Decrease In ALT Research Articles

Antifibrotic potential of Reserpine (alkaloid) targeting Keap1/Nrf2; oxidative stress pathway in CCl4-induced liver fibrosis.

The death rate due to liver cancer approaches 2 million annually, the majority is attributed to fibrosis. Currently, there is no efficient, safe, non-toxic, and anti-fibrotic drug available, suggesting room for better drug discovery. The current study aims to evaluate the anti-fibrotic role of reserpine, an alkaloid plant compound against CCl4-induced liver fibrosis. In-silico docking analysis showed the interaction of reserpine with keap1 protein with the binding energy -9.0 kcal/mol. In-vitro, biochemical analysis, anti-oxidative indexes, and inflammatory cytokines analysis were performed in HepG2 cells. The non-toxic nature of the compound (<100μg/ml) was evaluated through MTT assay in HepG2 and Vero cell lines. The antifibrotic potential of the reserpine compound (dose of 0.5mg/kg) was assessed in CCl4-administered C57BL/6J mice models. Hematoxylin & Eosin and Masson staining were performed to study the morphological changes of liver tissues. Immune histochemistry (IHC) analysis was performed to evaluate the effect of reserpine on the liver fibrosis marker. The biochemical assay indicated a significant decrease in ALT, AST, and MDA levels and increased catalase enzyme post-6-week reserpine treatment in mice models. Gene expression analysis revealed that the reserpine targets oxidative stress Keap1/Nrf2 pathway and down-regulated Keap1 expression by 5-fold and up-regulated Nrf2 and Nqo1 expression by 6 and 4.5-fold respectively showing its antioxidant response. It suppressed the expression of Cyp2e1 by 2.2-fold, illustrating the compound's ability to block lipid peroxidation. Histological and immunostaining exhibited improved hepatocyte morphology and reduced collagen deposition in liver tissues due to reserpine. Reserpine treatment lowered the fibrotic markers α-SMA and Col-1 by 1.3 and 1.5 folds respectively as compared to the control group and increased the expression of miR-200a and miR-29b by 15.5 and 8.2 folds (p<0.05) while decreased miR-128-1-5p expression by 5-fold. A comprehensive In-silico, In-vitro, and In-vivo analysis revealed that reserpine has a strong anti-fibrotic effect against the CCl4-induced liver fibrosis in C57BL/6J mice model by targeting the Keap1/Nrf2 pathway.

Metabolic and bariatric surgery in adolescents: a single-center study of efficacy and outcome predictors.

Some adolescents undergoing metabolic and bariatric surgery (MBS) have suboptimal responses to surgery, particularly over the longer term. This study aimed to quantify changes in weight loss over time in adolescents undergoing MBS and identify preoperative predictors of weight loss. This was a prospective, observational cohort study of 73 adolescents (12-19 years) living with obesity undergoing MBS. Absolute and relative changes in anthropometric and biochemical parameters were evaluated up to 30 months. Changes in anthropometric measures were assessed using a mixed residual maximal likelihood model. Univariable and multivariable logistic regression were used to identify predictors of a >35.0% reduction in BMI z-score from baseline to 12 months. Predictive accuracy was assessed by ROC-AUC analysis. Most patients (87.7%) underwent laparoscopic sleeve gastrectomy (12.3% underwent laparoscopic sleeve bypass). Weight, weight z-score, BMI, and BMI z-score significantly decreased over 30 months (p<0.001) up to a -53.8% relative change in BMI z-score at 30 months. There was a significant increase (p=0.02) in HDL cholesterol and a significant decrease in triglycerides (p=0.0001) and ALT (p=0.0004) after surgery. A higher preoperative BMI was associated with a reduced odds (OR 0.89, 95%CI 0.79-0.97, p=0.03) of a >35% reduction in BMI z-score at 12 months. A baseline BMI >52.6 kg/m2 had a sensitivity of 100% and specificity of 40.6% for detecting a >35.0% postoperative decrease in BMI z-score. MBS results in sustained weight loss in adolescents. A high preoperative BMI predicts resistance to optimal weight loss after surgery and argues against delaying surgery once eligibility thresholds are met.

Longitudinal response to standard of care in pediatric metabolic dysfunction-associated steatotic liver disease: Rates of improvement and worsening, and factors associated with outcomes.

