Liver Function Markers Research Articles

Effect of melatonin supplementation on exercise-induced alterations in haematological parameters and liver function markers in sedentary young men of Kolkata, India

Effect of melatonin supplementation on exercise-induced alterations in haematological parameters and liver function markers in sedentary young men of Kolkata, India

Association between Liver Function Markers and Menstrual Cycle Irregularity in Korean Female Population.

The liver plays an important role in gonadal steroid hormone metabolism, which can affect reproductive health, including the menstrual cycle. However, evidence from large population-based studies is limited. Therefore, this study aimed to investigate the association between liver function markers and menstrual cycle irregularities in premenopausal Korean women using nationwide data. This study analyzed Data from the Korea National Health and Nutrition Examination Survey 2010-2011. We investigated 3,045 premenopausal women aged 19-59 years. Liver function markers including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase, and fatty liver index were analyzed. Multivariable logistic regression analysis was performed to investigate the association between liver function markers and menstrual cycle irregularity while adjusting for confounding factors. Values were presented as odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analysis was also performed. Baseline characteristic analysis showed that approximately 14.4% of the study population experienced menstrual cycle irregularity. The mean age was 34.5±0.7 years. The highest quartile of serum ALT and AST levels showed significantly higher ORs for menstrual cycle irregularity (adjusted OR, 1.83; 95% CI, 1.26-2.64 and adjusted OR, 1.67; 95% CI, 1.17-2.39, respectively). A similar result was observed in the subgroup analysis. Liver function markers were positively associated with menstrual cycle irregularities. In clinical settings, women of reproductive age with relatively decreased liver function should be considered for regular followup of their reproductive health status.

Liver Function Markers Response to Different Exercise Intensities in Athletes A Single Bout Perspective

Exercise provides considerable health advantages through promoting proper body system functioning, healthy growth and development, and quality of life. The present study investigated the effect of single bout High- Intensity Exercise (HIE) compared to Low-Intensity Exercise (LIE) on liver function markers in athletes. This cross-sectional study was carried out in the Department of Physical Education, Banaras Hindu University, Varanasi (UP). A total of 20 healthy male athletes with age range from 22 to 26 years were randomly selected and underwent 5 minutes of HIE and LIE separated by one week. Blood samples for selected liver function markers were taken pre-exercise, immediately, 10 and 20 minutes post-HIE and LIE, respectively. A repeated measures ANOVA with greenhouse-geisser correction found a significant difference between high and low intensity exercises for SGOT (F=5.881; p<0.05) and SBT (F=7.154; p<0.05) values, while statistically insignificant in the case of SGPT (F=1.572; p>0.05). In high intensity exercise there was statistically significant difference for SGOT (F=7.564; p<0.05) value between different time points. Post hoc analysis with a bonferroni correction showed that SGOT value was significantly increased immediately after the HIE, reducing 10 minutes after the exercise and closely returned to baseline level after 20 minutes of exercise, whereas LIE showed no significant changes. Exercise intensity is important as it triggers liver pathology by asymptomatic modifying liver function markers. These findings can be used to develop and administer exercise training plans for athletes.

M2BPGi Correlated with Immunological Biomarkers and Further Stratified Recurrence Risk in Patients with Hepatocellular Carcinoma

