Alanine Aminotransaminase Levels Research Articles

Clinical effectiveness of combined Bifidobacterium live bacteria preparation and entecavir therapy in the management of Hepatitis B cirrhosis

Purpose: To investigate the efficacy of combining Bifidobacterium live bacteria preparation with entecavir in the treatment of hepatitis B cirrhosis and its effect on cytokines and liver function. 
 Methods: 88 patients with HBV-induced cirrhosis admitted to Qinzhou People’s Hospital, Qinzhou, China between January 2021 and January 2023 were divided into control and study groups with 44 patients each. Control group received entecavir, while study group received Bifidobacterium live bacteria preparation in addition to entecavir. Clinical treatment outcomes, liver function, liver fibrosis, immune function, and inflammatory cytokine indices were compared between the two groups. 
 Results: There was a significant increase in total effective rate of treatment in study group (95.45 %) compared to control group (79.55 %; p < 0.05). After treatment, the study group showed significantly lower levels of alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), total bilirubin (TBIL), hyaluronic acid (HA), laminin (LN), N-terminal propeptide of type III procollagen (PIIINP), and type IV collagen (IV-C), and higher levels of CD4+ and CD4+/CD8+ compared to control group (p < 0.05). Furthermore, study group exhibited significantly lower levels of IL-6, TNF-α, and HS-CRP after treatment compared to control group (p < 0.05). 
 Conclusion: The combined use of Bifidobacterium live bacteria preparation and entecavir in treating HBV-induced cirrhosis demonstrates significant clinical improvement. This combined approach effectively enhances liver function, improves immune response reduces inflammation and liver fibrosis. Hence, in future studies, efforts will be directed towards improving absorption and reducing the metabolism/excretion of the drug to validate these findings.

Perioperative Changes in Serum Transaminase Levels: Impact on Postoperative Morbidity Following Liver Resection of Hepatocellular Carcinoma.

To define how dynamic changes in pre- versus post-operative serum aspartate aminotransferase (AST) and alanine aminotransaminase (ALT) levels may impact postoperative morbidity after curative-intent resection of hepatocellular carcinoma (HCC). Hepatic ischemia/reperfusion can occur at the time of liver resection and may be associated with adverse outcomes following liver resection. Patients who underwent curative resection for HCC between 2010-2020 were identified from an international multi-institutional database. Changes in AST and ALT (CAA) on postoperative day (POD) 3 versus preoperative values () were calculated using the formula: based on a fusion index via Euclidean norm, which was examined relative to the comprehensive complication index (CCI). The impact of CAA on CCI was assessed by the restricted cubic spline regression and Random Forest analyses. A total of 759 patients were included in the analytic cohort. Median CAA was 1.7 (range, 0.9 to 3.25); 431 (56.8%) patients had a CAA<2, 215 (28.3%) patients with CAA 2-5, and 113 (14.9%) patients had CAA ≥5. The incidence of post-operative complications was 65.0% (n=493) with a median CCI of 20.9 (IQR, 20.9-33.5). Spline regression analysis demonstrated a non-linear incremental association between CAA and CCI. The optimal cutoff value of CAA=5 was identified by the recursive partitioning technique. After adjusting for other competing risk factors, CAA≥5 remained strongly associated with risk of post-operative complications (Ref. CAA<5, OR 1.63, 95%CI 1.05-2.55, P=0.03). In fact, the use of CAA to predict post-operative complications was very good in both the derivative (AUC 0.88) and external (ACU 0.86) cohorts (n=1137). CAA was an independent predictor of CCI after liver resection for HCC. Use of routine labs such as AST and ALT can help identify patients at highest risk of post-operative complications following HCC resection.

RNF115/BCA2 deficiency alleviated acute liver injury in mice by promoting autophagy and inhibiting inflammatory response