Longitudinal outcomes in children with metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear due to the absence of a standardized monitoring approach. This study aimed to 1) define improvement and worsening in children with MASLD, 2) estimate rates of improvement or deterioration with standard of care (SOC) over one and two years, and 3) identify baseline and longitudinal factors associated with improvement or worsening. Using data from two large randomized controlled trials, we derived definitions for composite improvement and worsening of MASLD based on associations between changes in ALT, GGT, and liver histology after one and two years. Improvement was defined as ≥40% decrease in ALT and ≥20% decrease in GGT and worsening as ≥20% increase in both ALT and GGT. We applied definitions to a cohort of 440 children with MASLD. After one year of SOC, 22% of children with MASLD showed improvement, increasing to 31% after two years. However, 20% showed worsening after both one and two years despite receiving SOC. Logistic regression analysis, employing stepwise model selection, identified changes in body mass index (BMI) z-score and cholesterol to be most associated with improvement or deterioration. This study developed criteria for improvement and worsening in children with MASLD over one and two years of follow-up. With SOC, over one-quarter of children are likely to improve while one-fifth of children are likely to worsen. Targeting interventions that affect BMI and lipid parameters may help improve MASLD over time.

Use Of Glutathione As An Additional Supplement For The Treatment Of Fatty Liver Disease : A Systematic Review

Introduction : The liver normally contains fat tissue, but if it exceeds 5% of the liver weight, this condition is called fatty liver disease. Fatty liver disease is divided into two major groups, namely : Alcoholic Fatty Liver Disease (AFLD) and Non-Alcoholic Fatty Liver Disease (NAFLD). Fatty liver disease can potentially progress to liver cirrhosis, and this can be prevented by antioxidants, through their anti-inflammatory actions. Glutathione is a potent antioxidant, and naturally produced in our body, with the highest level in the liver, which is the main organ in the detoxification process. This study aimed to systematically review the importance of Glutathione as an adjunct supplement for the treatment of fatty liver disease, which is one of antioxidants, can help with fatty liver problems. Methods : This study applied a Systematic Review approach, that included published articles with Randomized Controlled Trials (RCTs). We searched these articles in two electronic databases, namely Google Scholar and PubMed. Based on the search, 1.141 cases of fatty liver were found and the author determined 2 (two) relevant literature/studies that focus on this research. Results : Based on 2 studies with a total of 208 patients and divided into 2 groups, namely the intervention group and the control group, it was found that the group that was intervened with glutathione supplementation for at least 3 months experienced a decrease in CAP, ALT, and IMT values. Especially if coupled with MHD/improved healthy lifestyle, the recovery process of fatty liver conditions can take place faster. Conclusions : Glutathione as an antioxidant and acts as a hepatoprotector, demonstrated the ability to potentially hold the progression of NAFLD, and improve liver function. The presence of MHD/improve healthy lifestyle synergized the efficacy of Glutathione against the progression of NAFLD.

The impact of apple cider vinegar on nonalcoholic fatty liver disease in rainbow trout, Oncorhynchus mykiss: A study of therapeutic potential and health benefits

AbstractIn this study, we aimed to experimentally induce fatty liver disease in rainbow trout, Oncorhynchus mykiss, and then assessed the illness recovery process, growth, and changes in the expression of FAAH and ACADL genes in both healthy (0 [C2] and 4% apple cider vinegar [T4]) and diseased fish (0 [C1], 1 [T1], 2 [T2], and 4% [T3]) apple cider vinegar. To conduct the study, 180 rainbow trout were randomly assigned to six different experimental treatments, each with three replications. The investigation lasted for 60 days. Growth indices, liver histology, blood biochemical parameters, and transcription of the ACADL and FAAH genes in the liver tissue were measured. The study found no significant differences in the final weights across all the treatments. Apple cider vinegar (ACV) administration resulted in a decrease in AST, ALT, and ALP; however, these values did not show a significant difference from C2. In T3, triglycerides significantly decreased (p &lt; 0.05), whereas in T4, triglycerides significantly increased (p &lt; 0.05). Hepatocytes from ACV‐containing treatments showed reduced fat compared with T4 and the control group (C1). While there was a significant difference (p &lt; 0.05) in the expression of the FAAH gene, there was no significant difference (p &gt; 0.05) in the expression of the ACADL gene between experimental treatments. The findings of our study indicate that an inclusion of up to 2% ACV may have positive effects on trout aquaculture and NAFLD treatment.