Introduction Novel biomarkers reflecting liver fibrosis and the immune microenvironment may correlate with the risk of hepatocellular carcinoma (HCC) recurrence. This study aimed to evaluate the prognostic value of serum biomarkers in predicting HCC recurrence. Methods Serum biomarkers, including M2BPGi, IL-6, IL-10, CCL5, VEGF-A, soluble PD-1, PD-L1, TIM-3, and LAG-3, were measured in 247 patients with HCC undergoing surgical resection. Factors associated with recurrence-free survival (RFS) and overall survival (OS) were evaluated. The ERASL-post model and IMbrave050 criteria were used to define HCC recurrence risk groups. Results Serum M2BPGi levels significantly correlated with FIB-4 score, APRI, ALBI score, AFP, ALT, AST, IL-10, CCL5, VEGF-A, soluble PD-1, PD-L1, TIM-3, and LAG-3 levels. M2BPGi, VEGF-A, soluble PD-1, and TIM-3 levels significantly correlated with RFS. In multivariate analysis, M2BPGi >1.5 COI (hazard ratio (HR) = 2.100, p < 0.001), tumor size >5 cm (HR = 1.859, p = 0.002), multiple tumors (HR = 2.562, p < 0.001), AFP >20 ng/mL (HR = 2.141, p < 0.001), and microvascular invasion (HR = 1.954, p = 0.004) were independent predictors of RFS. M2BPGi levels significantly stratified the recurrence risk in ERASL-post and IMbrave050 risk groups. An M2BPGi-based model could significantly discriminate RFS in the overall cohort as well as in the IMbrave050 low- and high-risk groups. M2BPGi >1.5 COI was also an independent predictor of OS after resection (HR = 2.707, p < 0.001). Conclusion Serum M2BPGi levels significantly correlated with surrogate markers of liver fibrosis, liver function, and immunology. M2BPGi is a significant predictor of HCC recurrence and survival after resection and could be incorporated into recurrence-prediction models.

Chronic aluminium chloride exposure induces redox imbalance, metabolic distress, DNA damage, and histopathologic alterations in Wistar rat liver.

Aluminium, a ubiquitous environmental toxicant, is distinguished for eliciting a broad range of physiological, biochemical, and behavioural alterations in laboratory animals and humans. The present work was conducted to study the functional and structural changes induced by aluminium in rat liver. Twenty five adult male Wistar rats (150-200 g) were randomly divided into five groups; control group and four Al-treated groups viz: Al 1 (25mg AlCl3/kg b.wt), Al 2 (35mg AlCl3/kg b.wt), Al 3 (45mg AlCl3/kg b.wt), and Al 4 (55mg AlCl3/kg b.wt). Rats in the aluminium-treated groups were administered AlCl3 for 30 days through oral gavage. Aluminium significantly increased the serum levels of liver function markers (ALT, AST, and ALP), phospholipids, and cholesterol. The activities of hepatocyte membrane (ALP, GGT, and LAP) and carbohydrate metabolic (G6P, F16BP, HK, LDH, MDH, ME, and G6PDH) enzymes were significantly altered by AlCl3 administration. Prolonged Al exposure induced oxidative stress in the liver, as evident by significant hepatocellular DNA damage, increased lipid peroxidation, and decreased non-enzymatic and enzymatic antioxidants. The toxic effects observed in this study were AlCl3 dose-dependent. Histopathological examination of liver sections revealed enlargement of sinusoidal spaces, derangement of the hepatic chord, loss of discrete hepatic cell boundaries, congestion of hepatic sinusoids, and degeneration of hepatocytes in Al-intoxicated rats. In conclusion, aluminium causes severe hepatotoxicity by inhibiting the hepatocyte membrane enzymes and disrupting the liver's energy metabolism and antioxidant defence.

Understanding confounding factors allows for accurate interpretation of liver stiffness measurements by ElastQ, a novel 2D shear wave elastography technique.

Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) or two-dimensional shear wave elastography (2D-SWE) is recommended to assess the risk of liver fibrosis and advanced chronic liver disease. Even though both techniques measure liver stiffness, their numerical results often diverge. Confounders and reliability criteria for 2D-SWE have not been systematically investigated. We prospectively recruited participants with paired LSM by VCTE and the novel 2D-SWE technique ElastQ (Philips) in three European tertiary centers. The following parameters were recorded: sex, age, body mass index (BMI), etiology, laboratory markers of liver damage and function, as well as cholestasis, LSM by VCTE and controlled attenuation parameter (CAP), interquartile range (IQR)/median for VCTE-LSM and ElastQ-LSM, and the skin-to-liver capsule distance. We included 840 participants: 447 (53.2%) males; median age 57.0 [IQR:19.0] years; median BMI 25.4 [6.0] kg/m2; median VCTE-LSM 7.25 [9.2] kPa; median ElastQ-LSM 6.7 [5.4] kPa. On uni- and multivariable modeling (adjusted for LSM), we found that the discrepancy increased with liver stiffness and markers of disease severity. Skin-to-liver capsule distance and BMI affected VCTE-LSM more compared to ElastQ-LSM and significantly increased the discordance between the two measurements. The discrepancy of ElastQ-LSM to VCTE-LSM increases with liver stiffness and disease severity. BMI and skin-to-liver capsule distance increase the discrepancy between VCTE- and ElastQ-LSM but affect ElastQ-LSM less. The quality criterion IQR/median ≤ 30% indicates reliable ElastQ-LSM.

