Liver Markers Research Articles

Supplementation with the Traditional Thai Polyherbal Medicine NawaTab Ameliorates Lipid Profiles in High-Fat Diet-Induced Hyperlipidemic Rats.

A tablet formulation developed from Nawametho decoction (NawaTab), a traditional Thai herbal mixture described in the Worayokasan scripture, has been used clinically for several years in the management of borderline hyperlipidemic individuals. Nevertheless, scientific evidence supporting its claims has never been identified. This study aimed to describe the antihyperlipidemic properties of NawaTab in a well-described model of high-fat diet (HFD)-induced hyperlipidemic rats. Decoction of Nawametho containing equal quantities of Aegle marmelos (L.), Carthamus tinctorius L., Hibiscus sabdariffa Linn., Phyllanthus emblica L., Piper longum L., Piper nigrum L., Terminalia bellirica (Gaertn.) Roxb., Terminalia chebula Retz., and Zingiber officinale Roscoe were prepared. The HFD-fed rats were administered NawaTab for 4 consecutive weeks starting from the ninth week of HFD treatment at a dose of 125 mg/kg (p.o.). Anthropometric parameters, serum lipid profiles, lipase activity, and liver and renal functional markers were measured. Histopathological examination of the liver and any steatosis was carried out at the end of this study. Consecutive treatment with NawaTab (125 mg/kg/day) in HFD-induced hyperlipidemic rats caused a significant reduction in serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels. However, at the tested dose, NawaTab failed to prevent the onset of hepatic steatosis and adipose tissue accumulation. No adverse events due to the consumption of NawaTab on liver and kidney function markers were noted. These findings are the first suggestive evidence for the lipid-lowering capability of NawaTab. However, to promote the use of this formulation in the management of borderline hyperlipidemic patients, elucidation of the underlying mechanisms of action, quantification of biological markers, and clinical trials of NawaTab are urgently needed.

In Vivo and In Silico Assessment of the Cardioprotective Effect of Thymus linearis Extract against Ischemic Myocardial Injury.

Myocardial infarction is irreversible cardiac tissue necrosis due to the blockage of one of the arteries. It leads to an insufficient supply of oxygen and nutrients, creating muscular damage in the affected regions. In the present study, aqueous methanolic extract of Thymus linearis was prepared to evaluate its activity against ischemic stress due to free radical production. GC-MS analysis was performed to evaluate the phytochemicals present in the plant extract. A chemical database of 30 compounds was virtually screened against NF-κB, COX2, and MCL, where γ-cadinene, β-bisabolene, and β-caryophyllene were found to be the best interacting ligands. To systematically assess cardioprotective activity against ischemia, isoproterenol and doxorubicin were used to induce cardiotoxicity in rats. The prepared extract of T. linearis (100 mg/kg) was given daily to animals for 21 days before injecting isoproterenol (85 mg/kg of animal weight) subcutaneously in two doses on the 20th and 21st days. In the case of doxorubicin, cardiotoxicity was induced in rats by a single injection (15 mg/kg) on the seventh day, and the extract was given to animals for 10 consecutive days. Animals' blood samples were used to monitor cardiac, liver, and other marker enzymes, including LDH, CPK, and AST. Superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were also assayed in blood plasma to determine the degree of oxidative stress. H&E staining was performed to evaluate cardioprotection by plant extract, showing significant preventive effects in reducing cardiac injury induced by isoproterenol and doxorubicin.

Molecular and biochemical investigation of the protective effects of rutin against liver and kidney toxicity caused by malathion administration in a rat model.

Widely used malathion (MLT) causes environmental pollution, leading to toxicity in many living things, including humans. Rutin (RUT) is a flavonoid with various biological properties. In the present study, the protective effects of rutin against liver and kidney toxicity caused by malathion were investigated. In the study, MLT (100 mg/kg) and RUT (50 or 100 mg/kg) were administered to rats alone or in combination for 28 days. Then, oxidative stress, inflammation, endoplasmic reticulum stress (ERS), apoptosis, and autophagy markers in liver and kidney tissues were analyzed by biochemical and molecular methods. The results showed that MLT caused oxidative stress in both tissues, while RUT showed antioxidant properties and protected these tissues from oxidative damage. Moreover, MLT upregulated the expressions of ATF-6, PERK, IRE1, GRP78, and CHOP, leading to ERS. However, RUT alleviated ER stress and suppressed these markers. The study also found that MLT increased inflammatory, apoptotic, and autophagic markers. All these factors affected liver and kidney functions and caused an increase in plasma ALT, AST, urea, and creatinine levels. On the other hand, it has been observed that RUT may protect liver and kidney tissues from the destructive effect of MLT by showing anti-inflammatory, anti-apoptotic, and anti-autophagic properties. Thus, it was determined that ALT, AST, urea, and creatinine levels decreased after RUT treatment. As a result, it was observed that MLT had a toxic effect on the liver and kidney tissues of rats, and it was determined that this toxicity could be alleviated by RUT treatment.