Evaluation of the efficiency of the hepatoprotector glucuronate in toxic hepatitis of various etiology

The objective was to study the effectiveness of the use of hepatoprotector glucuronate at the early stage of intensive therapy of toxic hepatitis of various etiologies.Materials and methods. We studied 120 patients with toxic hepatitis who were treated at the Republican research center for emergency medicine in 2022–2023. The study was carried out in two groups of patients. Group I – 60 patients admitted in 2023, who, in addition to traditional therapy, received a complex hepatoprotector glucuronate (Jetepar®)*. Group II (comparison group) – 60 patients who applied in 2022 and received only traditional therapy. Biochemical blood parameters were studied upon admission and over time on day 5. The severity of intellectual impairment was assessed using cognitive scales and the Reitan test on days 2 and 5 from the start of treatment.Results. Upon admission, both groups showed signs of toxic liver damage. In dynamics by the 5th day in patients of group I, there was a decrease in ALT by 63.7%, AST by 66.4%, alkaline phosphatase by 54.2% from the initial values, which was 3.9 and 2.6, 2. 1 lower than in the comparison group. The level of free ammonia in patients of group I on the 5th day decreased by 52%, and lactate by 57% from the initial level, almost to the physiological norm, while in the comparison group (II) only by 24.8% and 38.1%, which was 2.2 and 1.5 times worse than in the main group. Screening of the level of intelligence using two cognitive scales and the Reitan test showed that in patients in the comparison group, cognitive function indicators on the 5th day were 1.4, 1.5 and 1.2 times lower than in the main group.Conclusion. The use of the hepatoprotector glucuronate improves liver parameters and cognitive functions in patients with toxic hepatitis.

Vitamin U alleviates AFB1-induced hepatotoxicity in pregnant and lactating mice by regulating the Nrf2/Hmox1 pathway

This study investigated the protective effect of Vitamin U on liver injury induced by aflatoxin B1 (AFB1) in maternal mice. 25 pregnant ICR mice were randomly divided into five groups: the AFB1 group (AF, 0.3 mg AFB1/kg b.w.), the Vitamin U group (U, 50 mg Vitamin U/kg b.w.), the AFB1 + Vitamin U group (AU, 50 mg Vitamin U /kg b.w. + 0.3 mg AFB1/kg b.w.), the control group (DMSO), and the MOCK group (distilled water). They were administered substances by gavage every day for 28 days. Results indicated that exposure to AFB1 increased the liver index and caused histological disruptions. Elevated serum levels of ALT and ALP were observed, along with a significant increase in liver MDA content and a decrease in GSH-Px and T-SOD levels. Moreover, the Keap1 and Hmox1 gene was downregulated with statistical significance, while the IL1β and TNFα gene were significantly upregulated. Vitamin U was demonstrated by the organized structure of liver cells in tissue slices, effectively reducing liver cell necrosis. This intervention was associated with a significant decrease in serum ALT and ALP activities, as well as a significant decrease in liver MDA content. Additionally, there were significant increases in liver T-SOD and GSH-Px levels, along with upregulation of mRNA and protein expression of Nfr2, Hmox1 and Keap1, and downregulation of mRNA expression of the IL1β gene. In summary, Vitamin U mitigated oxidative stress-induced liver injury by modulating the Nrf2/Hmox1 signaling pathway and inflammatory factors affected by AFB1.

Evaluation of concurrent use of Vitamin C and Niclosamide against methotrexate-induced liver injury in mice.

To examine the effect of using vitamin C and niclosamide together on liver damage caused by methotrexate. The study was conducted at the Pharmacology Department and the Iraqi Center for Cancer and Medical Genetics Research, College of Medicine, Mustansiriya University, Baghdad, Iraq, from November 2020 to July 2021, and comprised albino mice who were randomly assigned to 5 groups. Group 1 comprised controls, groups 2 to 5 was received methotrexate, niclosamide 70mg/kg/day, vitamin C 100mg/kg/day, and a combination of niclosamide and vitamin C, respectively. Mice in groups 3, 4 and 5 also received an intraperitoneal injection of methotrexate 20mg/kg to induce hepatotoxicity. After 48 hours of the injection, the mice were sacrificed under chloroform anaesthesia. Cardiac blood samples were drawn for biochemical examination. The liver, after being washed, was divided into two parts; one part was taken for histological examination, and the other was preserved in formalin 10% for histopathological analyses. Data was analysed using SPSS 16. Of the 35 mice, there were 7(20%) in each of the 5 groups. The overall age ranged between 9-12 weeks and weight between 18-38gm. The results show significant hepatoprotection ( p-value <0.05) produced by both niclosamide and Vitamin C separately, reflected by a decrease in ALP, ALT, and LDH, while the combination of (niclosamide and Vitamin C) showed no additive effect (p>0.05) on enhancement of liver function. Niclosamide alone was found to be superior than in combination with vitamin C for treating methotrexate-induced liver damage.