Prognostic Utility of dNLR, ALRI, APRI, and SII in COVID-19 Patients with Diabetes: A Cross-Sectional Study.

The coronavirus disease 2019 (COVID-19) pandemic has necessitated the identification of biomarkers that can predict disease severity, particularly in vulnerable populations such as individuals with diabetes. This study aims to evaluate the predictive value of inflammatory and liver function markers, specifically derived Neutrophil to Lymphocyte Ratio (dNLR), aspartate aminotransferase (AST)-to-lymphocyte ratio (ALRI), AST to Platelet Ratio Index (APRI), and Systemic Inflammation Index (SII), in COVID-19 patients with and without diabetes. This cross-sectional study included 336 participants, comprising 168 patients with diabetes matched with 168 without, based on gender, body mass index (BMI), and COVID-19 severity at hospitalization. The study was conducted at Victor Babes Hospital for Infectious Diseases and Pulmonology from January 2021 to December 2023. All participants had a confirmed SARS-CoV-2 infection and met the inclusion criteria of being 18 years or older with type 1 or type 2 diabetes as per American Diabetes Association guidelines. At 3 days post symptom onset, significant differences in inflammatory and liver function markers were observed between the two groups. The dNLR, ALRI, APRI, and SII were notably higher in diabetic patients. At a dNLR cutoff of 2.685, the sensitivity and specificity were 70.312% and 65.978%, respectively, with an AUC of 0.624 (p < 0.001). The ALRI showed a cutoff of 0.812, with a sensitivity of 76.429% and specificity of 69.541% (AUC 0.752, p < 0.001). These markers demonstrated statistically significant hazard ratios at both 3 and 7 days, indicating their predictive relevance for severe COVID-19 outcomes. For instance, at 7 days, SII demonstrated a hazard ratio of 2.62 (CI: 1.29-5.04, p < 0.001), highlighting its strong prognostic capability. The study successfully identified significant differences in inflammatory and liver function markers between COVID-19 patients with and without diabetes, with these markers showing good predictive value for disease severity. The results underscore the potential of these biomarkers, particularly ALRI and SII, as valuable tools in managing COVID-19, aiding in the timely identification of patients at increased risk of severe outcomes.

Influence of Aframomum sceptrum Treatment on Hepatic Toxicity Induced by Monosodium Glutamate in Albino Rats

Monosodium glutamate (MSG) is commonly used as a culinary flavouring, although research suggest that it is toxic to people and laboratory animals, especially in high dosages. The study goal is to determine the impact of Aframomum sceptrum (ataiko) treatment on hepatic induced toxicity by MSG. Thirty-six albino rats (male) with weight of 120 to 210 g were used for the study. The rats were separated into 6 groups in which each group contains six rats. Group 1: normal control. Group 2: MSG only. Group 3 and 4 were given MSG and then treated with 250 and 350 mg/kg b.wt of A. sceptrum extract respectively. Group 5 and 6 were administered only 250 and 350 mg/kg b.wt of A. sceptrum extract, respectively. The MSG groups were given intra-peritoneal injection of MSG solution at single dose of 4253 mg/kg b.wt. A. sceptrum extract was administered three times a week for four weeks beginning two days after the MSG induction. Liver function markers such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and oxidative stress markers such as reduced glutathione (GSH) and malondialdehyde (MDA) were determined in serum and liver. Also, glucose was determined in the serum. The results showed that there were significant (p &lt; 0.05) increased in glucose, AST, ALT and MDA in serum and liver, and decreased in GSH level in the liver of rats given MSG only when compared with normal control. However, A. sceptrum administration significantly (p &lt; 0.05) decreased glucose, AST, ALT and MDA in the serum and liver, and increased GSH level in the liver when compared with MSG only. In conclusion, aqueous extract of A. sceptrum may have beneficial effect in MSG induced toxicity in rats by improving GSH level as well as liver function markers in a dose dependent manner.