Abstract 11459: The Biochemical and Physiological Pathways From Obesity to Cardiovascular Disease: A Prospective Cohort Study of 404332 UK Biobank Participants

Background: There are limited effective population measures to control obesity even though it is a major risk factor for chronic diseases. We explored the mechanisms linking obesity and cardiovascular diseases (CVDs), including atherosclerotic CVD (ASCVD) and heart failure (HF), which could be more effective targets for disease prevention. Methods: This is a prospective cohort study of 404,332 UK Biobank participants of white ethnicity who were free from CVDs, chronic diseases, and respiratory disease at baseline and had body mass index (BMI) ≥18.52. Data was collected at the baseline assessment between 2006 and 2010. Linkage to death registrations and hospital admission records was used to ascertain ASCVD and HF outcomes up to late 2021. Obesity is defined as BMI ≥302. Biomarkers included lipids, blood pressure, HbA1c, liver, and kidney function markers chosen based on results from trials and Mendelian randomisation studies. Cox proportional hazard models were used to estimate HRs and 95% confidence intervals (CIs). Mediation analysis based on g-formula was used to identify significant mediators as well as their relative importance for ASCVD and HF separately. Findings: Obesity (BMI ≥30 kg/m2) was associated with an increased risk of ASCVD (HR 1.20, 95% CI 1.16-1.24) and HF (HR 1.75, 95% CI 1.68-1.82) after adjusting for sociodemographic and lifestyle factors and use of statins and medications for blood pressure and diabetes. The strongest mediators for ASCVD were eGFR, blood pressure, and triglycerides, which accounted for 54.63%, 38.15% and 27.69% of the associations respectively; those for HF were eGFR (33.09%), CRP (10.32%), and HbA1c (7.45%). The mediators explained a much higher proportion of excess ASCVD risk than HF risk. Interpretation: Interventions that help individuals living with obesity to maintain healthy levels of lipids, blood pressure, HbA1c, and kidney function could potentially alleviate some of the ASCVD burdens. However, the HF burden could not be meaningfully reduced without weight management.

Comparative efficacy of ternary Cu (II) complex and Zn (II)-complex in amelioration of carbon tetrachloride-induced hepatotoxicity in vivo

Cu (II) and Zn (II) are two of the most favored metals in synthesis chemistry, encompassing their therapeutic potentials. The present study aims to evaluate the comparative ameliorative potential of a group B carcinogen, CCl4-induced hepatotoxicity, by our recently synthesized and characterized ternary Cu and Zn-based complexes in vivo. Three groups of rats were treated with CCl4 alone and with the combination of Cu (II) complex and Zn (II) complex beside the control negative group without any treatment. After completion of the treatment, the samples were subjected to biochemical and histological analysis. The analysis demonstrated extensive alteration in redox status, liver markers, and hepatotoxicity markers in the CCl4, treated group compared to the control group. However, the Cu (II) complex showed significant improvement in most of the parameters under the study. Also, histopathological evaluation and comet assay further consolidated the findings. Hence, this investigation reveals that Cu (II) complex has more substantial ameliorative potential in ceasing CCl4-induced hepatotoxic insults. Therefore, the ternary Cu (II) complex act as a more potent chemotherapeutic agent in cancer treatment with milder side effects than the Zn (II) complex.

Modulatory Effect of Limosilactobacillus fermentum grx08 on the Anti-Oxidative Stress Capacity of Liver, Heart, and Kidney in High-Fat Diet Rats

