Markers Of Liver Damage Research Articles

A healthy lifestyle is prospectively associated with lower onset of metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an unhealthy lifestyle. However, there is limited prospective evidence regarding the association between combined lifestyle factors and MASLD. This study aims to test the association of a combination of lifestyle components, expressed as a healthy lifestyle index (HLI), and unhealthful eating behavior habits with MASLD, insulin resistance (IR), liver fibrosis, and metabolic dysfunction-associated steatohepatitis. A prospective cohort study was conducted among participants of metabolic and hepatic screening surveys. MASLD was evaluated by ultrasonography or controlled attenuation parameter at 2 time points to assess new-onset, persistence, or remission, and IR was estimated by homeostasis model assessment. Presumed liver fibrosis and metabolic dysfunction-associated steatohepatitis were evaluated using FibroMax biomarkers. The HLI was calculated as the sum of 4 lifestyle components: nonsmoking, healthy weight, healthy diet, and physical activity. The final cohort included 315 subjects with 6.7 years of follow-up, 40-70 years old. In multivariable analyses, a favorable lifestyle (≥3 components) was independently associated with lower odds of new-onset MASLD (OR = 0.42; 95% CI: 0.19-0.90). Similarly, a favorable lifestyle was associated with lower odds of new-onset/persistent (vs. never/remission) MASLD and IR, respectively (OR = 0.49; 95% CI: 0.30-0.80; OR = 0.40; 95% CI: 0.24-0.66). There was a dose-response association between HLI and new-onset/persistent MASLD and IR. A favorable lifestyle was associated with lower odds of new-onset metabolic dysfunction-associated steatohepatitis (OR = 0.50; 95% CI: 0.27-0.95). Adjusting for HLI, unhealthful eating behavior habits were associated with higher odds of MASLD prevalence (OR = 1.81; 95% CI: 1.07-3.06). Adherence to a healthy lifestyle is prospectively associated with lower odds of MASLD, markers of liver damage, and IR. A holistic approach that considers overall lifestyle and eating behavior may be useful for preventing MASLD.

Protective Effects of Plum on Liver and Gut Injury in Metabolic Dysfunction-Associated Fatty Liver Disease.

Metabolic dysfunction-associated fatty liver disease (MASLD), a persistent liver condition associated with metabolic syndrome, is primarily caused by excessive fructose intake and a typical Western diet. Because there is currently only one approved treatment, lifestyle and dietary interventions are crucial. This study assessed the effects of dietary intervention involving freeze-dried plum (FDP), a natural source of antioxidants containing diverse polyphenols. This study aimed to assess its potential as a protective agent against the gut-liver axis and its therapeutic effects on liver injury and gut permeability issues associated with MASLD. We indicate that 10% FDP intake restored gut barrier proteins and reduced serum endotoxin levels in the MASLD mouse models. Additionally, 10% FDP intake significantly reduced hepatic oxidative stress, lipid metabolism, and fibrosis marker levels. Interestingly, FDP intake significantly reduced the levels of inflammatory cytokine tumor necrosis factor-α and markers of liver damage, such as serum alanine aminotransferase/aspartate aminotransferase and hepatic triglycerides. These results highlight that dietary intervention with FDP that acts as a natural antioxidant may be a significant protective and therapeutic agent against liver and gut damage caused by MASLD.

Impact of Imperata Cylindrica polysaccharide on liver lipid metabolism disorders caused by hyperuricemia.

Elevated uric acid levels are associated with lipid metabolism disorders. The effects of Imperata cylindrica polysaccharide (ICPC-a) were explored using a hyperuricemia mouse model and a uric acid-induced HepG2 hepatocyte model. ICPC-a significantly improved total cholesterol, triglycerides, low-density lipoprotein levels, and hepatic lipid deposition in hyperuricemia mice. The liver/body weight ratio decreased, and markers of liver damage, inflammation, and dyslipidemia improved. Metabolomics analysis suggested that ICPC-a modulates lipid metabolism by influencing the glycerophospholipid pathway and the enzyme LPCAT3. Stable HepG2 cell lines with knocked-down LPCAT3 were constructed, and Western blot and RT-PCR were used to assess the impact of its knockdown on lipid metabolism under uric acid stimulation. In cells with reduced LPCAT3 expression, ICPC-a was still able to alleviate uric acid-induced lipid accumulation, though the effect was less pronounced compared to cells with normal LPCAT3 levels. However, the effectiveness was diminished compared to cells where LPCAT3 was not knocked down. These findings indicated that LPCAT3 was an important target through which ICPC-a regulated lipid metabolism disorders induced by hyperuricemia. These discoveries emphasized that ICPC-a, as a prebiotic, could modulate hepatic lipid accumulation and inflammation, contributing to the maintenance of hepatic lipid homeostasis.