Flavone improves liver damage in nicotine-exposed rats via the Nrf2/HO-1 pathway

Objective: To assess the hepatoprotective effects of flavone on nicotine-induced liver damage. Methods: Thirty-six rats were allocated into six groups: the control group, the nicotine group, the flavone alone groups (10 and 25 mg/ kg/body weight), and the nicotine groups treated with flavone (10 and 25 mg/kg/body weight). Liver function, oxidative stress, Nrf2 pathway (HO-1, Nrf2, and Keap-1), and inflammatory markers (IL-17, TNF-α, and NF-κB) were evaluated. Additionally, a histopathological examination of liver tissues was performed. Results: Nicotine increased liver damage, inflammation, and oxidative stress. However, flavone suppressed nicotine-induced liver enzymes, oxidative stress, and inflammation, as manifested by increased antioxidants and decreased malondialdehyde level, liver enzymatic activities, and inflammatory markers. Flavone (10 and 25 mg/kg/body weight) also reduced the level of Keap-1 and increased HO-1 and Nrf2 levels in the liver of nicotine-exposed rats. Conclusions: Flavone has hepatoprotective properties and may slow the progression of liver injury by reducing oxidative stress, liver enzymes, and inflammation possibly via the Nrf2 pathway.

Association of Adiponectin and Oxidized HDL with ABO Blood Groups in Fatty Liver Patients

Non-Alcoholic Fatty Liver Disease (NAFLD) is a group of liver diseases that are not brought on by alcohol usage and are defined by an excessive buildup of fat in the liver cells. Objective: To identify the relationship between the Body Mass Index (BMI) and liver function markers in the study group, as well as Oxidized High-Density Lipoprotein (oxHDL) levels. Methods: This study was conducted at the University of Lahore, for the duration of six months from January 2022 to June 2022. For determining the role of adiponectin and oxHDL, (n=200) patients and divided into two group, healthy group (n=100) and disease group (n=100) participants. Biochemical identification, liver function test, lipid profile test and ELISA was done for analyzing the association with NAFLD. SPSS software was used for statistical analysis. Results: In this study different parameters were used that’s values of parameters mean of cases according to blood group system were varied than normal range, such as adiponectin level, BMI, oxLDL, oxHDL, ALT, AST, ALP, Cholesterol level, d-LDL, Calculated LDL, sdLDL, V-LDL, Triglyceride level, Apolipoprotein-B level was significantly higher and AST/ALT Ratio values, albumin, HDL were slightly less than normal values. O Blood groups was reported very low risk of fatty liver patients due to high adiponectin. Conclusions: From analysis it was concluded, that adiponectin and oxHDL associated with high risk of non-alcoholic fatty liver disorder.

