point to plasma lipid biomarkers predictive of mARC1 abundance, such as Ceramide 22:1. We propose future areas of study to describe the precise molecular function of mARC1, including lipid trafficking and subcellular location within or around the mitochondria and endoplasmic reticulum.

Virgin coconut oil mitigates the hepatotoxic effect of atrazine and diabetes on liver enzymes in male Wistar rats

To assess the hepatoprotective action of Virgin Coconut Oil(VCO) in atrazine administered rats. Adult male Wistar rats weighing 180-200 g body weight were separated into two major experimental groups. 35 rats in the test group were divided into five sub-groups of 7rats: Subgroup (SG)1,2 and 3 received 10 ml/kg body weight of distilled water, 10 ml/kg VCO and 123 mg/kg Atrazine (ATZ) respectively, SG 4 was diabetic control group and SG 5 was diabetic group treated with 10 ml/kg of VCO for 2weeks, after which the animals were sacrificed and blood collected for analysis. 35 rats for the recovery group were also divided into 5 subgroups of 7 rats; SG1 and 2 received 10 ml/kg body weight of distilled water and 10 ml/kg of VCO, SG 3, 4 and 5 received 123 mg/kg of ATZ for 2 weeks. After the first 2 weeks, SG 1,2,3 continued the initial treatment while the rats in SG4 and SG5 were fed with 10 ml/kg of VCO and10 ml/kg of distilled water respectively. After 2 weeks, all the animals were sacrificed and blood collected for analysis. We observed a significant increase in the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels of the diabetes control and diabetes treated with VCO groups compared to the normal control. In the groups administered with atrazine, the result showed elevations in serum AST and ALT. With VCO,a significant decrease in ALT levels when compared to the ATZ continued group was observed, further potentiating the hepatoprotective ability of VCO.

Peroxisome proliferator-activated receptors gama ameliorates liver fibrosis in non-alcoholic fatty liver disease by inhibiting TGF-β/Smad signaling activation

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a chronic condition characterized by a progressive decline in liver function, leading to disruptions in liver integrity and metabolic function, resulting in lipid deposition and excessive accumulation of extracellular matrix (ECM). The pathogenesis of NAFLD is complex and not yet fully understood, contributing to the absence of specific therapeutic strategies. Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor pivotal in regulating lipid and glucose metabolism. However, the impacts of PPARγ on NAFLD remains insufficiently explored. Thus, this study aimed to investigate the role of PPARγ in NAFLD and its underlying molecular mechanisms. Methods Chemical detection kits were utilized to quantify collagen content, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) level variations. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess alterations in extracellular matrix-related genes and inflammatory response genes in liver tissue and HepG2 cells, while western blotting was conducted to analyze the levels of both PPARγ and the TGF-β/Smad signaling pathway. Results Our findings unveiled significantly reduced PPARγ expression in a rat model of NAFLD, leading to subsequent activation of the TGF-β/Smad signaling pathway. Furthermore, PPARγ activation effectively mitigated NAFLD progression by inhibiting inflammation and fibrosis-related gene expression and collagen production. On a cellular level, PPARγ activation was found to inhibit the expression of extracellular matrix-related genes such as matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9), along with inflammatory response genes interleukin (IL)-1β and IL-6. Additionally, PPARγ activation led to a significant decrease in the levels of ALT and AST. At the molecular level, PPARγ notably down-regulated the TGF-β/Smad signaling pathway, which is known to promote liver fibrosis. Conclusion These groundbreaking findings underscore PPARγ activation as a promising therapeutic approach to delay NAFLD progression by targeting the TGF-β/Smad signaling pathway in hepatic cells. This highlights the potential of PPARγ as a promising therapeutic target for NAFLD management in clinical settings.