Circulating microRNA-21, microRNA-122, and microRNA-222 as diagnostic biomarkers for hepatitis c virus-related hepatocellular carcinoma

Background and aimMicroRNAs (miRs) are now a well-known subject in various tumor genesis and are studied as early diagnostic biomarker. Many arrays of miRs were incorporated in the pathogenesis of HCV-related hepatocellular carcinomas (HCV-HCC). In this respect, we aimed to evaluate the diagnostic role of circulating miR-21, miR-122, and miR-222 in Egyptian patients with HCV-HCC.Patient and methodsBetween June 2018 and April 2019, a cross-sectional comparative study was designed to evaluate the circulating miR-21, miR-122, and miR-222 by quantitative Real-Time PCR. For analytical purposes, patients were categorized into three groups: chronic HCV group (CHC-group, n = 22), HCV-related liver cirrhosis (LC-group, n = 22), and HCV-related hepatocellular carcinoma (HCV-HCC-group, n = 54).ResultsSerum levels of miR-21 and miR-222 increased with the progressive course from CHC to LC and HCC; p < .001. Serum levels of miR-122 in HCC patients were significantly lower than non-HCC patients (CHC and LC patients, n = 44); p < .001. However, the differences in levels of serum miR-122 between CHC and LC were not statistically significant; P = 0.8.ROC curve analysis showed that the sensitivity and specificity of miR-21 were 61.1% and 95.5%, miR-222 were 71.7% and 93.2%, and miR-122 were 98.2% and 100%. The positive predictive value for miRNA-21, miRNA-122, and miRNA-222 were 13.4%, 93.3%, and 10.5% respectively. The Negative predictive value for miRNA-21, miRNA-122, and miRNA-222 were 94.3%, 97.8%, and 92.7% respectively.ConclusionMiR-21 and miR-222 could be potential markers for advanced liver damage, while miR-122 had the best diagnostic accuracy and could be a promising marker for detection of HCC.

Copaiba Oleoresin Improves Weight Gain and IL-10 Concentration, with No Impact on Hepatic Histology, in Liver Cirrhosis.

Copaifera sp. is a native tree in the Amazon region. Copaiba oleoresin has components such as sesquiterpenes, which have anti-inflammatory and antioxidant potential. Liver cirrhosis is the end stage of liver disease with limited therapeutic options. We aimed to evaluate the effect of copaiba oleoresin supplementation on the liver of animals with thioacetamide (TAA)-induced cirrhosis. For the induction of liver cirrhosis, 100 mg/kg of TAA was administered intraperitoneally twice a week for 8 weeks. A total of 200 mg/kg/day of copaiba oleoresin was administered via gavage for the same period. Copaiba oleoresin supplementation improved cirrhosis-associated cachexia by increasing weight gain and body fat. In addition, copaiba oleoresin attenuated systemic inflammation, as shown by the decrease in the circulating C-reactive protein. In the liver, the copaiba oleoresin decreased carbonyl proteins and increased IL-10 compared with TAA-treated rats. TAA groups demonstrated increased SOD, catalase, GST, and GSH activity in the liver. In conclusion, the supplementation of copaiba oleoresin demonstrated a beneficial systemic effect in alleviating cirrhotic cachexia and antioxidant and anti-inflammatory action in the liver. However, it failed to improve the serological and histological markers of liver damage, which could be associated with the advanced stage of the disease.

Exploring the antioxidant and protective effects of Marsdenia thyrsiflora Hook.f. leaf extract against carbon tetrachloride-induced hepatic damage in rat models.

