Hepatoprotective effects of leaf extract of Annona senegalensis against aflatoxin B1 toxicity in rats.

Global aflatoxin contamination of agricultural commodities is of the most concern in food safety and quality. This study investigated the hepatoprotective effect of 80% methanolic leaf extract of Annona senegalensis against aflatoxin B1 (AFB1)-induced toxicity in rats. A. senegalensis has shown to inhibit genotoxicity of aflatoxin B1 in vitro. The rats were divided into six groups including untreated control, aflatoxin B1 only (negative control); curcumin (positive control; 10 mg/kg); and three groups receiving different doses (100 mg/kg, 200 mg/kg, and 300 mg/kg) of A. senegalensis extract. The rats received treatment (with the exception of untreated group) for 7 days prior to intoxication with aflatoxin B1. Serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, and creatinine were measured. Hepatic tissues were analysed for histological alterations. Administration of A. senegalensis extract demonstrated hepatoprotective effects against aflatoxin B1-induced toxicity in vivo by significantly reducing the level of serum aspartate aminotransferase and alanine aminotransferase and regenerating the hepatocytes. No significant changes were observed in the levels of alkaline phosphatase, lactate dehydrogenase, and creatinine for the AFB1 intoxicated group, curcumin+AFB1 and Annona senegalensis leaf extract (ASLE)+AFB1 (100 mg/kg, 200 mg/kg, and 300 mg/kg body weight [b.w.]) treated groups. Annona senegalensis is a good candidate for hepatoprotective agents and thus its use in traditional medicine may at least in part be justified.Contribution: The plant extract investigated in this study can be used in animal health to protect the organism from toxicity caused by mycotoxins.

Screening of Platycodonis Radix Fractions for Antiobesity Activities and Elucidation of Its Molecular Mechanisms in High-Fat Diet-Fed C57BL/6 Mice.

Obesity is a threat to public health and effective new medications are required. Platycodonis Radix (PR) is a traditional medicinal/dietary plant with activities against obesity. Using mice given a diet rich in fat, the antiobesity components of PR were identified and their molecular mechanisms were clarified further in this investigation. Initially, the impacts of PR fractions on liver histology and biochemical markers were assessed. Subsequently, the degrees of lipogenic and lipolytic gene and protein expressions were determined. Oral administration of PR polysaccharides (PG) (0.80 g/kg body weight) improved liver function (alanine aminotransferase and aspartate aminotransferase) and its antioxidant activities (total superoxide dismutase, glutathione peroxidase, and malondialdehyde), as well as alleviated blood lipid (total cholesterol, total triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) values, inflammatory systemic (TNF-α and IL-1ß), and histological abnormalities within the liver. Furthermore, PG administration downregulated the expression for lipogenic genes (ACC and FAS) and upregulated the expression for the lipolytic gene (PPARα, LPL, CPT1, and HSL). Importantly, PG raised AMPK phosphorylation and decreased SREBP-1c protein synthesis. Thus, it is possible that PG stimulates the AMPK-LPL/HSL path (lipolytic route) plus the AMPK-ACC/PPARα-CPT1 path (associated to ß-oxidation of fatty acids), while inhibiting the AMPK/(SREBP-1c)-ACC/FAS path (lipogenic route). In summary, PG has the ability to regulate lipid metabolism, and it may be useful to pharmacologically activate AMPK with PG to prevent and cure obesity.

Effects of Extracellular Calcium Concentration on Hepatic Ischemia-Reperfusion Injury in a Rat Model.

OBJECTIVES: Hypocalcemia is frequently identified during liver transplant. However, supplementation of extracellular calcium could induce increased intracellular calcium concentration, as a potential factor for injury to the liver graft. We evaluated the effects of regulating extracellular calcium concentrations on hepatic ischemia-reperfusion injury. MATERIALS AND METHODS: We randomly divided 24 Sprague-Dawley rats into 3 groups: group C received normal saline (n = 8), group L received citrate to induce hypocalcemia (n = 8), and group L-Co received citrate followed by calcium gluconate to ameliorate hypocalcemia (n = 8). Liver enzyme levels and extracellular calcium were measured before surgery, 1 hour after ischemia, and 2 hours after reperfusion. The primary outcome was liver enzyme levels measured 2 hours after reperfusion. In addition, we evaluated intracellular calcium levels, lactate dehydrogenase activity, and histopathological results in liver tissue. RESULTS: Three groups demonstrated significant differences in extracellular calcium concentrations, but intracellular calcium concentrations in liver tissue were not significantly different. Group L showed significantly lower mean arterial pressure than other groups at 1 hour after ischemia (93.6 ± 20.8 vs 69.4 ± 14.2 vs 86.6 ± 10.4 mmHg; P = .02, for group C vs L vs L-Co, respectively). At 2 hours after reperfusion, group L showed significantly higher liver enzymes than other groups (aspartate aminotransferase 443.0 ± 353.2 vs 952.3 ± 94.8 vs 502.4 ± 327.3 U/L, P = .01; and alanine aminotransferase 407.9 ± 406.5 vs 860.6 ± 210.9 vs 333.9 ± 304.2 U/L, P = .02; for group C vs L vs L-Co, respectively). However, no significant difference was shown in lactate dehydrogenase and histological liver injury grade. CONCLUSIONS: Administering calcium to rats with hypocalcemia did not increase intracellular calcium accumulation but instead resulted in less hepatic injury compared with rats with low extracellular calcium concentrations in this rat model study.