Presence of eimerias in weaned alpacas and control alternative without causing liver damage

Considering eimeriosisin alpacasitis a fatal disease, raising the aim of providing an alternative to prophylactic control in alpacas. 30 weaned alpacas from CICAS “La Raya” of Cusco in August 2022were evaluated. These have been distributed in 3 groups of 10 alpacas. Toltrazuril was administered: group1(G1) 15 mg/kpv, group2 (G2) 22.5 mg/kpv and group3 (G3) control. Qualitative coproparasitological analysis of concentration by flotation. And quantitative analysis has been carried out using the modified McMaster method pre and post treatment. Possible liver damage was evidenced by serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). As results, 93.33% of weaned alpacas have presented eimeriosis. It has been shown a higher prevalence of E. macusaniensis(63.33%). In addition, 22.5 mg/kpv Toltrazuril partially controled E. macusaniensis. While 15 and 22.5 mg/kpv effectively control E. lamae. Furthermore, serum AST and ALT levels were 5.7 IU/L and 195.8 IU/L,respectively, post treatment with 22.5 mg/kpv Toltrazuril. In conclusion, Toltrazuril manages to control pathogenic eimeriae in alpacas, partially E. macusaniensis; buteffectively small eimeriae such as E. lamae. These doses do not alter liver function in weaned alpacas.

The effect of letrozole on liver function and some biochemical parameters in rats

Letrozole (LTZ), is an aromatase inhibitor, that has been widely used in a variety of diseases such as polycystic ovary syndrome, endometriosis, and breast cancer. LTZ is received via the oral route and metabolized in the liver. Therefore, LTZ may have toxic effects like other drugs metabolized in the liver. Based on this, our study aimed to investigate the effect of LTZ on liver function and biochemical parameters. For this purpose, 16 Wistar albino female rats were divided into two groups (n=8): Control and LTZ respectively. The rats in the letrozole group were administered with 2 mL/kg LTZ by oral gavage once a day for 21 days. The Control group received the vehicle once a day for 21 days. Blood samples were collected on the 22nd day of the experiment. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), albumin (ALB), alkaline phosphatase (ALP), direct bilirubin and total bilirubin were measured. Biochemical analysis indicated that ALT, AST, LDH, ALP, and total bilirubin levels were significantly higher in the LTZ administrated group compared to the Control. ALB levels decreased in the LTZ group. In conclusion, it was determined that LTZ has toxic and detrimental effects on the liver. We suggested that long-term LTZ administrated patients should be under control against liver damage and may have liver supporting adjuvant therapies for robust liver functions.

Differential Effects of HDAC6 Inhibition Versus Knockout During Hepatic Ischemia-reperfusion Injury Highlight Importance of HDAC6 C-terminal Zinc-finger Ubiquitin-binding Domain.

Ischemia-reperfusion injury (IRI) causes significant morbidity in liver transplantation among other medical conditions. IRI following liver transplantation contributes to poor outcomes and early graft loss. Histone/protein deacetylases (HDACs) regulate diverse cellular processes, play a role in mediating tissue responses to IRI, and may represent a novel therapeutic target in preventing IRI in liver transplantation. Using a previously described standardized model of murine liver warm IRI, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were assessed at 24 and 48 h after reperfusion to determine the effect of different HDAC inhibitors. Broad HDAC inhibition with trichostatin-A (TSA) was protective against hepatocellular damage (P < 0.01 for AST and P < 0.05 for ALT). Although HDAC class I inhibition with MS-275 provided statistically insignificant benefit, tubastatin-A (TubA), an HDAC6 inhibitor with additional activity against HDAC10, provided significant protection against liver IRI (P < 0.01 for AST and P < 0.001 for ALT). Surprisingly genetic deletion of HDAC6 or -10 did not replicate the protective effects of HDAC6 inhibition with TubA, whereas treatment with an HDAC6 BUZ-domain inhibitor, LakZnFD, eliminated the protective effect of TubA treatment in liver ischemia (P < 0.01 for AST and P < 0.01 for ALT). Our findings suggest TubA, a class IIb HDAC inhibitor, can mitigate hepatic IRI in a manner distinct from previously described class I HDAC inhibition and requires the HDAC6 BUZ-domain activity. Our data corroborate previous findings that HDAC targets for therapeutic intervention of IRI may be tissue-specific, and identify HDAC6 inhibition as a possible target in the treatment of liver IRI.