Protective effects of Butylated Hydroxytoluene (BHT) against sodium Arsenite (NaAsO2) - Induced hepatotoxicity in Wistar Rats

One of the major environmental contaminants that can be found on a global scale is arsenic. Sodium arsenite (NaAsO2) is one of the compounds of arsenic which is considered very toxic. Long term exposure to NaAsO2 can cause chemical complications in various organs of the body such as the liver, kidney, testes and brain tissues. Butylated hydroxytoluene (BHT) is an antioxidant that can serve as an antitoxic effect. NaAsO2. In this topic, we examined the chemo-protective effect of BHT on NaAsO2 induced hepatotoxicity in male Wistar rats. Wistar rats (n=42, +120g) were randomly grouped into seven treatment groups: of 7 animals each Control 1(corn oil); Control 2(distilled water); NaAsO2 alone (2.5mg/kg). BHT alone (25 mg/kg); BHT only (25mg/kg); BHT+ NaAsO2 (25mg/kg + 2.5/kg), and BHT+ NaAsO2 (2.5g/kg + 50 mg/kg) and treated for 14 days. Markers of liver functions, inflammation, oxidative stress and antioxidant profile of liver were assayed spectrophotometrically. Our results showed that exposure to NaAsO2 resulted in dramatic increase in the levels of AST, ALT and ALP activity Furthermore, NaAsO2 increased the concentration of oxidative stress markers such as xanthine oxidase (XO) and lipid peroxidation (MDA) and inflammatory markers such as myeloperoxidase (MPO) and nitric oxide (NO) with a concomitant decrease in antioxidant markers such as superoxide dismutase (SOD). Glutathione-S-transferase (GST), and catalase. However, the co-exposure of rats to both BHT and NaAsO2 can result in significant decrease the parameters above. In conclusion, exposure of rats to NaAsO2 causes increased inflammatory and oxidative stress signals, but these harmful effects can be ameliorated by administration of antioxidants such as BHT as confirmed by this research.

Effects of ashwagandha (Withania somnifera) root extract on aging-related changes in healthy geriatric dogs: A randomized, double-blinded placebo-controlled study.

This study aimed to explore the clinical potential of Withania somnifera/ashwagandha root extract (ARE) to mitigate age-related changes in healthy geriatric dogs. We hypothesized that ARE can reduce the effects of advancing age, including physiological changes, immune response decline and susceptibility to diseases, by its immunomodulatory effects. A randomized, double-blind, placebo-controlled trial was conducted in Telangana, India, from July 2022 to September 2022. Twenty apparently healthy dogs, aged 8 years or older, were enrolled. The dogs were divided into two groups to receive ARE (15mg/kg, once daily, orally) or a placebo control. Various parameters, including serum cortisol levels, haematological profiles, biochemical markers, antioxidant indicators and anti-inflammatory responses, were assessed at the initiation of study, day 30, and day 60. The erythrocyte count and haemoglobin levels were significantly increased with ARE (p<0.001), whereas leukocyte count decreased (p<0.05). Moreover, significant decreases in important markers of liver function (alanine aminotransferase, aspartate aminotransferase, albumin and globulin; p<0.001 at day 60), as well as kidney function markers (creatinine and blood urea nitrogen; p<0.001 at days 30 and 60), were observed in ARE-treated dogs compared to the placebo control group. In addition, the levels of markers of oxidative stress (superoxide dismutase, catalase, glutathione and malondialdehyde) were significantly modulated by ARE intervention, indicating strong antioxidant effects. Interestingly, serum cortisol levels reduced significantly with ARE (p<0.001). Compared to baseline, ARE significantly decreased key inflammatory markers, including interferon-γ, tumour necrosis factor-α, nuclear factor kappa light chain enhancer of activated B cells and interleukin-10 (p<0.001) levels at day 60. In conclusion, the findings of this study suggest that ARE has adaptogenic properties in healthy geriatric dogs by improving haematological and biochemical profiles, enhancing antioxidant defence, reducing stress and modulating inflammatory responses.

Association of liver function markers and apolipoprotein E ε4 with pathogenesis and cognitive decline in Alzheimer's disease.