Medicinal plants are vital to healthcare, yet many remain unexplored. Marsdenia thyrsiflora Hook.f., from Bangladesh's Bhawal Forest, lacks research on its medicinal properties, especially its antioxidant capacities and protection against CCl4-induced liver toxicity. This study aims to evaluate the antioxidant properties of M. thyrsiflora leaf extract to determine its protective effects on rodents against CCl4-induced liver injury. After extraction, the total phenol, flavonoid content, and antioxidant capacity of the leaf extract were measured using established protocols. Free radical scavenging abilities were evaluated with 2,2'-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) assays. Additionally, reducing power was assessed through cupric-reducing and ferric-reducing assays. Based on the OECD 420 recommendation, acute toxicity was tested on Swiss albino mice to establish an effective and safe dosage. For the hepatoprotective study, Sprague-Dawley rats were pre-treated with M. thyrsiflora leaf methanolic extract (MTLM) at 250 and 500mg/kg body weight, and CCl4 was administered to induce liver damage. Serum hepatic enzyme levels (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT)), lipid profile (total cholesterol, triglycerides), total bilirubin, and markers of lipid peroxidation (Malondialdehyde (MDA)) were measured. The activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) were also evaluated to assess oxidative stress. The results demonstrated that MTLM, rich in phenolic and flavonoid content, exhibits significant antioxidant activities in DPPH and NO radical scavenging assays, as well as in reducing power assays. The acute toxicity study confirmed the safety of MTLM, with no adverse effects observed even at high doses. For the hepatoprotective study, rats were administered CCl4 to induce liver damage, followed by treatment with MTLM. Results showed that MTLM significantly reduces liver damage markers such as elevated serum hepatic enzyme levels, lipid profile, total bilirubin, and lipid peroxidation and improves the activities of GSH and key antioxidant enzymes such as SOD and CAT. Histopathological analysis corroborated these findings, displaying reduced necrosis, inflammation, and edema in liver tissues treated with MTLM. MTLM extract exhibits potent antioxidant and hepatoprotective properties. Its ability to attenuate oxidative stress, enhance antioxidant enzyme activities, and facilitate histopathological changes in the liver highlights its potential as a natural therapeutic agent for liver damage. However, further investigation is required to understand its molecular processes, safety profiles, and active component characterization.

Association between Liver Damage and Disease Progression Markers with Mortality Risk and Mechanical Ventilation in Hospitalized COVID-19 Patients: A Nationwide Retrospective SARSTer Study.

(1) Background: Liver damage is an important component of acute COVID-19, and the advancement of preexisting liver disease is associated with a worse prognosis; (2) Methods: A nationwide retrospective study including 7444 patients aimed to evaluate levels of selected markers of liver damage and disease advancement and their association with mortality and mechanical ventilation (MV); (3) Results: Elevation of the following markers in multivariate models were associated with increased odds of mortality: Alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH), fibrosis-4 score (FIB-4), AST-to-platelet ratio index (APRI), and decreased levels of platelet count (PLT). Elevated levels of AST, LDH, APRI, FIB-4, and the AST/ALT ratio and decreased levels of PLT were associated with increased odds of MV in multivariate models. The best predictive accuracy against mortality was achieved with FIB-4 with AUC = 0.733 (95% CI, 0.718-0.749) at the optimal cut-off point of 2.764, while against MV was achieved with LDH with AUC = 0.753 (95% CI, 0.727-0.778) at the optimal cut-off point of 449.5 IU/L. (4) Conclusions: Our study confirms that the advancement of liver damage contributes to a worse prognosis in COVID-19 patients. Markers for liver damage and the advancement of liver disease can provide predictive value in clinical practice among COVID-19 patients.

Targeting Oxidative Stress: The Potential of Vitamin C in Protecting against Liver Damage after Electron Beam Therapy.