Peptidergic and adenosinergic drugs administration to comatose patients caused by alcohol consumption on early hospital period

Introduction. Medical care for patients diagnosed with the toxic effect of ethanol (according to ICD-10 code T51.0) it turns out to be in specialized toxicological centers or in emergency departments of multidisciplinary hospitals. The purpose of this study was to study the effectiveness of the drug моликсан® (molixаn) at different levels of medical care for patients diagnosed with the toxic effect of ethanol. Material and method. 128 patients were included in the study, of which 76 patients were taken to the emergency department of St. Petersburg State Medical Institution "Alexandrovskaya Hospital" and 52 patients were taken to the intensive care unit No. 11 of the St. Petersburg Scientific Research Institute of Emergency Medicine named after I.I. Dzhanelidze. All patients met the inclusion criteria: age 18–60 years; impaired consciousness of alcoholic genesis 21–30 points on the Glasgow–Pittsburgh coma scale (PBSS: Pittsburg Brain Stem Score, Kelsey S.F., et al. 1991); ethanol concentration in the blood is more than 2.5%. 72 patients were included in the моликсан® group, 56 patients in the Placebo group. Results. The use of the drug моликсан® has a positive effect on the dynamics of restoring the level of consciousness, which is reflected in higher values of the Glasgow–Pittsburgh scale after 1, 3 and 6 hours from the start of therapy (p&lt;0.01), reducing the period of stay of the patient in a coma from 150 [75; 178] minutes to 60 [50; 161.5] minutes (p&lt;0.05) and restoration of consciousness to a clear level after 3.5± 0.3 hours (p&lt;0.05).It was also revealed, that in the group of patients using моликсан®, normalization of heart rate (p&lt;0.05) and a decrease in the frequency and severity of tremor (p&lt;0.05) were noted. The hepatoprotective efficacy of моликсан® was shown, which manifested itself in a decrease in ALT, AST, GGTP, alkaline phosphatase, total and direct bilirubin (p&lt;0.001). Limitations. The clinical efficacy of моликсан® in the toxic effects of severe ethanol was carried out in patients with depression of consciousness and elevated levels of ALT, AST, GGTP, alkaline phosphatase, total and direct bilirubin, which indicated the presence of alcoholic hepatopathy. Conclusion. The conducted study showed the expediency of using моликсан® at a dosage of 3.0 mg/kg intravenously with the toxic effect of ethanol of moderate and severe severity of the disease.

Effect of sodium glucose Co-transporter 2 inhibitor use on anthropometric measurements and blood glucose in obese and non-obese type 2 diabetic patients

Obesity and type 2 diabetes mellitus are closely associated with each other and require careful management. This study aimed to assess the impact of sodium-glucose co-transporter 2 (SGLT2) inhibitors on glycemic control and body composition in diabetic patients, stratified by obesity status. We enrolled patients diagnosed with type 2 diabetes mellitus, categorized as obese (BMI≥30) or non-obese (BMI<30), from our outpatient clinic. SGLT2 inhibitor therapy was added to their existing treatment regimen without altering dietary habits or exercise routines. Anthropometric measurements and laboratory parameters were compared between baseline and the third month of treatment. The study included 40 participants, evenly split between obese and non-obese groups. At the third-month follow-up, significant reductions were observed in BMI, weight, waist and hip circumference, and body fat percentage across both groups (p<0.001). Conversely, muscle mass percentage significantly increased (p<0.001). Additionally, there were statistically significant decreases in HbA1c, glucose, CRP, ALT, LDL, and total cholesterol levels from baseline to the third month of treatment (p<0.001 for HbA1c and glucose; p=0.009, p=0.022, p=0.003, and p=0.021, respectively, for CRP, ALT, LDL, and total cholesterol). The findings of the present study suggest that SGLT2 inhibitors may offer substantial benefits, particularly in the management of obesity-related type 2 diabetes.

Effect of sainfoin (Onobrychis viciifolia Scop.) seed-based diet on rats: A comprehensive evaluation of hemogram, biochemistry, and histopathology.