Therapeutic Potential of Diosgenin in Amelioration of Carbon Tetrachloride-Induced Murine Liver Injury.

Diosgenin is a sapogenin with antidiabetic, antioxidant, and anti-inflammatory properties. The current study investigated whether diosgenin could ameliorate carbon tetrachloride (CCL4)-induced liver injury. To cause liver injury, CCL4 was injected intraperitoneally twice a week for 8 weeks. Daily oral administration of diosgenin at doses of 20, 40, and 80 mg/kg was started one day before CCL4 injection and continued for 8 weeks. Finally, serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and also albumin were assessed. Catalase and superoxide dismutase (SOD) activities in addition to glutathione (GSH) and malondialdehyde (MDA) levels were also quantified in the liver homogenate and routine histological evaluation was also conducted. Elevated serum levels of liver enzymes and decreased serum level of albumin caused by CCL4 were significantly restored following diosgenin administration at doses of 40 and 80 mg/kg. Long-term administration of CCL4 increased inflammatory and apoptotic factors such as IL-1ß, caspase 3, TNF-α, and IL-6 and decreased SOD and catalase activities as well as GSH level in liver homogenates; while MDA level was increased. Treatment with diosgenin increased SOD and catalase activities and GSH levels in the liver of injured animals. In addition, liver MDA, IL-1ß, caspase 3, TNF-α, and IL-6 level or activity decreased by diosgenin treatment. Additionally, diosgenin aptly prevented aberrant liver histological changes. According to obtained results, diosgenin can dose-dependently diminish CCl4-induced liver functional deficits and histological changes in a dose-dependent manner, possibly due to its antioxidant and anti-inflammation properties, and its beneficial effect is comparable to known hepatoprotective agent silymarin.

Effect of Pirdot Leaf Extract (Saurauia Vulcani Korth ) on SGPT and SGOT Value in Wistar Strain Rats Induced by Salmonella Typhimurium.

Background: Typhoid fever is an acute disease caused by Salmonella typhimurium that can invade the liver and cause symptoms of hepatomegaly,jaundice.Biochemically, these symptoms can be assessed by seeing the SGPT and SGOT levels increase. Pirdot Leaf is an herbal plant found in the Toba area of North Sumatra which has a lot of bioactive potential,namely flavonoids,steroids, saponins. Flavonoids are active substances that can overcome the inflammatory process, it is expected that the administration of Pirdot leaf extract can reduce levels of SGOT and SGPT in mice induced Salmonella Typhimurium. Objective: The purpose of this study was to determine the effect of ethanol extract of pirdot leaves on SGPT and SGOT values in rat models induced by Salmonella typhimurium. Methods: This study used 32 samples divided into four groups namely: Normal group, Negative group, Positive group and Treatment group. Results: The results were obtained for normal control SGPT (27,85) negative control (37,80) positive control (27,30) and for Dick treatment (26,21). The results of the study for SGPT obtained normal control (73,18), negative control (120,23), positive control (92,89), and treatment control (78,68). Conclusion: Giving ethanol extract of pirdot leaves effect on reducing SGPT and SGOT levels in wistar strain mice induced Salmonella typhimurium.

The hepatoprotective potentials of Olea europaea L. leaves against carbon tetrachloride-induced hepatic injury in rats.

OBJECTIVE: To examine the therapeutic effects of Olea europaea L. leaves extract on carbon tetrachloride-induced liver injury in rats. Methods: The experimental study was conducted at the Department of Physiology, University of Karachi, Karachi, in July 2021, and comprised Albino Wistar male rats weighing 180-220gm. The animals were divided into control group I, carbon tetrachloride group II, Olea europaea L. + carbon tetrachloride group III and Olea europaea L. group IV. In Vitro model of hepatic toxicity was developed by carbon tetrachloride. A daily dose of 50mg/kg of aqueous extract of olive leaves was administered orally and 0.8ml/kg of carbon tetrachloride was administered twice a week subcutaneously for 28 days. On the 29th day, the animals were sacrificed, and tested for hepatic enzymes, lipid peroxidation markers and histopathology. Data was analysed using SPSS 20. RESULTS: Of the 24 rats, 6(25%) were in each of the 4 groups. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin levels were significantly reduced (p<0.05) in group II whereas, 4- hydroxynonenal, isoprostane and malondialdehyde levels were significantly increased (p<0.05). However, total antioxidant level increased significantly (p<0.05) in group III compared to group II. Histopathology showed severe liver damage in group II and mild damage in group III. Conclusion: Olea europaea L. leaves extract was found to have profound hepatoprotective effects.