The E3 ubiquitin ligase RING finger protein 115 (RNF115), also known as breast cancer-associated gene 2 (BCA2), has been linked with the growth of some cancers and immune regulation, which is negatively correlated with prognosis. Here, it is demonstrated that the RNF115 deletion can protect mice from acute liver injury (ALI) induced by the treatment of lipopolysaccharide (LPS)/D-galactosamine (D-GalN), as evidenced by decreased levels of alanine aminotransaminase, aspartate transaminase, inflammatory cytokines (e.g., tumor necrosis factor α and interleukin-6), chemokines (e.g., MCP1/CCL2) and inflammatory cell (e.g., monocytes and neutrophils) infiltration. Moreover, it was found that the autophagy activity in Rnf115−/− livers was increased, which resulted in the removal of damaged mitochondria and hepatocyte apoptosis. However, the administration of adeno-associated virus Rnf115 or autophagy inhibitor 3-MA impaired autophagy and aggravated liver injury in Rnf115−/− mice with ALI. Further experiments proved that RNF115 interacts with LC3B, downregulates LC3B protein levels and cell autophagy. Additionally, Rnf115 deletion inhibited M1 type macrophage activation via NF-κB and Jnk signaling pathways. Elimination of macrophages narrowed the difference in liver damage between Rnf115+/+ and Rnf115−/− mice, indicating that macrophages were linked in the ALI induced by LPS/D-GalN. Collectively, for the first time, we have proved that Rnf115 inactivation ameliorated LPS/D-GalN-induced ALI in mice by promoting autophagy and attenuating inflammatory responses. This study provides new evidence for the involvement of autophagy mechanisms in the protection against acute liver injury.

Development and Validation of a Nomogram to Predict Significant Liver Inflammation in Patients with Chronic Hepatitis B.

Noninvasive diagnosis of liver inflammation is important for patients with chronic hepatitis B (CHB). This study aimed to develop a nomogram to predict significant liver inflammation for CHB patients. CHB patients who underwent liver biopsy were retrospectively collected and randomly divided into a development set and a validation set. The least absolute shrinkage and selection operator regression and logistic regression analysis were used to select independent predictors of significant liver inflammation, and a nomogram was developed. The performance of nomogram was assessed by receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). A total of 1019 CHB patients with a median age of 39.0 years were included. Alanine aminotransaminase (ALT, P = 0.018), gamma-glutamyl transpeptidase (P = 0.013), prothrombin time (P < 0.001), and HBV DNA level (P = 0.030) were identified as independent predictors of significant liver inflammation in the development set. A model namely AGPD-nomogram was developed based on the above parameters. The area under the ROC curve in predicting significant inflammation was 0.765 (95% CI: 0.727-0.803) and 0.766 (95% CI: 0.711-0.821) in the development and validation sets, which were significantly higher than other indexes. The AGPD-nomogram had a high predictive value in patients with normal ALT. Moreover, the nomogram was proven to be clinically useful by DCA. A visualized AGPD-nomogram which incorporated routine clinical parameters was proposed to facilitate the prediction of significant liver inflammation in CHB patients. This nomogram had high accuracy in the identification of significant liver inflammation and would be a useful tool for the better management of CHB patients, especially for those with normal ALT.

Application of Molecularly Imprinted Microelectrode as a Promising Point-of-Care Biosensor for Alanine Aminotransferase Enzyme

Alanine amino transaminase (ALT) is an enzyme that can be used as a biomarker for liver injury and other diseases. In this work, we report the development of the first microelectrode based on a molecularly imprinted pyruvate oxidase enzyme to be applied as an electrochemical biosensor for ALT detection. The biosensor is based on pyruvate oxidase enzyme (POx), imprinted using 4-aminophenol (functional monomer-on-platinum microelectrode modified (PME)) with platinum nanoparticles and 4-aminoantypirine (4-AAP)/sodium pyruvate as an electrochemical indicator. The operational conditions of the biosensor were optimized and characterized morphologically using scanning electron microscopy (SEM) and electrochemically using electrochemical impedance spectroscopy (EIS). The biosensor was found to have a fast response towards ALT within a linear range of 25–700 U/L and a limit of detection of 2.97 U/L. The biosensor did not exhibit cross-reactivity towards other tested enzymes, including nicotinamide adenine dinucleotide (Beta-NAD), catalase (CAT), glutathione peroxidase (GPx), and L-glutathione reduced (GSH) enzymes. The biosensor was efficiently applied for the assay of ALT in plasma samples; with recovery values ranging from 99.80–103.82% and RSD of values 0.27–2.01% and these results were found to be comparable to those of the reference diagnostic kits, without any need for complicated procedures or protein extraction. In addition to being highly sensitive, low cost, and portable, the use of microelectrodes allows the application of the proposed sensor for point-of-care diagnostics of liver function and online monitoring of ALT levels in hospitalized patients without the need for withdrawing samples, which indicates the promising applicability of the presented ALT sensor for point-of-care diagnostics.