Background: Radiation-induced liver disease (RILD) is a severe complication arising from radiotherapy, particularly when treating abdominal malignancies such as hepatocellular carcinoma. The liver's critical role in systemic metabolism and its proximity to other abdominal organs make it highly susceptible to radiation-induced damage. This vulnerability significantly limits the maximum safe therapeutic dose of radiation, thereby constraining the overall efficacy of radiotherapy. Among the various modalities, electron beam therapy has gained attention due to its ability to precisely target tumors while minimizing exposure to surrounding healthy tissues. However, despite its advantages, the long-term impacts of electron beam exposure on liver tissue remain inadequately understood, particularly concerning chronic injury and fibrosis driven by sustained oxidative stress. Objectives: to investigate the molecular and cellular mechanisms underlying the radioprotective effects of vitamin C in a model of radiation-induced liver disease. Methods: Male Wistar rats (n = 120) were randomly assigned to four groups: control, fractionated local electron irradiation (30 Gy), pre-treatment with vitamin C before irradiation, and vitamin C alone. The study evaluated the effects of electron beam radiation and vitamin C on liver tissue through a comprehensive approach, including biochemical analysis of serum enzymes (ALT, AST, ALP, and bilirubin), cytokine levels (IL-1β, IL-6, IL-10, and TNF-α), and oxidative stress markers (MDA and SOD). Histological and morphometric analyses were conducted on liver tissue samples collected at 7, 30, 60, and 90 days, which involved standard staining techniques and advanced imaging, including light and electron microscopy. Gene expression of Bax, Bcl-2, and caspase-3 was analyzed using real-time PCR. Results: The present study demonstrated that fractional local electron irradiation led to significant reductions in body weight and liver mass, as well as marked increases in biochemical markers of liver damage (ALT, AST, ALP, and bilirubin), inflammatory cytokines (IL-1β, IL-6, and TNF-α), and oxidative stress markers (MDA) in the irradiated group. These changes were accompanied by substantial histopathological alterations, including hepatocyte degeneration, fibrosis, and disrupted microvascular circulation. Pre-treatment with vitamin C partially mitigated these effects, reducing the severity of the liver damage, oxidative stress, and inflammation, and preserving a more favorable balance between hepatocyte proliferation and apoptosis. Overall, the results highlight the potential protective role of vitamin C in reducing radiation-induced liver injury, although the long-term benefits require further investigation. Conclusions: The present study highlights vitamin C's potential as a radioprotective agent against electron beam-induced liver damage. It effectively reduced oxidative stress, apoptosis, and inflammation, particularly in preventing the progression of radiation-induced liver fibrosis. These findings suggest that vitamin C could enhance radiotherapy outcomes by minimizing liver damage, warranting further exploration into its broader clinical applications.

Glycidol-induced hepatocyte apoptosis via endoplasmic reticulum stress: The underlying role of the gut-liver axis

Glycidol (CAS: 556-52-5), a known carcinogen and genotoxicant, is often found in refined vegetable oils. Human exposure predominantly occurs through consumption of these oils and their byproducts, which contain glycidyl esters (GEs). Upon ingestion, GEs are metabolized to release glycidol, posing substantial health hazards. Historical studies have reported the tumorigenic properties of glycidol across various organs in mice models, encompassing the stomach, liver, lungs, brain, mammary gland, and skin. In this study, we employed a Balb/c mice model to investigate the hepatotoxic effects of glycidol following exposure to escalating doses (0, 25, 50, and 100 mg/kg bw/day). The hepatotoxicity was evidenced by a significant elevation in liver enzymes (ALT, AST), indicative of liver cell damage. Furthermore, biochemical analysis revealed heightened levels of oxidative stress indicators (SOD, MDA, GSH) and the upregulation of endoplasmic reticulum stress proteins, underscoring the cellular stress response. The induction of hepatocyte apoptosis served as a direct marker of liver damage caused by glycidol exposure. Additionally, glycidol altered the composition of intestinal microbiota and short-chain fatty acids (SCFAs), which unbalanced homeostasis. Gut barrier integrity markers (ZO-1, Claudin-1, Occludin, TLR4, LPS) indicated increased permeability of harmful substances to the liver via the gut-liver axis, which exacerbated hepatic injury. These findings highlight glycidol's disruption of gut homeostasis and its hepatotoxic potential.

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.