Protective Mechanisms of Juncus effusus and Carbonized Juncus effusus against D-Galactosamine-Induced Acute Liver Injury in Mice.

This study investigated the hepatoprotective effects of Juncus effusus (J. effusus) and Carbonized J. effusus against liver injury caused by D-galactosamine (D-GalN) in mice. J. effusus and Carbonized J. effusus were administered by gavage once daily starting seven days before the D-GalN treatment. The results of the study indicated that J. effusus and Carbonized J. effusus suppressed the D-GalN-induced generation of serum alanine transaminase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) was observed. The values of superoxide dismutase (SOD) exhibited an increase. In addition, J. effusus and Carbonized J. effusus promoted the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NADPH quinone oxidoreductase-1 (NQO-1), heme oxygenase-1 (HO-1) as well as the mRNA expression of Nrf2, HO-1, NQO-1 and Glutamate cysteine ligase catalytic subunit (GCLC). The compressed Carbonized J. effusus demonstrated the optimum impact. These results suggest that J. effusus and Carbonized J. effusus protect against D-GalN-induced acute liver injury through the activation of the Nrf2 pathway.

What is the influence of policosanol supplementation on liver enzymes? A systematic review and dose-response meta-analysis of randomized controlled trials.

OBJECTIVE: Policosanol is a mixture of long chain alcohols refined from sugar cane. Significant reductions in liver enzymes have been observed in some studies. However, the impact of policosanol on liver enzymes remained controversial. The current meta-analysis aims to evaluate the effect of policosanol supplementation on the levels of alanine transaminase (ALT) and aspartate transaminase (AST). METHODS: The literature was systematically searched for studies published up to November 2023 in PubMed/Medline, Google Scholar, EMBASE, and Scopus. Randomized controlled trial (RCT) studies were included to evaluate the intervention effect of policosanol compared to placebo on ALT and AST. DerSimonian and Laird models were used to calculate effect sizes. RESULTS: Twenty-three trials including 2535 participants were included in the study. The combination of effect sizes, regarding the random-effects model, demonstrated significant changes in ALT serum levels after intervention (WMD: -1.48 U/L; 95% CI: -2.33 to -0.64; P = 0.001), and AST (WMD: -1.10 U/L; 95% CI: -1.70 to -0.51; P < 0.001). Subgroup analysis of AST and ALT showed that this reduction effect was most often observed at the dose of 20 mg/d. The dose-response analysis represented a non-significant non-linear connection between the dosage and duration of policosanol intervention in ALT and AST serum reduction. CONCLUSION: Policosanol supplementation exerts a beneficial effect on liver enzymes as well as ALT and AST concentrations in adults. However, further long-term and well-designed RCTs with better quality are needed to further assess and confirm these results.

Citrus limon (L.) Osbeck Fruit Peel Extract Attenuates Carbon Tetrachloride-Induced Hepatocarcinogenesis in Sprague-Dawley Rats.

Background: Traditional herbal medicine practitioners in the Ashanti region of Ghana use the fruit peels of Citrus limon (L.) Osbeck (C. limon) in preventive and curative treatment of many cancers including liver cancer. This ethnobotanical claim remains to be verified scientifically. Aim of the Study. This study investigated prophylactic hepatoprotective and anti-HCC effects of C. limon peel extract (LPE) in CCl4/olive oil-induced HCC-like rats. Materials and Methods: After preparation of LPE, it was subjected to phytochemical screening using standard phytochemical methods. A total of 30 healthy adult male Sprague-Dawley rats (weighing 150-200 g) were randomly assigned into six groups of 5 rats each. Rats in the control group received olive oil (5 mL/kg ip) twice weekly for 16 weeks. Rats in the model group received CCl4/olive oil (2 mL/kg, ip) twice weekly for 16 weeks. Rats in capecitabine (10 mg/kg po) and LPE (50, 100, and 200 mg/kg po) groups received CCl4/olive oil (2 mL/kg, i.p) in the morning and their respective treatments in the afternoon twice a week for 16 weeks. Rats in all groups had free access to food and water ad libitum. Body weight and survival rates were monitored. Rats were sacrificed under deep anesthesia, blood was collected, and liver and other organs were isolated. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), prothrombin time, bilirubin, C-reactive protein (CRP), alpha- (α-) fetoprotein (AFP), and liver histology were assessed. Results: Alkaloids, tannins, flavonoids, terpenoids, and saponins were detected in LPE. Model rats demonstrated increased serum levels of AFP, CRP, ALP, GGT, ALT, and AST, prothrombin time, total bilirubin, direct bilirubin, blood lymphocyte, and monocyte counts, but decreased serum albumin and total protein compared to control rats. Unlike the control, model rats demonstrated fat accumulation in periportal and centrilobular hepatocytes and neoplastic transformation. Semiquantitation of periodic acid Schiff- (PAS-) stained liver sections showed decreased glycogen storage in hepatocytes of model rats compared to control rats. Compared to the model, LPE treatment protected against CCl4-induced hepatocarcinogenesis, which was evidenced by decreased AFP, CRP, liver enzymes, total and direct bilirubin, prothrombin time, and blood lymphocyte and monocyte counts; attenuation of fat accumulation; and increased glycogen storage, albumin, and total protein. Conclusion: LPE abates CCl4-induced hepatocarcinogenesis by attenuating liver inflammation and improving metabolic, biosynthetic, and detoxification functions of the liver. The prophylactic hepatoprotective and anti-hepatocarcinogenic effects of LPE are attributable to its phytochemical composition raising hopes of finding potential anticancer bioactive compounds from C. limon fruit peels.