To explore the modulating effect of Limosilactobacillus fermentum (L. fermentum) grx08 on anti-oxidative stress in the liver, heart, and kidney of high-fat diet in rats, a low-fat diet as a control and a high-fat diet was used to induce oxidative stress injury in rats. L. fermentum grx08 and its heat-inactivated bacteria were used to intervene. The results showed that the high-fat diet had caused oxidative stress injury in the liver, heart, and kidney of rats. L. fermentum grx08 significantly reduced the serum levels of liver, heart, and kidney injury markers (ALT, AST, LDH, CK-MB, UA, and Crea), while restoring the balance of lipid metabolism in the liver. It also enhanced the activity of antioxidant enzymes such as GSH-Px in the liver, heart, and kidney, scavenging NO radicals and reducing the content of MDA, a product of lipid peroxidation, which can regulate the anti-oxidative stress capacity of the liver, heart, and kidney to varying degrees. Among them, L. fermentum grx08 showed better modulating effect on kidney anti-oxidative stress, followed by liver, and the weakest modulating effect on heart. At the same time, L. fermentum grx08 heat-inactivated bacteria also had a partial modulatory effect as well as a similar effect profile to that of live bacteria.

PHYTOMODULATORY EFFECTS OF MURRAYA KOENIGII IN DMBA/TPA INDUCED ANGIOGENESIS, HEPATOTOXICITY AND RENAL TOXICITY DURING SKIN CARCINOGENESIS IN MICE

The present study was aimed to evaluate the protective effects of Hydroethanolic Murraya koenigii leaves extract (HEMKLE) against DMBA/TPA-induced angiogenesis, hepatotoxicity and renal toxicity during skin carcinogenesis in mice. For the study, male LACA mice were divided into four groups: Group I (C), Group II (DMBA/TPA), Group III (HEMKLE), and Group IV (HEMKLE+DMBA/TPA). 7, 12-dimethylbenz(a) anthracene (DMBA), and 12-O-tetradecanoyl phorbol-13-acetate (TPA) were applied on the depilated skin of the mice to raise skin tumors in Group II and Group IV. The chemopreventive response of HEMKLE was evident by histoarchitectural and morphometric analysis of skin/tumors in Group IV (HEMKLE+DMBA/TPA). In addition, HEMKLE administration also decreased the mRNA and protein expression of HIF-1α, HMOX-1, VEGF, bFGF, and ANGPT-2 in Group IV (HEMKLE+DMBA/TPA) when compared to Group II (DMBA/TPA) that suggest its anti-angiogenic effect. Moreover, HEMKLE administration protected the liver and kidney tissues from damages incurred during skin carcinogenesis as evident through histological analysis, assessment of ROS and LPO levels, assessment of liver and kidney function markers (viz., SGOT, SGPT, D-bilirubin, T-bilirubin, ALP, urea, creatinine and BUN) and activities of the antioxidant enzymes in Group IV (HEMKLE +DMBA/TPA) when compared to Group II (DMBA/TPA). The outcome of the present study showed that HEMKLE administration markedly alleviated the angiogenesis and also showed the protective effects against damages incurred in liver and kidney tissues during skin carcinogenesis. However, further extensive studies are needed to explore the efficacy of HEMKLE on metastasis before going to human trials.

Relationship Between Cardiac and Liver Markers with In-hospital Mortality in COVID-19 Patients

Background: COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has turn into a pandemic and has extended all over the world. Since the virus has the potential ability to severely impair heart and liver, analyzing the biochemical parameters is a suitable approach for clinicians to assess the outcome. Methods: This study was conducted along with 614 recognized COVID-19 patients. All samples were from Emergency department of Sina Hospital in Tehran, Iran, from February to May, 2020. Results: A total of 614 COVID-19 patients with mean age of 57.8 years (16-94 years) consisting of 385 (62.7%) male and 229 (37.2%) female were studied. Patients with COVID-19 had no significant difference between cardiac and liver parameters on the presentation and discharge time (p-value≥0.05). Patients with COVID-19 had significant correlation in Lactate dehydrogenase (LDH), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), and Total Bilirubin with recovery and mortality outcome (p-value≤0.05). Also, high sensitivity cardiac Troponin-I, LDH, AST, and ALT in patients with COVID-19 were significantly associated with high in-hospital mortality (p-value<0.05). Conclusion: Several laboratory parameters may ease the evaluation of COVID-19 in-hospital mortality. Cardiac and liver parameters are critical in assisting COVID-19 cases.

Ameliorative Impacts of Wheat Germ Oil against Ethanol-Induced Hepatic and Renal Dysfunction in Rats: Involvement of Anti-Inflammatory, Anti-Apoptotic, and Antioxidant Signaling Pathways.