Alzheimer's disease (AD) is a complex neurodegenerative disorder influenced by various factors, including liver function, which may impact the clearance of amyloid-β (Aβ) in the brain. This study aimed to explore how the apolipoprotein E (APOE) ε4 allele affects the relationship of liver function markers with AD pathology and cognition. We analyzed data from two independent cohorts, including 732 participants from the Hallym University Medical Center and 483 from the Alzheimer's Disease Neuroimaging Initiative, each group consisting of individuals with and without the APOE ε4 allele. Cross-sectional analyses evaluated the associations of liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, total bilirubin, and albumin) with AD diagnosis, amyloid positron emission tomography (PET) burden, and cerebrospinal fluid biomarkers for AD (Aβ42, total tau, and phosphorylated tau181) at baseline. Longitudinally, we investigated the associations between these liver enzymes and changes in cognitive performance over the course of a year. Logistic and linear regression models were used to analyze these associations and mediation analyses were conducted to assess whether age and amyloid PET burden mediated these associations. Only in the APOE ε4 carrier group, a high AST to ALT ratio and low ALT levels were significantly associated with AD diagnosis, increased amyloid PET burden, and faster longitudinal decline in cognitive function in both cohorts. In particular, the AST to ALT ratio was associated with cerebrospinal fluid Aβ42 levels exclusively in the APOE ε4 carrier group in the Alzheimer's Disease Neuroimaging Initiative cohort but not with phosphorylated tau181 or total tau levels. Moreover, mediation analyses from both cohorts revealed that in the APOE ε4 carriers group, age did not mediate the associations between liver enzymes and AD diagnosis or amyloid PET burden. However, amyloid PET burden partially mediated the association between liver enzymes and AD diagnosis exclusively in the APOE ε4 carriers group. This study provides valuable insights into the significant association of the APOE ε4 allele with liver enzymes and their potential role in Aβ-related pathogenesis and cognition in AD. Further research is required to elucidate the underlying mechanisms and potential therapeutic implications of these findings.

Sub-chronic Hepatotoxicity Assessment of Ghana Cleanser® in Exposed Wistar Rats

This study evaluated the toxicity of a polyherbal Formulation (Ghana Cleanser®) on liver function markers of exposed albino rats. Thirty (30) male and female rats of the Wistar strain were randomly allotted into six (6) groups with n=5. 10.0 mL/kg distilled water was given to control groups 1 and 4. Polyherbal formulation doses of 374.0 mg/kg and 187.0 mg/kg were administered to groups 2-3 and 5-6, respectively. A modified Lorke's approach was used to compute acute toxicity. Animals were euthanized after 60 days under diethyl ether. Blood was collected for biochemical analyses through cardiac puncture. The liver was excised from each animal and was fixed in 10% buffered formaldehyde and prepared for histological assessment. LD50 of the polyherbal preparation was calculated as 3740 mg/kg (oral). The results indicated an appreciable increase (p&lt;0.05) in ALT activity at 374.0 mg/kg in female rats; while there was no increase recorded at 187.0mg/kg in male rats. A significant increase in ALT activity was recorded at 374 mg/kg in male rats as well and increased AST activities were recorded at 187mg/kg in female rats. In the treated animals of both sexes, ALP activities were significantly elevated. Histopathology assessment of the hepatocytes showed no significant damage at 187 mg/kg in rats of both sexes when compared with their respective controls while some degrees of pathologies such as hepatocyte inflammation, hyperplasia, and congestion were recorded at 374 mg/kg in rats of both sexes. Results suggest caution on the long-term use of the polyherbal mixture due to its hepatotoxic potential.

Using machine learning-based algorithms to construct cardiovascular risk prediction models for Taiwanese adults based on traditional and novel risk factors