Analyzing the Correlation Between Serum Biomarkers and Child-Pugh Score in Liver Cirrhosis.

Objective: This study aimed to analyze the diagnostic efficacy of serum biomarkers in liver cirrhosis patients categorized by Child-Pugh scores. Methods: An observational cross-sectional study design was employed. A total of 110 liver cirrhosis patients, classified according to Child-Pugh scores and 60 healthy individuals were included in this study. Serum levels of adenosine deaminase (ADA), adiponectin (APN), matrix metalloproteinase-2 (MMP-2), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured. Results: The levels of ADA, APN, MMP-2, ALP, ALT, and AST were significantly higher in the study group compared to the control group (P < .05). Furthermore, these levels increased with the severity of liver cirrhosis, with higher levels observed in patients with Child-Pugh class C. The positive diagnostic rates for joint detection in Child-Pugh class A, B, and C were 93.75% (30/32), 100% (34/34), and 100% (44/44), respectively. Conclusions: Combined detection of serum biomarkers improves the diagnostic efficacy of liver cirrhosis. The diagnostic rates were higher when considering Child-Pugh scores, with the highest rates observed in class C.

The effects of pomegranate consumption on liver function enzymes in adults: A systematic review and meta-analysis.

BACKGROUND: We performed a systematic review and meta-analysis of all published clinical trial studies to provide a more accurate estimation of pomegranate effects on liver enzymes in different clinical conditions. METHODS: A systematic literature search was carried out using electronic databases, including PubMed, Web of Science, and Scopus, up to March 2023 to identify eligible randomized clinical trials (RCTs) evaluating the effect of pomegranate consumption on liver function enzymes. Heterogeneity tests of the selected trials were performed using the I2 statistic. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as the weighted mean difference with a 95% confidence interval. RESULTS: Out of 3811 records, 9 eligible RCTs were included in the current study. However, there are limitations in the included studies, which can be mentioned in the dose, duration, and type of interventions that are different among the studies, as well as the small number of included studies. All this causes heterogeneity among studies and this heterogeneity limits the consistency of the results. Our meta-analysis showed that pomegranate intake had a significant effect on lowering aspartate aminotransferase (AST) levels in long-term intervention (> 8 weeks), obese (BMI≥30) individuals, or patients with metabolic disorders. Furthermore, results showed a significant decrease in alanine aminotransferase (ALT) levels in the long-term intervention (> 8 weeks) or in patients with metabolic disorders following the pomegranate intake. Combined results from the random-effects model indicated a significant reduction in gamma-glutamyl transferase (GGT) levels (WMD: -5.43 IU/L 95% CI: -7.78 to -3.08; p < 0.001;) following the pomegranate intake. The results of Egger's test mentioned a significant publication bias for the trials examining the effect of pomegranate intake on AST (p = 0.007) and ALT (p = 0.036). CONCLUSION: Our results suggest that long-term pomegranate intake may be effective in ameliorating liver enzymes in adults with obesity and metabolic disorders who are more likely to have elevated baseline liver enzymes due to some degree of liver injury or tissue damage. However, some studies failed to conduct independent biochemical characterization of the product used, including the presence and quantity of polyphenols, antioxidants, and proanthocyanidins.

Protective Effect of Hydroalcoholic Extract of Punica granatum Leaves on High Fructose Induced Insulin Resistance in Experimental Animals.