Wheat germ oil (WGO) is a well-known product with anti-inflammatory and antioxidant properties. The current study aimed to investigate the impacts of WGO against ethanol-induced liver and kidney dysfunction at the serum, anti-inflammatory, antioxidants and anti-apoptotic signaling pathways. Rats received saline orally as a negative control or WGO in a dose of 1.5 mL/kg (1400 mg/kg body weight orally) for 15 days. The affected group received ethanol 50% v/v 10 mL/kg (5 g/kg) body weight orally once a day for consecutive 15 days to induce hepatorenal injuries in ethanolic non-treated group. The protective group received WGO daily 1 h before ethanol administration. Serum (1.5 mL) from blood was extracted and examined for the changes in biochemical assessments in serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), bilirubin, serum γ-glutamyl transpeptidase (GGT), total protein, serum albumin, butyrylcholinesterase (BChE), total cholesterol (TC), total triglyceride (TG), urea, creatinine, uric acid, potassium (K+), Beta-2 microglobulin (β2M), malondialdehyde (MDA), catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD) and aspartate aminotransferase (AST). Kidney and liver homogenate was used to measure MDA, GSH and catalase activities. Quantitative real time PCR (qRT-PCR) was used to express Nrf2 and HO-1 in liver, and NF-kB and kidney injury molecule (KIM-1) in kidneys, which are correlated with oxidative stress and inflammation. Capase-3 and Bcl2 genes were examined using immunohistochemical analysis in the kidney and liver. Ethanol administration induced significant alteration in examined liver and kidney markers (AST, ALT, GGT, ALP, total proteins, urea, creatinine and uric acid). Moreover, alcohol administration decreased antioxidant activities at serum and hepatorenal tissues (GSH, catalase and SOD), while MDA was increased as a tissue degradation marker. Inflammatory cytokines, together with genes of oxidative stress markers (Nrf2 and HO-1), were all affected. At cellular levels, apoptotic marker caspase-3 was upregulated, while antiapoptotic marker B-cell lymphoma 2 (Bcl2), was down regulated using immunohistochemical analysis. Of interest, pretreatment with WGO improved the side effects induced by ethanol on hepatic, renal biomarkers and reversed its impact on serum and tissue antioxidant parameters. Nrf2/HO-1 were upregulated, while NFk-B and KIM-1 were downregulated using real time PCR. Immune reactivities of caspase-3 and Bcl2 genes were restored in the protective group. In conclusion, WGO ameliorated ethanol-induced hepatic and renal dysfunction at the biochemical, molecular and cellular levels by regulating some mechanisms that controls oxidative stress, apoptosis, inflammation and anti-apoptotic pathways.

Gundelia tournefortii inhibits hepatocellular carcinoma progression by lowering gene expression of the cell cycle and hepatocyte proliferation in immunodeficient mice

Gundelia (G.) tournefortii has antibacterial, anti-inflammatory, and hypolipemic effects. We evaluated the anticancer effect of G. tournefortii in an hepatocellular carcinoma (HCC) mouse model of an HCC cell line (Hep3B) injected into NOD.CB17-Prkdc-SCID/NCrHsD male mice. Tumorigenicity was assessed by tumor size, histology, serum α-fetoprotein (αFP), and glypican 3 (GPC3). HCC-related gene expression of the cell cycle (Cyclin-dependent kinase inhibitor 2A (CDNK2A)), proliferation (MKI67), and platelet-derived growth factor receptor α (PDGFA) were measured. HCC cell cycle alterations, apoptosis, and antioxidant markers in serum and liver following treatment with G. tournefortii were determined. Signaling pathways of liver p53 and phosphorylated PI3K, AKT, and mTOR were also evaluated. Results indicate a significant increase in tumor size in HCC animals associated with elevated αFP, GPC3, and MKI67. Tumor markers of p53 and phosphorylated AKT/PI3K/mTOR signaling pathway were diminished, with less proliferating cells and reduced PDGFRA gene expression following G. tournefortii infection. H&E staining showed a remarkable reduction in inflammatory lesions in HCC mice treated with G. tournefortii. This result was in line with a significant delay in the G2/M phase of HCC-primary hepatocytes by 1.39- to 2.4-fold and reduced HCC necrosis associated with inhibited CDNK2A gene expression. Antioxidant activity was significantly lower in the HCC mice than in the control group. Moreover, G. tournefortii inhibited the HCC formation of 3D MCTS spheroids. G. tournefortii treatment markedly restored antioxidant levels and displayed anticancer and antiproliferative effects and could be a promising cancer therapy.

Microbiota and Serum Metabolic Profile Changes in Korean Native Hanwoo Steer in Response to Diet Feeding Systems.