ObjectiveTo develop and validate machine learning models for predicting coronary artery disease (CAD) within a Taiwanese cohort, with an emphasis on identifying significant predictors and comparing the performance of various models.MethodsThis study involved a comprehensive analysis of clinical, demographic, and laboratory data from 8,495 subjects in Taiwan Biobank (TWB) after propensity score matching to address potential confounding factors. Key variables included age, gender, lipid profiles (T-CHO, HDL_C, LDL_C, TG), smoking and alcohol consumption habits, and renal and liver function markers. The performance of multiple machine learning models was evaluated.ResultsThe cohort comprised 1,699 individuals with CAD identified through self-reported questionnaires. Significant differences were observed between CAD and non-CAD individuals regarding demographics and clinical features. Notably, the Gradient Boosting model emerged as the most accurate, achieving an AUC of 0.846 (95% confidence interval [CI] 0.819–0.873), sensitivity of 0.776 (95% CI, 0.732–0.820), and specificity of 0.759 (95% CI, 0.736–0.782), respectively. The accuracy was 0.762 (95% CI, 0.742–0.782). Age was identified as the most influential predictor of CAD risk within the studied dataset.ConclusionThe Gradient Boosting machine learning model demonstrated superior performance in predicting CAD within the Taiwanese cohort, with age being a critical predictor. These findings underscore the potential of machine learning models in enhancing the prediction accuracy of CAD, thereby supporting early detection and targeted intervention strategies.Trial registrationNot applicable.

Enhanced thorium decorporation and mitigation of toxicity through combined use of Liv52® and diethylenetriamine pentaacetate

Thorium-232 (Th-232) is a promising fuel for advanced nuclear reactors. However, in case of internal human exposure to Th, there is currently no effective modality for its removal from liver and skeleton or for mitigating its effect. The FDA-approved agent, diethylenetriaminepentaacetate (DTPA), can remove Th and other actinides from blood circulation only. For the first time, a rationally-selected polyherbal hepatoprotective i.e. Liv52® (L52S), was evaluated in-combination with DTPA for its Th decorporation ability in Swiss mice. Inductively-coupled plasma mass spectroscopic analysis showed that oral administration of L52S in conjunction with DTPA significantly decreased Th burden from liver (20 %) and skeleton (33 %) as well as enhanced Th excretion (∼2.5 folds) through urine in comparison to DTPA or L52S alone. The combinatorial therapy was found to be complementary in-action, ameliorating Th-induced tissue damage in liver, spleen, and bone more effectively than monotherapy. Furthermore, markers of liver function (alanine transaminase) and liver inflammation and fibrosis (NF-κB & keratin) further validated the beneficial effect of L52S. The human consumption of L52S for various liver disorders further supports its clinical application for Th decorporation and mitigation of its health effects.

Boiling histotripsy exhibits anti-fibrotic effects in animal models of liver fibrosis

Liver fibrosis is a hallmark of chronic liver disease which could lead to liver cirrhosis or liver cancer. However, there is currently lack of a direct treatment for liver fibrosis. Boiling histotripsy (BH) is an emerging non-invasive high-intensity focused ultrasound technique that can be employed to mechanically destruct solid tumour at the focus via acoustic cavitation without significant adverse effect on surrounding tissue. Here, we investigated whether BH can mechanically fractionate liver fibrotic tissue thereby exhibiting an anti-fibrotic effect in an animal model of liver fibrosis. BH-treated penumbra and its identical lobe showed reduced liver fibrosis, accompanied by increased hepatocyte specific marker expression, compared to the BH-untreated lobe. Furthermore, BH treatment improved serological liver function markers without notable adverse effects. The ability of BH to reduce fibrosis and promote liver regeneration in liver fibrotic tissue suggests that BH could potentially be an effective and reliable therapeutic approach against liver fibrosis.

Suppression of the Epithelial-Mesenchymal Transition and Maintenance of the Liver Functions in Primary Hepatocytes through Dispersion Culture within a Dome-Shaped Collagen Matrix.