BACKGROUND: Insulin resistance (IR) is a condition characterized by reduced sensitivity of body tissues to insulin, leading to impaired regulation of downstream metabolic pathways and elevated blood glucose levels. Diets rich in fructose have been proven to cause insulin resistance in test rats, resulting in decreased insulin sensitivity, particularly in the liver, and compromised disposal of glucose from the body. In the search for effective treatments, Plant-derived formulations have gained popularity because to their ability for treating a variety of ailments. One such plant is Punica granatum Linn. from the Punicaceae family, which has long been used in the treatment of diabetes and its consequences. This study investigates the insulin-resistant activity of an extract from Punica granatum leaves. The study goal is to assess the possible protective role of Punica granatum against insulin resistance through various analyses, including serum glucose and insulin levels, lipid profile assessment, measurement of liver enzymes (ALP, SGOT, SGPT), and histopathological examination of liver sections. METHODS: The study involves several key methods to evaluate the insulin-resistant activity of Punica granatum extract in high fructose diet induced insulin resistance animal model. The extract was administered orally to the experimental animals. These methods include the measurement of serum glucose and serum insulin levels, analysis of the lipid profile, quantification of liver enzymes such as ALP, SGOT, and SGPT, and a detailed histopathological examination of liver tissue sections. These analyses collectively provide insights into the impact of Punica granatum extract on insulin resistance and related metabolic parameters. RESULTS: Findings of this study provide insight on the possible benefits of Punica granatum extract on insulin resistance. Through the assessment of serum glucose and insulin levels, lipid profile analysis, and measurement of liver enzymes, the study elucidates the impact of the extract on key metabolic indicators. Additionally, the histopathological examination of liver sections provides visual insights into the structural changes that may occur as a result of the treatment. CONCLUSION: In conclusion, this study highlights the ability of Punica granatum extract as a candidate for addressing insulin resistance. The findings suggest that the extract may have a protective role against insulin resistance, as evidenced by improvements in serum glucose and insulin levels, lipid profile, liver enzyme levels, and histopathological characteristics. Further research and investigations are warranted to fully understand the mechanisms underlying these observed effects and to validate the potential of Punica granatum extract as a therapeutic option for managing insulin resistance and its associated complications.

Effect of Ethanol Extract of Soursop (Annona muricata L.) Stem Bark on Rat Liver Function.

<b>Background and Objective:</b> Paracetamol does not cause toxic effects if given in therapeutic doses, namely below 4 g per day. Use of paracetamol at a dose of more than 4 g per day can result in hepatotoxicity. This study aims to compare the hepatoprotector potency of the ethanol extract of soursop stem bark (<i>A. muricata</i>) against the enzyme activity of SGOT and SGPT in rats induced by toxic doses of paracetamol. <b>Materials and Methods:</b> A Completely Randomized Design (CRD) comprised of 6 treatment groups and 3 replications. Total 27 white male rats were induced hepatotoxicity with 1350 mg of paracetamol on the 7th day, except for normal control (K0) which was given aquadest. The tested animals received akuades as the negative control (K-) 11.34 mg kg¹ b.wt., of Hepa-Q as the positive control (K+), ethanol extract stem bark <i>Annona muricata</i> at a dose of 150 mg kg¹ BB (P1), 300 mg kg¹ BB (P2) and 600 mg kg¹ BB (P3). <b>Results:</b> There was a significant difference (p<0.05) in the levels of SGOT and SGPT after giving ethanol extract of soursop (<i>A. muricata</i>) stem bark. The best treatment for reducing SGOT and SGPT levels in rats induced by paracetamol was the administration of ethanol extract of <i>A. muricata</i> stem bark at a dose of 600 mg kg¹ BB. <b>Conclusion:</b> Based on the results of the study, it was concluded that all ethanol extract of <i>Annona muricata</i> L. stem bark (EEAMSB) doses had the potential to reduce the levels of AST and ALT in paracetamol-induced rats.

Effect of dietary onion (Allium cepa L.) powder as an antioxidant on semen quality, blood biochemicals, and reproductive parameters, as well as immunological variables of rabbit bucks under severe heat stress.

This study aimed to evaluate the antioxidant effects of onion (Allium cepa L.) powder on the immunological variables, redox state, and semen quality of rabbit bucks exposed to severe heat stress. Thirty-six mature bucks (7 months old) were divided into three groups consisting of 12 bucks each, namely group I, control; group II, 400 mg onion powder/kg diet; and group III, 800 mg onion powder/kg diet. The quality of semen was evaluated for volume, pH, motility, concentration, total sperm output, viability, and packed sperm volume. Blood samples were collected in the 12th week for estimation of red blood cells (RBC), white blood cells (WBC), and erythrocytic indices. Serum proteins, glutamate oxaloacetate (GOT), glutamate pyruvate transaminase (GPT), urea, creatinine, testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), immunoglobulins, malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione, superoxide dismutase (SOD), and catalase (CAT) were measured. The temperature-humidity index (THI) obtained was within the range of 28.85-33.08 indicating severe heat stress. The results show that mass and individual motility, concentration, total sperm output, sperm viability, and packed sperm volume were higher (P < 0.05) in groups II and group III, with group III having the highest (P < 0.05) levels compared to group I. Compared to group I, groups II and III had higher (P < 0.05) concentrations of RBC, MCV, MCH, FSH, LH, SOD, and catalase. The highest concentration (P < 0.05) of GPT was obtained in group III compared to other groups. The highest concentration of IgG (P < 0.05) was obtained in group II while the lowest was in group I. In conclusion, dietary supplementation with onion powder at 400 or 800 mg/kg diet improves semen quality, RBC, FSH, LH, SOD, catalase, and IgG while ameliorating the adverse effects of heat stress and improve the health and reproduction of rabbits.