The diversity of bacteria and their function in cattle gastrointestinal tracts can influence animal welfare. Next-generation sequencing (NGS) was used to investigate microbial diversity in the feces of Hanwoo steers reared under natural grazing (GS) and housing (HS) systems. Additionally, serum metabolic parameters, such as liver and kidney markers and mineral and lipid content changes, as well as their correlation with pyrotags, were studied. A total of 6468 ± 87.86 operational taxonomic units (OTUs) were identified in both steer groups, of which 3538 ± 38.17 OTUs were from grazing steer and 2930 ± 94.06 OTUs were from GS. Chao1 index analysis revealed a higher bacterial richness in GS. The dominant bacterial taxa were Bacteroidetes and Firmicutes. GS showed lower Bacteroidetes and higher Firmicutes abundance than HS. The serum of HS showed consistent increases in gamma-glutamyl transpeptidase (γGTP), glucose (GLU), total cholesterol (T-CHO), and triglyceride (TG) levels. The impact of GS on animal health and serum metabolic markers was strongly correlated with microbiota. As shown in this study, grazing has a significant impact on the fecal microbiota at the phylum and family levels, as well as the serum biochemical metabolites of Hanwoo steers.

Bioinformatics Analysis Identifies TNFRSF1A as a Biomarker of Liver Injury in Sepsis TNFRSF1A is a Biomarker for Septic Liver Injury.

Sepsis is a severe disease with high mortality, and liver injury is an independent risk factor for sepsis morbidity and mortality. We analyzed co-differentially expressed genes (co-DEGs) to explore potential biomarkers and therapeutic targets for sepsis-related liver injury. Three gene expression datasets (GSE60088, GSE23767, and GSE71530) were downloaded from the Gene Expression Omnibus (GEO). DEGs were screened between sepsis and control samples using GEO2R. The association of these DEGs with infection and liver disease was analyzed by using the CTD database. GO functional analysis, KEGG pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed to elucidate the potential molecular mechanism of DEGs. DEGs of different tissues in GSE60088 were analyzed again to obtain specific markers of septic liver injury. Mouse model of sepsis was also established by cecal ligation and puncture (CLP), and the expression of specific markers in liver, lung, and kidney tissues was analyzed using Western blot. Here, we identified 21 DEGs in three datasets with 8 hub genes, all of which showed higher inference scores in liver diseases than bacterial infections. Among them, only TNFRSF1A had a liver-specific differential expression. TNFRSF1A was also confirmed to be specifically reduced in septic liver tissues in mice. Therefore, TNFRSF1A may serve as a potential biomarker for septic liver injury.

Red blood cell distribution width derivatives in alcohol-related liver cirrhosis and metabolic-associated fatty liver disease

BACKGROUNDLooking for undiscovered blood markers of liver fibrosis and steatosis still remains an issue worth exploring. There are still plenty of unresolved issues related to the actual role of hematological indices as potential markers of liver function.AIMTo study red blood cell distribution width (RDW), RDW-to-platelet ratio (RPR) and RDW-to-lymphocyte ratio (RLR) in alcohol-related liver cirrhosis (ALC) and metabolic-associated fatty liver disease (MAFLD).METHODSThe study group was composed of 302 people: 142 patients with ALC and 92 with MAFLD; 68 persons were included as controls. RDW, RPR and RLR were measured in each person. Indirect and direct parameters of liver fibrosis were also assessed [aspartate transaminase to alkaline transaminase ratio, aspartate transaminase to platelet ratio index (APRI), fibrosis-4 (FIB-4), gamma-glutamyl transpeptidase to platelet ratio (GPR), procollagen I carboxyterminal propeptide, procollagen III aminoterminal propeptide, transforming growth factor-α, platelet-derived growth factor AB, laminin]. MELD score in ALC patients and non-alcoholic fatty liver disease (NAFLD) fibrosis score together with BARD score were obtained in the MAFLD group. The achieved results were compared to controls. Then a correlation between assessed markers was done. Diagnostic value of each investigated parameter and its suggested cut-off in the research group were evaluated with area under the curve (AUC).RESULTSRDW, RPR and RLR values turned out to be significantly higher in ALC and MAFLD groups compared to controls (ALC: P < 0.0001; NAFLD: P < 0.05, P < 0.0001 and P < 0.0001, respectively). RPR correlated positively with MELD score (P < 0.01) and indirect indices of liver fibrosis (FIB-4 and GPR; P < 0.0001) in ALC patients; negative correlations were found between PDGF-AB and both: RDW and RPR (P < 0.01 and P < 0.0001, respectively). RPR correlated positively with NAFLD fibrosis score and APRI (P < 0.0001) in the MAFLD group; a positive relationship was observed between RDW and FIB-4, too (P < 0.05). AUC values and suggested cut-offs for RDW, RPR and RLR in ALC patients were: 0.912 (> 14.2%), 0.965 (> 0.075) and 0.914 (> 8.684), respectively. AUC values and suggested cut-offs for RDW, RPR and RLR in MAFLD patients were: 0.606 (> 12.8%), 0.724 (> 0.047) and 0.691 (> 6.25), respectively.CONCLUSIONRDW with its derivatives appear to be valuable diagnostic markers in patients with ALC. They can also be associated with a deterioration of liver function in this group.