Sainfoin species (Onobrychis spp.) have been employed for centuries as an essential forage for ruminant animals, both for grazing and as hay. The seeds produced by sainfoin have also been investigated as an animal feed source and were indicated to be a particularly protein-rich supplement for monogastric animals. This study explores the effects of two sainfoin seed inclusion rates in rat diets compared to a control diet, focusing on blood biochemical parameters and a comprehensive histopathological evaluation of multiple organ systems. Thus, we provide a novel contribution to the body of evidence investigating sainfoin seeds as a protein supplement in monogastric animal diets. In this 21-day experiment, seven rats each were assigned to the control group, a 5% sainfoin seed group, and a 10% sainfoin seed group. The control group received standard feed and water; the second group received feed with 5% sainfoin seeds; and the third group received feed with 10% sainfoin seeds. At the experiment's end, necropsies and evaluations were conducted. Histopathological exams revealed normal organ structures in all 21 samples, regardless of the group. Blood analysis showed statistically significant decreases in creatine, ALT, P, Ca, and Mg levels in the sainfoin seed groups compared to the control group, with most values nearing reference levels, suggesting potential benefits. Notably, no adverse effects were observed when sainfoin seeds were included at 5% and 10% in the rat feed. These findings contribute to a growing body of research investigating the inclusion of sainfoin seeds in monogastric animal diets, which is a foundational component of assessing sainfoin's potential as a novel pulse crop for human consumption.

Association between BMI Change, Transaminases, and Other Metabolic Parameters in Children with Nonalcoholic Fatty Liver Disease.

Weight loss and lifestyle interventions are the mainstay of treatment in pediatric NAFLD. There are gaps in the literature on the objective improvement in BMI to meaningfully impact NAFLD in children. To determine the decrease in BMI associated with a significant decline in ALT and other metabolic parameters. Retrospective chart review of pediatric patients with the diagnosis of NAFLD. Data were collected at the baseline and 6 and 12 months. A linear regression model was used to assess the percent change in BMI predictive of change in ALT and other metabolic parameters. 281 charts were included. 71% of patients who had up to a 2.5% loss in BMI at 6 months had a decrease in ALT of up to 10 U/L compared to 43% patients who did not have a decrease in BMI up to 2.5% loss at the same time period (P=0.01). The linear regression model showed that 6-month and 12-month percent changes in BMI are predictive of 6-month and 12-month ALT changes (P=0.01 and 0.02), respectively. ALT normalization was achieved on 12% of patients with a ≥2.5% decrease in BMI at 6 months compared to 1% of patients that had no decrease of ≥2.5% decrease in BMI at 6 months (P=0.01). The mean BMI Z-score decline was 0.18 (P=0.001) in the group with a ≥2.5% decrease in BMI at 6 months. BMI loss of up to 2.5% and the mean BMI Z-score 0.18 are associated with a significant decrease in ALT of up to 10 U/L. BMI percent change at 6 months and 12 months is predictive of changes in ALT. These results should help guide providers in clinical practice set objective goals for the management of children with NAFLD resulting from obesity.

Aminotransferases activity on additional therapy in rheumatoid arthritis patients with liver disease.

&lt;b&gt;Aim&lt;/b&gt;&lt;b&gt;.&lt;/b&gt; Investigate the effect of additional therapy of atorvastatin, essential phospholipids and their combination on activity of aminotransferases in RA patients with NAFLD.&lt;br /&gt; &lt;b&gt;Materials and Methods.&lt;/b&gt; We investigated 126 RA patients and 30 in control. 77 RA patients with NAFLD were divided into three groups. I: 25 RA patients received 10 mg of atorvastatin per day. II: 26 RA patients received essential phospholipids 1800 mg per day. III: 26 RA patients received essential phospholipids 1800 mg per day and atorvastatin 10 mg per day for 6 months.&lt;br /&gt; &lt;b&gt;The results.&lt;/b&gt; In the I group, a transient increase in ALT and AST activity was observed to 35.11±3.501 U/l and 30.51±2.19 U/l, respectively, and a spontaneous decrease in elevated transaminases was recorded after 6 months of atorvastatin use. In the II group, a decrease in ALT by 25.6% was observed compared to the indicators before treatment, and they remained unchanged even after 6 months. After 3 months of complex use of atorvastatin and essential phospholipids, ALT activity decreased by 33.8% and AST decreased by 8.2%, which was not observed in RA patients with NAFLD of groups I and II.&lt;br /&gt; &lt;b&gt;Conclusions.&lt;/b&gt; Use essential phospholipids 600 mg three times a day and atorvastatin 10 mg per day for 6 months in addition to antirheumatic therapy in RA patients with NAFLD allows to avoid a transient increase in aminotransferases, reduce the severity of hepatotoxic reactions, and avoid stopping or canceling antirheumatic therapy.