Mendelian randomization to evaluate the causal relationship between liver enzymes and the risk of six specific bone and joint-related diseases.

Background: Studies of liver dysfunction in relation to bone and joint-related diseases are scarce, and its causality remains unclear. Our objective was to investigate whether serum liver enzymes are causally associated with bone and joint-related diseases using Mendelian randomization (MR) designs. Methods: Genetic data on serum liver enzymes (alkaline phosphatase (ALP); alanine transaminase (ALT); gamma-glutamyl transferase (GGT)) and six common bone and joint-related diseases (rheumatoid arthritis (RA), osteoporosis, osteoarthritis (OA), ankylosing spondylitis, psoriatic arthritis, and gout) were derived from independent genome-wide association studies of European ancestry. The inverse variance-weighted (IVW) method was applied for the main causal estimate. Complementary sensitivity analyses and reverse causal analyses were utilized to confirm the robustness of the results. Results: Using the IVW method, the positive causality between ALP and the risk of osteoporosis diagnosed by bone mineral density (BMD) at different sites was indicated (femoral neck, lumbar spine, and total body BMD, odds ratio (OR) [95% CI], 0.40 [0.23-0.69], 0.35 [0.19-0.67], and 0.33 [0.22-0.51], respectively). ALP was also linked to a higher risk of RA (OR [95% CI], 6.26 [1.69-23.51]). Evidence of potential harmful effects of higher levels of ALT on the risk of hip and knee OA was acquired (OR [95% CI], 2.48 [1.39-4.41] and 3.07 [1.49-6.30], respectively). No causal relationship was observed between GGT and these bone and joint-related diseases. The study also found that BMD were all negatively linked to ALP levels (OR [95% CI] for TBMD, FN-BMD, and LS-BMD: 0.993 [0.991-0.995], 0.993 [0.988-0.998], and 0.993 [0.989, 0.998], respectively) in the reverse causal analysis. The results were replicated via sensitivity analysis in the validation process. Conclusions: Our study revealed a significant association between liver function and bone and joint-related diseases.

The Effect of Vitamin E Supplementation on Serum Aminotransferases in Non-Alcoholic Fatty Liver Disease (NAFLD): A Systematic Review and Meta-Analysis.

Νon-alcoholic fatty liver disease (NAFLD) is a common cause of end-stage liver disease in developed countries. Oxidative stress plays a key role during the course of the disease and vitamin E supplementation has shown to be beneficial due to its antioxidative properties. We aim to investigate the effect of vitamin E supplementation on serum aminotransferase levels in patients with NAFLD. Three electronic databases (MEDLINE, CENTRAL, and Embase) were reviewed for randomized trials that tested vitamin E supplementation versus placebo or no intervention in patients with NAFLD, published until April 2023. A total of 794 patients from 12 randomized trials were included in this meta-analysis. Notwithstanding the studies' heterogeneity and moderate internal validity in certain cases, among studies testing vitamin E supplementation at 400 IU/day and above, the values of alanine aminotransferase (ALT) were reduced compared with placebo or no intervention [ALT Mean Difference (MD) = -6.99 IU/L, 95% CI (-9.63, -4.35), for studies conducted in Asian countries and MD = -9.57 IU/L, 95% CI (-12.20, -6.95) in non-Asian countries]. Regarding aspartate aminotransferase (AST), patients in the experimental group experienced a reduction in serum levels, though smaller in absolute values [AST MD = -4.65 IU/L, 95% CI (-7.44, -1.86) in studies conducted in Asian populations] and of lower precision in non-Asian studies [MD = -5.60 IU/L, 95% CI (-11.48, 0.28)].

Change to Mixed-Lipid Emulsion From Soybean Oil-Based Lipid Emulsion in Pediatric Patients.