Effects of a 12-week whole-grain or refined wheat intervention on plasma acylcarnitines, bile acids and signaling lipids, and association with liver fat: A post-hoc metabolomics study of a randomized controlled trial.

We previously showed that whole-grain wheat (WGW) consumption had beneficial effects on liver fat accumulation, as compared to refined wheat (RW). The mechanisms underlying these effects remain unclear. In this study, we investigated the effects of WGW vs. RW consumption on plasma metabolite levels to explore potential underlying mechanisms of the preventive effect of WGW consumption on liver fat accumulation. Targeted metabolomics of plasma obtained from a concluded 12-week double-blind, randomized controlled trial was performed. Fifty overweight or obese men and women aged 45-70 years with mildly elevated levels of plasma cholesterol were randomized to either 98 g/d of WGW or RW products. Before and after the intervention, a total of 89 fasting plasma metabolite concentrations including acylcarnitines, trimethylamine-N-oxide (TMAO), choline, betaine, bile acids, and signaling lipids were quantified by UPLC-MS/MS. Intrahepatic triglycerides (IHTG) were quantified by 1H-MRS, and multiple liver markers, including circulating levels of β-hydroxybutyrate, alanine transaminase (ALT), aspartate transaminase (AST), γ-glutamyltransferase (γ-GT), serum amyloid A (SAA), and C-reactive protein, were assessed. The WGW intervention increased plasma concentrations of four out of 52 signaling lipids-lysophosphatidic acid C18:2, lysophosphatidylethanolamine C18:1 and C18:2, and platelet-activating factor C18:2-and decreased concentrations of the signaling lipid lysophosphatidylglycerol C20:3 as compared to RW intervention, although these results were no longer statistically significant after false discovery rate (FDR) correction. Plasma concentrations of the other metabolites that we quantified were not affected by WGW or RW intervention. Changes in the above-mentioned metabolites were not correlated to change in IHTG upon the intervention. Plasma acylcarnitines, bile acids, and signaling lipids were not robustly affected by the WGW or RW interventions, which makes them less likely candidates to be directly involved in the mechanisms that underlie the protective effect of WGW consumption or detrimental effect of RW consumption on liver fat accumulation. [www.ClinicalTrials.gov], identifier [NCT02385149].

Effect of Green Synthesized Iron Oxide Nanoparticles Using Spinach Extract on Triton X-100-Induced Atherosclerosis in Rats.

The effect of iron oxide nanoparticles (FeONPs) synthesized using Spinacia oleracea leaf extract on Triton X-100-induced atherosclerosis in white Wistar rats was determined. FeONPs were characterized to determine their size, structure, composition, and shape. In vitro antioxidant activity of FeONPs against 2, 2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) was determined. Atherosclerosis was induced by intraperitoneal administration of 5% Triton X-100 (100 mg/kg body weight) for 14 days. Group 1 received standard rat chow and water. Group 2 received 100 mg/kg body weight of Triton X-100 and a standard diet. Group 3 received 100 mg/kg body weight of Triton X-100 followed by 20 mg/kg body weight of atorvastatin for 21 days. Groups 4, 5, and 6 received 100 mg/kg body weight Triton X-100 was followed by variable concentrations of 100, 300, and 500 µg/kg body weight FeONPs, respectively, for 21 days. Blood samples were analyzed for lipid, liver, antioxidant, and cardiovascular markers. Histopathology of the heart was also examined. Characterization revealed the amorphous nature, functional groups, and clustered topography of FeONPs. An upregulated antioxidant activity of FeONPs was observed in a dose-dependent manner. Administration of Triton X-100 showed elevated levels of lipid biomarkers except for high-density lipoprotein (HDL), which decreased in group 2 in comparison to group 1. Liver, antioxidant, and cardiovascular biomarkers all significantly increased. The structural alteration was observed in the heart tissue following histopathology examination. Administration of FeONPs significantly decreased all biomarkers and increased the level of HDL. Also, tissue architecture was restored. Our findings demonstrated that FeONPs were effective in ameliorating Triton X-100-induced atherosclerosis in rats.