A Comparison of the Protective Effect of Pyridoxine and N-Acetylcysteine in Paracetamol Induced Hepatotoxicity in Rats

Paracetamol is a common over the counter drug. Paracetamol-induced hepatotoxicity results in over 300,000 hospitalizations each year and accounts for up to 42% of all cases of acute liver failure. N-acetylcysteine (NAC) is a potential antidote to manage paracetamol toxicity. Objective: To investigate the effects of pyridoxine, alone and in combination with NAC in repairing paracetamol-induced liver damage in male Wister rats. Methods: A single oral dose of paracetamol (650 mg/kg) was administered to Wistar rats to induce hepatotoxicity. The hepato-protective effects of NAC at a dose 300 mg/kg, and pyridoxine (200 mg/kg) were evaluated using standard liver function tests and histopathological along with serum glutathione levels. Results: The administration of pyridoxine and NAC resulted in a significant decrease in AST, ALT, and total bilirubin levels and the reversal of histopathological changes. Conversely, administering NAC and pyridoxine in combination yielded significant changes except for the glutathione level. Conclusions: The study concluded that pyridoxine may be used as a potential hepatoprotective drug in paracetamol-induced hepatotoxicity. In combination with NAC, it showed protective effects in paracetamol-induced hepatoxicity.

Effects of vitamin D supplementation on liver fibrogenic factors, vitamin D receptor and liver fibrogenic microRNAs in metabolic dysfunction-associated steatotic liver disease (MASLD) patients: an exploratory randomized clinical trial

Background and aimsMetabolic dysfunction-associated steatotic liver disease (MASLD) is a global metabolic problem which can lead to irreversible liver fibrosis. It has been shown that vitamin D and its receptors contribute to fibrogenic pathways in the liver. However, the effect of vitamin D supplementation on liver fibrosis related factors have not been examined. This double blinded placebo controlled clinical trial was designed to investigate the effects on vitamin D supplementation on serum levels of VDR, fibrogenic factors and fibrogenic MicroRNAs in MASLD patients.MethodsForty six MASLD patients after block matching for sex and BMI were randomly assigned to receive 4000 IU/d vitamin D or placebo for 12 weeks. Weight, height and waist circumference were measured. Serum fibrogenic microRNAs, laminin, collagen type IV, hyaluronic acid, vitamin D, VDR, PTH, blood fasting glucose, serum fasting insulin, lipid profile, ALT and AST were determined at the baseline and at the end of the trial. Insulin resistance and insulin sensitivity were calculated using the HOMA-IR and QUICKI equation.ResultsSupplementation with vitamin D for 12 weeks led to the significant increases in serum 25(OH) vitamin D, VDR and HDL-C compared to placebo (P < 0.001, P = 0.008 and P < 0.001). There were significant decreases in ALT, AST, FBS and LDL-C levels in the vitamin D group as compared to the placebo (P < 0.05). Laminin and hyaluronic acid concentrations were significantly decreased in the vitamin D group as compared to the placebo group, by -10.6 and − 28.7 ng/mL, respectively. Supplementation with vitamin D for 12 weeks resulted in a significant lower MiR-21 and MiR-122 gene expressions compared to the placebo group (P = 0.01 and P < 0.001, respectively).DiscussionAs the first randomized controlled trial on the effect of vitamin D supplementation on serum levels of VDR, fibrogenic factors and fibrogenic MicroRNAs in MASLD patients, we found a significant reduction in some liver fibrogenic factors, in liver transaminases and corresponding changes in some fibrosis-related MiRs and some metabolic factors. Further clinical trials with larger sample sizes and direct measures of liver fibrosis are needed to confirm these findings.Trial registration number(available at: http://www.irct.ir, identifier: IRCT201405251485N13), Registration date: 14-03-2017.

Total saponins of Panax japonicus alleviates CCl4-induced acute liver injury in rats by regulating the PI3K/AktNF-κB signaling pathway