Importance: Critically ill pediatric patients often require parenteral nutrition (PN) in the intensive care unit (ICU). Literature suggests mixed lipid emulsions (LE) with soybean oil reduction strategies may improve outcomes. Objective: To examine the association of a hospital-wide switch to a mixed-lipid formula (4-OLE) with pediatric outcomes. Design, Setting, and Participants: Retrospective cohort study at a large US academic referral center. Pediatric patients aged 1 month to 17 years requiring parenteral nutrition from May 2016 to September 2019 were included. Data were analyzed from October 2020 to February 2023. Exposure: In 2017, Duke University Health System fully converted to a soybean oil/MCT/olive/fish oil lipid (4-OLE) from pure soybean oil-based LE in pediatric patients. Pediatric patients before the change (Intralipid [IL] group) were compared with patients after (4-OLE group). Main Outcomes and Measures: Clinical outcomes were compared between treatment periods via multivariable regression models. The primary outcome was hospital length of stay (LOS). Fourteen secondary outcomes included hospital mortality of any cause, 30-day or 90-day readmission, pneumonia, urinary tract infections (UTIs), total caloric delivery, and liver function tests (aspartate aminotransferase, alanine transaminase, alkaline phosphatase, and total bilirubin). Results: A total of 684 children dependent on PN were identified (342 were critically ill), with 30% (206 children) in the preswitch (IL) period and 70% (478 children) in the postswitch (4-OLE) period; 123 were male (59.7%). In comparing IL vs 4-OLE, there was a significant difference in median (IQR) age (4.0 [1.2-13.0] vs 3.0 [0.8-9.0] years, respectively; P = .04), without difference in body mass index or baseline comorbidities except for significant differences in cancer diagnosis (26 patients in the IL group [12.6%] vs 29 patients in the 4-OLE group [6.1%]; P = .004) and chronic obstructive pulmonary disease (24 patients in the IL group [11.7%] vs 30 patients in the 4-OLE group [6.3%]; P = .02). In the all children cohort, 4-OLE was associated with shorter hospital LOS (IRR, 0.81; 95% CI, 0.05-0.78), and reduced UTI risk (OR, 0.33; 95% CI, 0.18-0.64). In the ICU cohort, 4-OLE was associated with shorter hospital LOS (IRR, 0.81; 95% CI, 0.78-0.83), and reduced UTI risk (OR, 0.23; 95% CI, 0.11-0.51). Other secondary outcomes were not significant. Conclusions and Relevance: In this observational study of clinical outcomes among children dependent on PN, a switch to 4-OLE in a large academic hospital was associated with a significant decrease in hospital LOS in ICU and non-ICU patients. These findings suggest switching to a soy-LE sparing strategy using 4-OLE is feasible, safe, and associated with improved clinical outcomes in pediatric PN patients.

An in vivo and in silico evaluation of the hepatoprotective potential of Gynura procumbens: A promising agent for combating hepatotoxicity.

INTRODUCTION: The liver, the most important metabolic organ of the body, performs a wide variety of vital functions. Hepatic cell injury occurs by the activation of reactive oxygen species (ROS) that are generated by carbon tetrachloride (CCl4), xenobiotics, and other toxic substances through cytochrome P450-dependent steps resulting from the covalent bond formation with lipoproteins and nucleic acids. Observing the urgent state of hepatotoxic patients worldwide, different medicinal plants and their properties can be explored to combat such free radical damage to the liver. In vivo and in silico studies were designed and conducted to evaluate the antioxidant and hepatoprotective properties of Gynura procumbens in rats. MATERIALS AND METHODS: Gynura procumbens leaves were collected and extracted using 70% ethanol. The required chemicals CCl4, standard drug (silymarin), and blood serum analysis kits were stocked. The in vivo tests were performed in 140 healthy Wister albino rats of either sex under well-controlled parameters divided into 14 groups, strictly maintaining Institutional Animal Ethics Committee (IEAC) protocols. For the histopathology study, 10% buffered neutral formalin was used for organ preservation. Later the specimens were studied under a fluorescence microscope. In silico molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies were performed, and the results were analyzed statistically. RESULTS AND DISCUSSION: Gynura procumbens partially negate the deleterious effect of carbon tetrachloride on normal weight gain in rats. The elevated level of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), creatinine, LDH, total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG), malondialdehyde (MDA), deoxyribonucleic acid (DNA) fragmentation ranges, gamma-glutamyl transferase (γ-GT) in CCl4 treated groups were decreased by both standard drug silymarin and G. procumbens leaf extract. We have found significant & highly significant changes statistically for different doses, here p<0.05 & p<0.01, respectively. On the other hand, G. procumbens and silymarin displayed Statistically significant (p<0.05) and high significant(p<0.01) increased levels of HDL, CAT SOD (here p<0.05 & p<0.01 for different doses) when the treatment groups were compared with the disease control group. Because the therapeutic activity imparted by plants and drugs accelerates the movement of the disturbed pathophysiological state toward the healthy state. In the molecular docking analysis, G. procumbens phytoconstituents performed poorly against transforming growth factor-beta 1 (TGF-ß1) compared to the control drug silymarin. In contrast, 26 phytoconstituents scored better than the control bezafibrate against peroxisome proliferator-activated receptor alpha (PPAR-α). The top scoring compounds for both macromolecules were observed to form stable complexes in the molecular dynamics simulations. Flavonoids and phenolic compounds performed better than other constituents in providing hepatoprotective activity. It can, thus, be inferred that the extract of G. procumbens showed good hepatoprotective properties in rats.

[Interventional effect and mechanism of fermentation liquid of Dendrobium officinale leaves on alcoholic hepatitis mice].