Treatment with 1.25% cholesterol enriched diet produces severe fatty liver disease characterized by advanced fibrosis and inflammation and impaired autophagy in mice

Nonalcoholic fatty liver disease (NAFLD) is reaching pandemic proportions due to overnutrition. The understanding of advanced stages that recapitulate the human pathology is of great importance to get a better mechanistic insight. We hypothesized that feeding of WT (C57BL) mice with a diet containing a high content of fat (21%), sugar (41.5%) and 1.25% of cholesterol (called from now on high fat, sucrose and cholesterol diet, HFSCD) will reproduce the characteristics of disease severity. Analysis of 16 weeks HFSCD-fed mice demonstrated increased liver weight and plasmatic liver damage markers compared with control diet (CD)-fed mice. HFSCD-fed mice developed greater hepatic triglyceride, cholesterol and NEFA content, inflammation and NAFLD activity score (NAS) indicating an advanced disease. HFSCD-fed mice displayed augmented hepatic total CD3+ T and Th9 lymphocytes, as well as reduced Th2 lymphocytes and CD206 anti-inflammatory macrophages. Moreover, T cells and anti-inflammatory macrophages correlated positively and inversely, respectively, with intrahepatic cholesterol content. Consistently, circulating cytotoxic CD8+ T lymphocytes, Th1, and B cell levels were elevated in HFSCD-fed WT mice. Hepatic and adipose tissue expression analysis demonstrated changes in fibrotic and metabolic genes related with cholesterol, triglycerides, and fatty acid synthesis in HFSCD-fed WT. These mice also exhibited reduced antioxidant capacity and autophagy and elevated ERK signaling pathway activation and CHOP levels. Our results indicate that the feeding with a cholesterol-enriched diet in WT mice produces an advanced NAFLD stage with fibrosis, characterized by deficient autophagy and ER stress along with inflammasome activation partially via ERK pathway activation.

Efficacy and Safety of BoozLiv™ as an add on therapy in patients with alcoholic liver disease: An open-label, randomized controlled trial

BackgroundAlcoholic Liver Disease (ALD) poses a significant global health threat, contributing to millions of deaths each year. Despite the well-established link between chronic alcohol consumption and liver damage, treatment options remain limited, emphasizing the need for innovative approaches. MethodsAn open-label, randomized controlled trial was conducted in India, involving 68 adult ALD patients over a 12-week period. The patients were randomized into two groups: one receiving standard therapy and the other receiving standard therapy along with BoozLiv™ syrup. Liver function tests, Model for End-Stage Liver Disease (MELD) scores, and safety parameters were assessed at various intervals. ResultsThe study demonstrated that BoozLiv™ syrup, as an add-on therapy, significantly reduced total bilirubin, direct bilirubin, SGOT, SGPT, ALP, and GGT levels compared to standard therapy alone (p ​< ​0.05). The MELD score, indicative of liver function, showed a substantial improvement in the BoozLiv™ group (p ​< ​0.01). Safety analysis revealed that BoozLiv™ was well-tolerated, with only minor adverse effects such as nausea and vomiting reported. ConclusionBoozLiv™ syrup, used in conjunction with standard therapy, showed promising results in improving liver function and reducing liver damage markers in ALD patients. The safety profile was favorable and no patient has withdrawn their consent due to adverse events. Further long-term studies in larger populations are warranted to validate these findings and establish BoozLiv™ as a potential therapeutic option for ALD.

Protective Effects of Hepatocyte Stress Defenders, Nrf1 and Nrf2, against MASLD Progression.