IN SILICO PREDICTION OF THE MITIGATIVE POTENTIAL OF CURCUMIN AGAINST DELTAMETHRIN TOXICITY

Deltamethrin (DLM) is a widely used pyrethroid, pest control insecticide due to restriction on the sale of organophosphate. Deltamethrin (DLM) being a potent hepatotoxic compound, that affects physiological functions of liver; however, the implications of the hepatotoxic effects of DLM on the mammalian system and its influence on the hepatic enzymatic activity are still unclear. Curcumin (CUR), a major polyphenol component of Curcuma longa Linn, is a potent antioxidant often used in traditional medicine as an ameliorative agent. However, its underlying mechanism as an anti-oxidant against DLM-toxicity remains unknown. Hence, the present study has been designed to determine the binding affinity of DLM to a hepatic enzyme marker such as Aspartate aminotransferase (AST). Moreover, the study is aimed to delineate the role of CUR on DLM-induced hepatotoxic effects through a computational approach. The molecular docking carried out demonstrated that CUR manifests a stronger binding affinity towards the liver marker enzyme, AST as compared to deltamethrin. This could explain the possible mechanism for inhibition of the toxic influence of DLM- induced reactive oxygen species on liver enzyme activity. Thus, this computational evidence validates the tenet that CUR displays anti-oxidative properties for attenuation of DLM induced hepatotoxicity, alteration in the mechanism of liver marker enzyme and its subsequent impact on hepatic tissue.

GC–MS analysis, and evaluation of protective effect of Piper chaba stem bark against paracetamol-induced liver damage in Sprague-Dawley rats: Possible defensive mechanism by targeting CYP2E1 enzyme through in silico study

The present study attempted to scrutinize the protective effect of the methanolic extract of P. chaba stem bark against paracetamol-induced hepatotoxicity in Sprague−Dawley rats, along with the gas chromatography–mass spectrometry (GC–MS) analysis to identify phytochemicals, which were further docked in the catalytic site of CYP2E1 and the MD simulation for system that plays a major role in the bio-activation of toxic substances that produce reactive metabolites, leading to hepatotoxicity. P. chaba stem methanol extract (250 and 500 mg/kg) were treated orally with the negative control and the negative control silymarin (50 mg/kg) groups. Phytochemical profiling was conducted using GC–MS. In in-silico studies, PyRx software was used for docking analysis and the stability of the binding mode in the target active sites was evaluated through a set of standard MD-simulation protocols using the Charmm 27 force field and Swiss PARAM. Co-administration of P. chaba at both doses with APAP significantly reduced the APAP-augmented liver marker enzymes ALT, AST, ALP, and LDH, along with serum albumin, globulin, hepatic enzymes, histopathological architecture, lipid profiles, total protein, and total bilirubin, and elevated the levels of MDA. The GC–MS analysis indicated that P. chaba extract is enriched in fatty acid methyl esters (46.23 %) and alkaloids (10.91 %) and piperine is represented as a main phytochemical. Among all the identified phytochemicals, piperine (−8.0 kcal/mol) was found to be more interacting and stable with the binding site of CYP2E1. Therefore, all of our findings may conclude that the P. chaba stem extract and its main compound, piperine, are able to neutralize APAP-induced hepatic damage.

Favorable Aspects of Silymarin in Linezolid Treatment Against Diabetic Methicillin-Resistant Staphylococcus aureus (MRSA) Infected Rats