Primary hepatocytes are valuable for studying liver diseases, drug-induced liver injury, and drug metabolism. However, when cultured in a two-dimensional (2D) environment, primary hepatocytes undergo rapid dedifferentiation via an epithelial-mesenchymal transition (EMT) and lose their liver-specific functions. On the other hand, a three-dimensional (3D) culture of primary hepatocyte organoids presents challenges for analyzing cellular functions and molecular behaviors due to strong cell-cell adhesion among heterogeneous cells. In this study, we developed a novel dispersion culture method of hepatocytes within a dome-shaped collagen matrix, overcoming conventional limitations. The expression levels of EMT-related genes were lower in rat primary hepatocytes cultured using this method for 4 d than in cells cultured using the 2D method. Furthermore, albumin production, a marker of liver function, declined sharply in rat primary hepatocytes cultured in two dimensions from 6.40 µg/mL/48 h on day 4 to 1.35 µg/mL/48 h on day 8, and declined gradually from 4.92 µg/mL/48 h on day 8 to 3.89 µg/mL/48 h on day 14 in rat primary hepatocytes cultured using our new method. These findings indicate that the newly developed culture method can suppress EMT and maintain liver functions for 14 d in rat primary hepatocytes, potentially expanding the utility of primary hepatocyte cultured by using conventional 3D methods.

Phytochemicals-based investigation of Rubia cordifolia pharmacological potential against letrozole-induced polycystic ovarian syndrome in female adult rats: In vitro, in vivo and mechanistic approach

Polycystic Ovarian Syndrome (PCOS) is a metabolic, reproductive, and endocrine disorder affecting women of fertile age. This study aimed to formulate a phytochemicals-based standardized aqueous ethanolic extract of Rubia cordifolia (SERC) to explore its pharmacological potential in PCOS-induced female rats and elucidate its mechanism. HPLC analysis revealed the presence of phytochemicals such as chlorogenic acid, p-coumaric acid, gallic acid, and kaempferol. Thirty female adult rats were divided into two groups for induction of PCOS (5 female rats in the normal control group + 25 female rats in the disease-induced group). PCOS was induced by administering letrozole (1 mg/kg p.o.) for 6 weeks. After PCOS induction, animals of the disease-induced group were divided into five groups: one group used as disease control (PCOS) group, one group on metformin (20 mg/kg), and three groups on SERC (200, 400, and 600 mg/kg). Histopathological analysis showed that PCOS induction reduced corpus luteum and developing follicles and increased cystic follicles. In comparison, SERC treatment improved ovulation with more primary and developing follicles. SERC reduced the serum insulin, LH surge, and testosterone levels while improving the FSH, estrogen, and progesterone serum levels. SERC significantly improved the oxidation status of the liver and normalized the lipid profile and liver function markers. In conclusion, SERC treated PCOS, and the suggested mechanism might be the restoration of aromatase activity and background inflammatory status improvement in ovaries.

Efficacy of Ayurveda interventions and lifestyle versus lifestyle interventions alone in grade I and II non-alcoholic fatty liver disease: Protocol for a multicenter exploratory pilot randomized controlled trial

Abstract INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a worldwide public health issue affecting 20%–30% of adults, with dominance in men, particularly in the obese population. Current interventions focus on lifestyle modifications, highlighting the need for effective pharmacological options. This study explores the clinical efficacy of Arogyavardhini Vati and Pippalyadyasava, traditional Ayurvedic formulations, in the management of NAFLD. BACKGROUND AND RATIONALE: With Ayurvedic medicine emphasizing holistic well-being, this study is aimed to assess the efficacy of Ayurveda interventions viz., Arogyavardhini Vati and Pippalyadyasava combined with lifestyle modifications in grade I and II NAFLD. MATERIALS AND METHODS: The study includes individuals aged 18–60 years and diagnosed with NAFLD of grade I or II. The intervention arm receives Arogyavardhini Vati and Pippalyadyasava along with lifestyle modifications, while the control group adopts lifestyle modifications for 90 days. Both groups are then followed up for more than 30 days with lifestyle modifications ongoing. Primary outcomes include the change in the fibroscan score and controlled attenuation parameter value or magnetic resonance imaging proton density fat fraction. Secondary outcomes are changes in liver function markers, lipid profile, HbA1C, Body Mass Index, and Fatty Liver Index. CONCLUSION: This study may inform about the efficacy of the Ayurvedic interventions adjuvant to lifestyle modification in the management of NAFLD. TRIAL REGISTRATION: CTRI/2022/02/040321 dated February 15, 2022.