Progression of metabolic dysfunction-associated steatites liver disease (MASLD) to steatohepatitis (MASH) is driven by stress-inducing lipids that promote liver inflammation and fibrosis, and MASH can lead to cirrhosis and hepatocellular carcinoma. Previously, we showed coordinated defenses regulated by transcription factors, nuclear factor erythroid 2-related factor-1 (Nrf1) and -2 (Nrf2), protect against hepatic lipid stress. Here, we investigated protective effects of hepatocyte Nrf1 and Nrf2 against MASH-linked liver fibrosis and tumorigenesis. Male and female mice with flox alleles for genes encoding Nrf1 (Nfe2l1), Nrf2 (Nfe2l2), or both were fed a MASH-inducing diet enriched with high fat, fructose, and cholesterol (HFFC) or a control diet for 24-52 weeks. During this period, hepatocyte Nrf1, Nrf2, or combined deficiency for ~7 days, ~7 weeks, and ~35 weeks was induced by administering mice hepatocyte-targeting adeno-associated virus (AAV) expressing Cre recombinase. The effects on MASH, markers of liver fibrosis and proliferation, and liver tumorigenesis were compared to control mice receiving AAV-expressing green fluorescent protein. Also, to assess the impact of Nrf1 and Nrf2 induction on liver fibrosis, HFFC diet-fed C57bl/6J mice received weekly injections of carbon tetrachloride, and from week 16 to 24, mice were treated with the Nrf2-activating drug bardoxolone, hepatocyte overexpression of human NRF1 (hNRF1), or both, and these groups were compared to control. Compared to the control diet, 24-week feeding with the HFFC diet increased bodyweight as well as liver weight, steatosis, and inflammation. It also increased hepatocyte proliferation and a marker of liver damage, p62. Hepatocyte Nrf1 and combined deficiency increased liver steatosis in control diet-fed but not HFFC diet-fed mice, and increased liver inflammation under both diet conditions. Hepatocyte Nrf1 deficiency also increased hepatocyte proliferation, whereas combined deficiency did not, and this also occurred for p62 level in control diet-fed conditions. In 52-week HFFC diet-fed mice, 35 weeks of hepatocyte Nrf1 deficiency, but not combined deficiency, resulted in more liver tumors in male mice, but not in female mice. In contrast, hepatocyte Nrf2 deficiency had no effect on any of these parameters. However, in the 15-week CCL4-exposed and 24-week HFFC diet-fed mice, Nrf2 induction with bardoxolone reduced liver steatosis, inflammation, fibrosis, and proliferation. Induction of hepatic Nrf1 activity with hNRF1 enhanced the effect of bardoxolone on steatosis and may have stimulated liver progenitor cells. Physiologic Nrf1 delays MASLD progression, Nrf2 induction alleviates MASH, and combined enhancement synergistically protects against steatosis and may facilitate liver repair.

Impact of Intermittent Fasting and Dietary Restriction on Redox State, Energetic Metabolism, and Liver Injury in Common Bile Duct Ligation Model.

The aim of this work was to test whether we can treat cholestasis with dietary approaches applied after the onset of the disease. The effects of intermittent fasting and dietary restriction on liver damage caused by common bile duct ligation (BDL) in rats were studied, with particular attention paid to changes in the activity of enzymes of energy metabolism and antioxidant protection. Morphological changes in liver tissue and serum markers of liver damage were assessed in rats with BDL kept for one month on ad libitum diet, intermittent fasting, or 35% dietary restriction. We studied parameters of glucose metabolism (activity of glycolysis and gluconeogenesis enzymes), TCA cycle, and indicators of oxidative stress and redox status of the liver tissue. Dietary restriction resulted in an increase in gluconeogenesis activity, antioxidant capacity, and autophagy activation. When implemented after BDL, none of the dietary restriction protocols reduced the level of oxidative stress, detrimental morphological and biochemical alterations, or the fibrosis progression. Thus, under severe damage and oxidative stress developing in cholestasis, dietary restrictions are not hepatoprotective and can only be used in a pre-treatment mode.

Antidiabetic potential of Selenium nanoparticles and plasma-rich platelets in diabetic mice

Diabetes mellitus is a widespread endocrine disorder, which is categorized as the fourth leading cause of global mortality. Allopathic medicine has yet to provide a satisfactory cure for this condition. Consequently, there is an urgent demand for innovative antidiabetic treatment approaches with enhanced management and minimum side effects and costs. The study investigated the synergistic antidiabetic potential of combining selenium nanoparticles (Se NPs) and plasma-rich platelets (PRP) in diabetic mice. Antidiabetic activity of the proposed combination (Se NPs and PRP) was evaluated from histopathological and biochemical perspectives. The experiment involved alloxan monohydrate induced diabetic mouse model. In the in vivo study, several biochemical parameters for assessing the antidiabetic effect of the novel combination of (Se NPs and PRP) were performed such as blood glucose levels, body weight, lipid profiles, and liver damage markers (AST and ALT). Scavenging antioxidant activity was assessed by evaluation levels of hepatic and renal GSH, MDA, SOD, and CAT activities. Complete histopathological examinations of vital internal organs were carried out. Results revealed that combining Se NPs and PRP presents a novel approach for better diabetes management and reduced complications associated with the disease. These findings have therapeutic implications for managing diabetes mellitus.