Objective: To explore the intervention effect and mechanism of Dendrobium officinale leaf fermentation liquid on alcoholic hepatitis (AH) mice. Methods: Seventy inbred C57BL/6J male mice aged 6-8 weeks were selected and randomly divided into normal group (NG), model group (MG), liquid feed control group (CG), silybum group (SI), low-dose group (DL), medium-dose group (DM), and high-dose group (DH) of Dendrobium officinale fermentation liquid, with 10 mice in each group. NG group was given common feed, CG group was given control feed (LB alcoholic liquid control feed), SI group was given LB alcoholic liquid feed and silybum by gavage, DL, DM and DH groups were given LB alcoholic liquid feed and 25%, 50% and 100% concentration of Dendrobium officinale leaf fermentation liquid by gavage. An AH model was established by feeding LB alcoholic liquid feed for 8 weeks.At week 8, alanine Transaminase (ALT), triglyceride (TG), transferrin (TRF), interleukin (IL)-6, IL-10, and IL-1ß, tumor necrosis factor-α(TNF-α), interferon-γ(IFN-γ) were detected in eye blood of mice. Liver tissues were stained with HE, Oil Red O, Prussian blue and immunofluorescence ROS. The contents of glutathione(GSH) and malondialdehyde (MDA) in liver tissue homogenate were detected. To analyze the intervention effect and mechanism of Dendrobium officinale leaf fermentation solution on AH mice, the mRNA and protein relative expression levels of adenylate activated protein kinase (AMPK), AMPKß1, phosphorylated AMPKß1 (p-AMPKß1), tumor suppressor gene p53 (p53), solsolic vector family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GXP4) were detected by polymerase chain reaction (PCR) and Western blot. Results: Compared with MG group, the serum ALT and TG levels in the DL, DM, and DH groups were all reduced [ALT: (45.94±19.85), (45.73±22.62), and (41.68±7.13) vs (75.51±17.76) U/L, respectively; TG: (0.90±0.23), (0.69±0.22) and (0.41±0.20) vs (1.28±0.19) mmol/L, respectively, all P<0.05]; IL-6, IL-1ß, TNF-α, IFN-γ were decreased (all P<0.05). The serum TRF and IL-10 levels in the DM and DH groups were increased (all P<0.05). Compared with MG group, the liver tissue MDA of mice in DL, DM and DH groups was decreased [(0.41±0.05), (0.40±0.03), and (0.43±0.14) vs (0.64±0.06)µmol/g, respectively], GSH was increased (all P<0.05). Compared with MG, mRNA expression levels of AMPK (1.36±0.11, 1.61±0.17, 1.68±0.11 vs 0.80±0.12, respectively), SLC7A11 (0.91±0.12, 0.97±0.12, 0.99±0.13 vs 0.60±0.14, respectively) and GPX4 (0.51±0.11, 0.63±0.17, 0.83±0.15 vs 0.42±0.14, respectively) in the liver tissue of DL, DM and DH groups were all increased (all P<0.05). Compared with MG group, DL, DM and DH groups showed the relative expression levels of AMPKß1, p-AMPKß1, SLC7A11 and GPX4 were increased in the liver tissue of mice, while the relative expression levels of p53 protein were decreased (all P<0.05). Compared with MG group, DL, DM and DH groups reduced the degree of hepatic steatosis and inflammation in the lobules, while the iron and ROS staining in the liver tissue became lighter. Conclusion: Dendrobium officinale leaf fermentation liquid can alleviate the severity of AH in mice, and its mechanism may be related to the up-regulation of AMPK to inhibiting the p53/SLC7A11/GPX4 mediated Ferroptosis pathway.

Scopoletin a potential phytochemical therapy for antitubercular treatment drug induced liver injury (ATT-DILI) model in Wistar rats.

OBJECTIVES: The hepatoprotective properties of scopoletin have been explored in carbon tetrachloride (CCl4) induced liver injury but not in drug-induced liver injury (DILI) scenarios. Only N-acetyl-cysteine (NAC) has proven efficacy in DILI treatment. Accordingly, we conducted a study to assess the hepatoprotective action of scopoletin in the anti-tubercular treatment (ATT)-DILI model in Wistar rats, if any. METHODS: A total of 36 rats were evaluated, with six in each group. A 36-day ATT at 100 mg/kg dose for isoniazid, 300 mg/kg for rifampicin and 700 mg/kg for pyrazinamide were fed to induce hepatotoxicity in rats. Group I and II-VI received normal saline and ATT, respectively. Oral scopoletin (1,5 and 10 mg/kg) and NAC 150 mg/kg were administered in groups III, IV, V and VI, respectively, once daily for the last 15 days of the experiment. LFT monitoring was performed at baseline, days 21, 28, and 36. Rats were sacrificed for the histopathology examination. RESULTS: Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin levels were significantly increased in group II (receiving ATT) compared to normal control on day 28 and day 36 (p<0.05). All three doses of scopoletin and NAC groups led to the resolution of AST, ALT, ALP, and bilirubin changes induced by ATT medications effect beginning by day 28 and persisting on day 36 (p<0.01). An insignificant effect was observed on albumin and total protein levels. The effect was confirmed with antioxidants and histopathology analysis. CONCLUSIONS: The study confirms the hepatoprotective efficacy of scopoletin in a more robust commonly encountered liver injury etiology.