Background: Linezolid used for diabetic methicillin-resistant Staphylococcus aureus (MRSA) infections is limited due to hepatotoxicity, lactic acidosis, anemia, and oxidative stress induced by diabetes and linezolid therapy. Silymarin is a hepatoprotective, antioxidant, antibacterial, and antidiabetic. Objective: The research investigated the role of silymarin in linezolid treatment against MRSA-infected diabetic rats. Methods: Type 2 diabetes mellitus (T2DM) was induced by a high-fat diet (58% calories fat) for 2 weeks, followed by a single intraperitoneal injection of streptozotocin (STZ) 35 mg/kg into Wistar rats. The diabetic rats were rendered neutropenic and subcutaneously injected with 106 CFU/ml of MRSA. Linezolid and silymarin were administered orally at a dose of 50 mg/kg twice daily for 14 days. The bacterial load/abscess, hematological, biochemical, enzymatic parameters, antioxidants, and histopathological studies were performed on the 42nd day. Results: The MRSA was confirmed by PCR assay. The minimum inhibitory concentration of linezolid was found to be 0.5-2 μg/ml. The linezolid treated MRSA infected diabetic rats showed 9.69 x 103 CFU / abscess bacterial count, decreased intestinal alkaline phosphatase (IAP), RBC, antioxidants, elevated lactate, and liver markers than diabetic rats. The silymarin treatment showed a decrease in the bacterial count (2.98 x 103 CFU / abscess), serum lactate, liver markers, increased IAP levels, and antioxidants in linezolid treated diabetic infected rats. Conclusion: The research concluded that silymarin could be a better herbal therapeutic agent that attenuated diabetic and linezolid induced complications in MRSA-infected diabetic rats.

Analysis of alcohol use, consumption of micronutrient and macronutrients, and liver health in the 2017-2018 National Health and Nutrition Examination Survey.

Alcohol use is a major global healthcare burden that contributes to numerous adverse health outcomes, including liver disease. Many factors influence individual susceptibility to alcohol-associated diseases, including nutritional factors. The objective of the current study was to examine inter-relations among alcohol, dietary micronutrients and macronutrient consumption, and liver health by analyzing data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES). Based on self-reported alcohol consumption, NHANES respondents were assigned to one of four categories: never drinkers (lifetime abstainers), non-drinkers (past-year abstainers), moderate drinkers (1/2 drinks per day for females/males, respectively), and heavy drinkers (>1/>2 drinks per day for females/males, respectively, and/or frequent binge drinking). Survey-weighted regression analyses (adjusted for gender, age, race, education, and body mass index) were performed to examine associations between alcohol intake, dietary, and liver health characteristics. Individuals categorized as heavy drinkers were significantly younger, most often well-educated males with low incidences of diabetes and other comorbidities. They consumed the most overall calories and various micronutrients, indicating a diet that was not necessarily nutrient poor. Neither moderate nor heavy drinkers had liver steatosis or fibrosis as measured by liver elastography, although heavy drinkers had modestly elevated plasma biomarkers of liver injury, including ALT, AST, and GGT, compared with the other groups. Our findings suggest that the category of heavy drinkers in the 2017-2018 NHANES consisted of generally healthy individuals with high-energy intake and no evidence of liver steatosis or fibrosis. However, slightly increased plasma liver markers may indicate a risk of future progression to more advanced stages of liver disease over time in some individuals. Several limitations should be considered when interpreting these data, including the potential misclassification of drinking categories and the lack of standardized cutoff scores for fatty liver as assessed by elastography, among others.

Effect of aqueous and ethanol leaves extracts of Justicia carnea on selected biochemical and haematological parameters in Albino Mice

This study investigated the effect of aqueous and ethanol leaves extracts of Justicia carnea on selected biochemical and haematological parameters in albino mice. LD50 for the ethanol extract was carried out using the guidelines proposed by organization for Economic Cooperation and Development (OECD). Twenty four mice were divided into six groups of four mice/group. Groups 1 and 2 received distil water and 3%DMSO respectively as normal control, groups 3 and 4, 5 and 6 received 500 and 1000mg/kgbw of aqueous and ethanol leaves extracts respectively for six days. Mice were sacrificed 24 hours after the sixth day of treatment and blood sample collected for biochemical and haematological investigations. Result of quantitative phytochemical constituent of the leaves revealed the presence of alkaloids (1.01x10-1), terpenoids (8.55 x 10-1), saponin (449.43), sterols (30.58), phenolic acids (38.73), glycosides (39.27), flavonoids (430.24), tannin (744.24) mg/100g, oxalate (102.11) and phytate (12.37) ppm. Aqueous leaves extract showed significant (p≤0.05) increase in PCV, Hb and platelet values, while others were non-significant while ethanol extract was non-significant (p≥0.05) in all haematological parameters when compared to control. Significant decrease (p≤0.05) was observed in AST, ALT activities and Total bilirubin concentration in all the groups for aqueous extract and non-significant differences (p≥0.05) in all liver markers for all ethanol extract treated groups when compared to control. Aqueous and ethanol extracts of Justicia carnea did not have any toxic effect on the experimental animals however aqueous extract boosted haemoglobin level.