To investigate the protective effect of total saponins of Panax japonicus (TSPJ) against CCl4-induced acute liver injury (ALI) in rats and explore the underlying pharmacological mechanisms. Male SD rat models of CCl4-induced ALI were given intraperitoneal injections of distilled water, 100 mg/kg biphenyl bisabololol, or 50, 100, and 200 mg/kg TSPJ during modeling (n=8). Liver functions (AST, ALT, TBil and ALP) of the rats were assessed and liver pathologies were observed with HE staining. Immunohistochemistry was used to detect the expressions of PI3K/Akt/NF-κB signaling pathway molecules in liver tissue; ELISA was used to determine the levels of T-SOD, GSH-Px, and MDA. Western blotting was performed to detect the expression levels of PI3K-Akt and SIRT6-NF-κB pathways in the liver tissue. Network pharmacological analysis indicated that the key pathways including PI3K/Akt mediated the therapeutic effect of TSPJ on ALI. In the rat models of ALI, treatments with biphenyl bisabololol and TSPJ significantly ameliorated CCl4-induced increase of serum levels AST, ALT, ALP, TBil and MDA and decrease of T-SOD and GSH-Px levels (all P < 0.01). The rat models of ALI showed significantly increased expression of p-NF-κB (P < 0.01), decreased expressions of PI3K, p-Akt and SIRT6 proteins, and elevated expression levels of p-NF-κB, TNF-α and IL-6 proteins in the liver, which were all significantly improved in the treatment groups (P < 0.05 or 0.01). TSPJ can effectively alleviate CCl4-induced ALI in rats by suppressing inflammatory responses and oxidative stress in the liver via regulating the PI3K/Akt and SIRT6/NF-κB pathways.

Supplementation of Nutraceuticals from Dwarf Kiwi and Apple Improves Lipid Profile in Overweight Adults

(1) Background: Overweight and obesity are emerging global problems causing multiple health complications. Excessive fat tissue content leads to chronic inflammation, which is why antioxidative compounds that could potentially reduce these processes are possible agents that could be supplemented in order to prevent metabolic complications of overweight and obesity. Apples and dwarf kiwis are good sources of antioxidative agents such as quercetin and chlorogenic acid. The aim of this study was to assess if apple and dwarf kiwi nutraceutical supplementation can improve the metabolic parameters of overweight adults. (2) Methods: 43 participants were enrolled in the double-blinded pilot study: 21 in the supplementation group and 22 in the placebo group. The one 1000 mg nutraceutical capsule contained 10% Chopin apple peel extract, 10% whole dwarf kiwi fruit extract, 75% Chopin apple core extract, and 5% rapeseed peptides. The supplementation group received two capsules/day for 60 days. (3) Results: The supplementation of the apple and kiwi product resulted in a lowering of ALT in the supplementation group (from 29.65 ± 19.02 UI/L to 23.80 ± 13.76 UI/L; p = 0.01). Subgroup analysis in men and women showed a significant decrease in total cholesterol level (from 220.15 ± 36.69 mg/dL to 208.43 ± 37.09 mg/dL; p = 0.04), non-HDL cholesterol (from 161.17 ± 41.00 mg/dL to 145.69 ± 41.75 mg/dL; p = 0.02) and ALT (from 25.41 ± 12.05 UI/L to 19.07 ± 6.13 UI/L; p = 0.01) in women and triglycerides levels (from 212.74 ± 127.15 mg/dL to 155.63 ± 80.61 mg/dL; p = 0.047) in men. (4) Conclusions: The supplementation of nutraceuticals from apples and dwarf kiwi led to improvements in lipid profile. It can be a possible new agent for counteracting overweight metabolic complications, however, larger group studies and more detailed tests are needed to support these preliminary findings.

Suppression of TGF-β/Smad3 signaling pathway by Capparis spinosa and quercetin in a rat model of nonalcoholic steatohepatitis.

Liver diseases, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), pose significant global public health challenges. This study investigates the therapeutic effects of quercetin (QC), Capparis spinosa (CS), a QC and CS combination, and Saroglitazar (SARO) on NASH in a Wistar rat model. NASH was induced by a 42-day high-fat diet regimen in male Wistar rats. Post-induction, rats were divided into five groups receiving SARO, QC, CS, and CS+QC combination. We monitored changes in liver and body weights and evaluated the expression of genes associated with fatty acid biosynthesis (e.g., ACC and FAS), β-oxidation (e.g., CPT1, PPAR α), inflammation (e.g., TNF-α and IL-6), and fibrosis (e.g., TGF-β and COL1A), as well as protein expression levels of p-Smad2/3 and p-Smad3. Treatment with QC+CS significantly decreased liver weight, body mass gain, and liver triglyceride (TG) compared to other treatments. The QC and CS combined therapy also resulted in a greater normalization of hepatic enzymatic activities, including decreases in ALT and AST levels, coupled with improvements in lipid profile indicated by decreased LDL-C and increased HDL-C concentrations, as compared to SARO and QC alone. Furthermore, this combined treatment significantly down-regulated the expression of TGF-β, TNF-α, IL-6 genes, and Smad2/3 and Smad3 protein levels. Our study demonstrates that an interactive effect between QC and CS can effectively reduce liver fibrosis and steatosis by inhibiting the TGF-β/Smad3 signaling pathway in a diet-induced model of nonalcoholic steatohepatitis and fibrosis in rats.