Loss of β-catenin reveals a role for glutathione in regulating oxidative stress during cholestatic liver disease.

Cholestasis is an intractable liver disorder that results from impaired bile flow. We have previously shown that the Wnt/β-catenin signaling pathway regulates the progression of cholestatic liver disease through multiple mechanisms, including bile acid metabolism and hepatocyte proliferation. To further explore the impact of these functions during intrahepatic cholestasis, we exposed mice to a xenobiotic that causes selective biliary injury. α-naphthylisothiocyanate (ANIT) was administered to liver-specific knockout (KO) of β-catenin and wild-type mice in the diet. Mice were killed at 6 or 14 days to assess the severity of cholestatic liver disease, measure the expression of target genes, and perform biochemical analyses. We found that the presence of β-catenin was protective against ANIT, as KO mice had a significantly lower survival rate than wild-type mice. Although serum markers of liver damage and total bile acid levels were similar between KO and wild-type mice, the KO had minor histological abnormalities, such as sinusoidal dilatation, concentric fibrosis around ducts, and decreased inflammation. Notably, both total glutathione levels and expression of glutathione-S-transferases, which catalyze the conjugation of ANIT to glutathione, were significantly decreased in KO after ANIT. Nuclear factor erythroid-derived 2-like 2, a master regulator of the antioxidant response, was activated in KO after ANIT as well as in a subset of patients with primary sclerosing cholangitis lacking activated β-catenin. Despite the activation of nuclear factor erythroid-derived 2-like 2, KO livers had increased lipid peroxidation and cell death, which likely contributed to mortality. Loss of β-catenin leads to increased cellular injury and cell death during cholestasis through failure to neutralize oxidative stress, which may contribute to the pathology of this disease.

C60 Fullerene Reduces the Level of Liver Damage in Chronic Alcohol Intoxication of Rats.

The liver is the main organ responsible for the metabolism of ethanol, which suffers significantly as a result of tissue damage due to oxidative stress. It is known that C60 fullerenes are able to efficiently capture and inactivate reactive oxygen species in in vivo and in vitro systems. Therefore, the purpose of this study is to determine whether water-soluble C60 fullerene reduces the level of pathological process development in the liver of rats induced by chronic alcohol intoxication for 3, 6, and 9 months, depending on the daily dose (oral administration; 0.5, 1, and 2 mg/kg) of C60 fullerene throughout the experiment. In this context, the morphology of the C60 fullerene nanoparticles in aqueous solution was studied using atomic force microscopy. Such biochemical parameters of experimental animal blood as ALT (alanine aminotransferase), AST (aspartate aminotransferase), GGT (gamma-glutamyl transferase) and ALP (alkaline phosphatase) enzyme activities, CDT (carbohydrate-deficient transferrin) level, values of pro-antioxidant balance indicators (concentrations of H2O2 (hydrogen peroxide) and GSH (reduced glutathione), activities of CAT (catalase), SOD (superoxide dismutase) and GPx (selenium-dependent glutathione peroxidase)), and pathohistological and morphometric features of liver damage were analyzed. The most significant positive change in the studied biochemical parameters (up to 29 ± 2% relative to the control), as markers of liver damage, was recorded at the combined administration of alcohol (40% ethanol in drinking water) and water-soluble C60 fullerenes in the optimal dose of 1 mg/kg, which was confirmed by small histopathological changes in the liver of rats. The obtained results prove the prospective use of C60 fullerenes as powerful antioxidants for the mitigation of pathological conditions of the liver arising under prolonged alcohol intoxication.