Comparative impact of replacing fish meal with azolla on growth, water quality, and physiology of red tilapia fingerlings at varying salinities.

A 210-day experiment to assess the efficacy of substituting azolla plant powder at levels of 0, 20, 40, and 60% for fish meal on red tilapia fingerlings (RTF, initial weight of 18.23 ± 0.12 g) performance under salinity levels of 5, 18, and 28ppt. Among the various conditions, RTF-fed 20% azolla at 28 and 5ppt salinity showcased the highest specific growth rate (SGR), whereas the lowest SGR was observed in fish-fed 60% azolla at 5ppt salinity. Upon azolla incorporation, noteworthy elevations in phytoplankton, zooplankton, dissolved oxygen (DO), pH, NH3, and NO3 were noted and conversely, azolla introduction led to decreased NH4 and NO2 concentrations in all salinity levels. Further, a significant (p < 0.05) interaction between azolla levels and water salinity (S×A) significantly impacted the hematological parameters of RTF. The highest levels of superoxide dismutase (SOD), catalase (CAT), and total protein (TP) were found in RTF-fed 20% azolla at 28ppt salinity, while the lowest CAT and TP levels occurred in RTF-fed 60% azolla at 5ppt salinity. The highest aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were recorded in the RTF group fed 60% azolla at 5ppt salinity, with the lowest values seen in the group given 20% azolla at 28ppt salinity. RTF fed a 20% azolla diet at 18ppt salinity exhibited the highest lysozyme value, in contrast to the lowest value observed in the RTF group fed the control diet at 18ppt salinity. In conclusion, this study recommends the utilization of azolla at inclusion levels ranging from 20 to 40%, as it has the potential to notably enhance the immune system and elevate the survival rate of RTF.

Factors associated with treatment responses to pioglitazone in patients with steatotic liver disease: A 3-year prospective cohort study.

The response rate to pioglitazone and the predictive factors for its effects on improving liver biochemistry in patients with steatotic liver disease (SLD) remain elusive, so we aimed to investigate these issues. A 3-year prospective cohort study of 126 Taiwanese patients with SLD treated with pioglitazone (15-30 mg/day) was conducted. Phospholipase domain-containing protein 3 I148M rs738409, methylenetetrahydrofolate reductase rs1801133, aldehyde dehydrogenase 2 (ALDH2) rs671 and lipoprotein lipase rs10099160 single nucleotide polymorphisms were assessed in the patients. Of 126 patients, 78 (61.9%) were men, and the mean and median ages were 54.3 and 56.5 years, respectively. Pioglitazone responders were defined as those with decreased alanine aminotransferase (ALT) levels at 6 months post-treatment, and 105 (83.3%) patients were responders. Compared with non-responders, responders were more frequently women and had higher baseline ALT levels. The proportion of patients with the ALDH2 rs671 GG genotype was lower among responders (38.6% vs. 66.6%, p = .028). Female sex [odds ratio (OR): 4.514, p = .023] and baseline ALT level (OR: 1.015, p = .046; cut-off level: ≥82 U/L) were associated with pioglitazone response. Among responders, the liver biochemistry and homeostasis model assessment of insulin resistance improved from 6 to 24 months post-treatment. The total cholesterol levels decreased within 6 months, while increases in high-density lipoprotein cholesterol levels and decreases in triglyceride levels and fibrosis-4 scores were noted only at 24 months post-treatment. The 2-year cumulative incidences of cardiovascular events, cancers and hepatic events were similar between responders and non-responders. Regarding liver biochemistry, over 80% of Taiwanese patients with SLD had a pioglitazone response, which was positively associated with female sex and baseline ALT levels. Insulin resistance improved as early as 6 months post-treatment, while liver fibrosis improvement was not observed until 24 months post-treatment. The link between the pioglitazone response and the ALDH2 genotype warrants further investigation.