Ameliorative potential role of Rosmarinus officinalis extract on toxicity induced by etoposide in male albino rats.

The present work was showed to assess the effect of administration of rosemary extract on etoposide-induced toxicity, injury and proliferation in male rats were investigated. Forty male albino rats were arranged into four equal groups. 1st group, control; 2nd group, etoposide; 3rd group, co-treated rosemary & etoposide; 4th group, rosemary alone. In comparison to the control group, etoposide administration resulted in a significant increase in serum ALT, AST, ALP, total bilirubin, total protein, and gamma GT. In contrast; a significant decrease in albumin level in etoposide group as compared to G1. G3 revealed a significant decrease in AST, ALT, ALP, total protein and total bilirubin levels and a significant rise in albumin level when compared with G2. Serum levels of urea, creatinine, potassium ions, and chloride ions significantly increased; while sodium ions were significantly decreased in G2 when compared with G1. Also, there was an increase of MDA level for etoposide treated group with corresponding control rats. However, there was a remarkable significant decrease in SOD, GPX and CAT levels in G2 as compared to G1. There was a significant increase in serum hydrogen peroxide (H2O2) and Nitric oxide (NO) levels in group treated with etoposide when compared to control group. It was noticeable that administrated by rosemary alone either with etoposide had not any effect on the levels of H2O2 and Nitric oxide. Serum level of T3 and T4 was significantly increased in etoposide-administered rats in comparison with G1. The administration of rosemary, either alone or with etoposide, increased the serum levels of T3 and T4 significantly when compared to control rats. The gene expression analysis showed significant downregulation of hepatic SOD and GPx in (G2) when compared with (G1). The treatment with rosemary extract produced significant upregulation of the antioxidant enzymes mRNA SOD and GPx. MDA gene was increased in (G2) when contrasted with (G1). Treatment of the etoposide- induced rats with rosemary extract delivered significant decrease in MDA gene expression when compared with etoposide group. Rats treated with etoposide showed significant decline in hepatic Nrf2 protein expression, when compared with G1. While, supplementation of Etoposide- administered rats with the rosemary produced a significant elevation in hepatic Nrf2 protein levels. Additionally, the liver histological structure displayed noticeable degeneration and cellular infiltration in liver cells. It is possible to infer that rosemary has a potential role and that it should be researched as a natural component for etoposide-induced toxicity protection.

Hepatoprotective Effects of Medicinal Honey: Introducing a New Classification Based on Phenolic Content and Antioxidant Capacity

Honey contains vital compounds capable of ameliorating oxidative stress damage. Two markers of total phenolic content (TPC) and antioxidant capacity (TAC) have been selected for the classification of honey samples for investigating the protective effects of different honey samples on hepatotoxicity induced by CCl4. Hence, 56 male Wistar rats in 8 groups were selected and were given a daily single dose (20%) of honey samples classified as weak, medium, and strong based on TPC and TAC. After four weeks of pretreatment, acute liver damage (ALD) was induced in treated groups using CCl4 mixed with corn oil in a 1:1 ratio. Following ALD induction, the animals were sacrificed. Various samples were then collected for analysis, including serum samples for biochemistry tests (ALT, AST, ALP, and FBS) and antioxidant status assessment (DPPH, FRAP, THIOL, and MDA); urine samples for antioxidant status evaluation (DPPH, FRAP, and MDA); liver tissue homogenate for oxidative stress marker analysis (SOD, CAT, GPx, and MDA); and tissue samples for histopathological examination. Biochemical results showed a significant decrease (p ≤ 0.05) in ALT, AST, ALP, and FBS values in ALD groups treated with honey; antioxidant and oxidative stress evaluations also exactly approved the same results by an insignificant decrease (p ≥ 0.05) in serum MDA and a significant increase (p ≤ 0.05) in THIOL and DPPH and also a reduction in urinary MDA and increase of urinary DPPH all compared to positive control (p ≤ 0.05). SOD, CAT, and GPx activities and MDA values in liver homogenate also ameliorated in honey‐treated group (p ≤ 0.05). Histopathological evaluations confirmed less damage in treated groups, especially in stronger honey. Potent honey samples based on TPC and TAC have more protective effects in hepatotoxicity.