Study on the mechanism of enzymatically treated mulberry (Morus atropurpurea Roxb.) leaf protein relieves liver injury in heat stress rats

Heat stress (HS) can lead to oxidative stress and inflammatory responses, which jeopards animal production. Enzymatically treated mulberry leaf protein (ETMLP) has antioxidant activities and immune regulation. This study aimed to investigate the impacts of ETMLP on mitigate liver injury caused by heat stress in animals. All 25 rats were divided into five groups: control, heat stress, and three ETMLP supplementation groups (HS + 0.4 %, HS + 0.8 %, and HS + 1.2 %). ETMLP supplementation effectively reduced markers of liver damage and increasing the level of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-px). It also regulated protein expression associated with stress response and antioxidant defense and suppressed pro-inflammatory proteins and pathways expression. Moreover, ETMLP improved intestinal morphology and increased the intestinal barrier gene abundance. ETMLP also positively influenced the intestinal microbiota by increasing beneficial microorganisms. Overall, ETMLP reversed heat stress-induced damage, improved growth performance, and regulated the intestinal microbiota in the study animals.

The ameliorative effect of methanol extract of Ricinodendron heudelotii (Baill.) leaves on paracetamol-induced hepatotoxicity in Wistar rats

Plants are a rich source of antioxidants that are produced naturally. Therefore, this study was aimed to evaluate the effect of the plant Ricinodendron heudelotii (Baill.) in the attenuation of paracetamol (PCM) hepatotoxicity in Wistar rats. Twenty-four male albino Wistar rats weighing between 200 and 250 g were divided into four groups, with six rats each. Group 1 served as the control group, receiving just distilled water. Groups 2 and 3 received orally 250 mg/kg bwt/day PCM and 300 mg/kg bwt/day methanol extract of Ricinodendron heudelotii (Baill.) leaves for two weeks, respectively. For group 4, the Ricinodendron heudelotii (Baill.) leaf extract was pre-administered for 1 week before receiving 300 mg/kg bwt/day Ricinodendron heudelotii (Baill.) leaves extract and 250 mg/kg bwt/day PCM for 2 weeks. As a marker of liver damage, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Liver tissue reduced glutathione (GSH) concentration, superoxide dismutase (SOD), glutathione-S-transferase (GST), and catalase activities were utilized to determine antioxidant state, while malondialdehyde (MDA) concentration was employed as a lipid peroxidation indicator. When compared to the control group, the activities of serum AST, ALT, SOD, and MDA levels were considerably (p < 0.05) higher in the PCM group, although GSH level and GST and catalase activities were significantly lower. In comparison to the PCM group, co-administration of PCM with Ricinodendron heudelotii (Baill.) extract decreased serum AST and ALT activities. This study shows that the leaf extracts of Ricinodendron heudelotii (Baill.) protects Wistar rats’ livers from PCM-induced oxidative stress by increasing antioxidant enzymes.

Oat protein modulates cholesterol metabolism and improves cardiac systolic function in high fat, high sucrose fed rats.

Oats are recognized to provide many health benefits that are mainly associated with its dietary fibre, β-glucan. However, the protein derived from oats is largely understudied with respect to its ability to maintain health and attenuate risk factors of chronic diseases. The goal of the current study was to investigate the metabolic effects of oat protein consumption in lieu of casein as the protein source in high fat, high sucrose (HF/HS) fed Wistar rats. Four-week-old rats were divided into three groups and were fed three different experimental diets: a control diet with casein as the protein source, an HF/HS diet with casein, or an HF/HS diet with oat protein for 16 weeks. Heart structure and function were determined by echocardiography. Blood pressure measurements, an oral glucose tolerance test, and markers of cholesterol metabolism, oxidative stress, inflammation, and liver and kidney damage were also performed. Our study results show that incorporation of oat protein in the diet was effective in preserving systolic heart function in HF/HS fed rats. Oat protein significantly reduced serum total and low-density lipoprotein cholesterol levels. Furthermore, oat protein normalized liver HMG-CoAR activity, which, to our knowledge, is the first time this has been reported in the literature. Therefore, our research suggests that oat protein can provide hypocholesterolemic and cardioprotective benefits in a diet-induced model of metabolic syndrome.