Elevated Hepatic Steatosis Index is Associated with the Development of Adverse Maternal, but Not Adverse Neonatal, Outcomes: A Retrospective Cohort Study.

To determine whether an elevated hepatic steatosis index (HSI), a non-invasive test for possible metabolic dysfunction-associated fatty liver disease (MAFLD), is associated with the development of adverse pregnancy outcomes. A retrospective cohort study was conducted on adult women with singleton pregnancies who delivered at two tertiary hospitals from August 2014 to December 2017. Aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) levels obtained 12 months pre-gravid, or during pregnancy but prior to screening for gestational diabetes mellitus (GDM), were extracted and linked with oral glucose tolerance test results. The HSI was calculated using the following equation: 8 × (ALT/AST ratio) + BMI (+2 if female; +2 if diabetes mellitus present) and considered elevated if >36. Multiple logistic regression analysis was used to quantify the association between elevated HSI and each composite adverse pregnancy outcome after adjusting for independent maternal risk factors. Over 40-months, 11929 women were eligible and of these, 1885 had liver enzymes collected. Women with an elevated HSI (>36) were more likely multiparous and overweight/obese compared to those women with a non-elevated HSI (≤36). Elevated HSI was significantly associated with a composite of adverse maternal outcomes (adjusted odds ratio (aOR) 1.55 95% CI 1.11-2.17, p=0.01), although a non-significant increased risk of a composite of adverse neonatal outcomes occurred after multivariable adjustment (aOR 1.17, 95% CI 0.94-1.45, p=0.17). Over and above known maternal risk factors, women with elevated HSI were more likely to develop adverse maternal, but not adverse neonatal outcomes.

Effect of Nutmeg on Transaminase Activities in Liver and Serum of Adult Wistar rats

This study examines the activities of alanine aminotransaminase (ALT) and aspartate aminotransferase (AST) in the liver of 30 adult Wistar rats exposed to nutmeg for 30 days. 1 g of nutmeg was administered to group A (n=10), 2 g of nutmeg to group B (n=10) and group C (n=10) was used as the control. Enzyme activities were assayed in both serum and liver (tissue homogenate) spectrophotometrically. Results obtained showed a significant increase (p &lt; 0.05) in level of AST in serum of rats in group A and B (20.2±7.29 and 23.2 ± 3.27 U/L) when compared to the control group (14.8± 1.78 U/L) while serum ALT level was significantly reduced (5.2± 1.78 and 4.2 ± 0.04 U/L) compared to the control group (7.0 ± 2.6 U/L) but the differences based on dosage was statistically insignificant (p≥ 0.05). The enzyme activities in liver tissue homogenate showed a significant increase (p˂ 0.05) in AST levels (13.8 ± 1.14, 14.6 ± 1.78 and 12.8 ± 0.08 U/L) among test groups and between controls but ALT levels though lower in treated groups than control, was statistically insignificant (p≥ 0.05) among test and between control group (4.6 ± 1.34, 4.0 ± 0.08 and 5.8 ± 0.03 U/L). Differences in enzyme activities due to nutmeg administration may lead to hepatocellular injury as well as myocardial infarction. The results suggests that dosage and long-term consumption of nutmeg could have severe health implication as it affects liver function as well as other associated organ of the body.

Favipiravir-induced inflammatory and hydropic degenerative liver injury in rats.

Favipiravir is very effective in the treatment of many viral infections, especially at high doses. It was used at such doses to treat coronavirus disease 2019 (COVID-19) during the pandemic. However, liver damage was reported in patients undergoing such treatment. This study aimed to investigate the effects of low and high doses of favipiravir on the liver of rats, using biochemical and histopathological methods. Wistar albino rats were allocated to one of 3 groups, namely a healthy group (HG), a 100 mg/kg favipiravir (FAV-100) group and a 400 mg/kg favipiravir (FAV-400) group. Favipiravir was administered orally at 100 mg/kg and 400 mg/kg doses to the FAV-100 (n = 6) and FAV-400 (n = 6) groups, respectively. Distilled water was administered orally (1 mL) using the same method to the HG (n = 6). This procedure was repeated twice a day for 1 week. At the end of this period, the animals were euthanized with a high dose of thiopental anesthesia (50 mg/kg) and their liver tissues were removed. Favipiravir caused an increase in malondialdehyde (MDA), nuclear factor kappa B (NF-κB) and interleukin 6 (IL-6) levels in the liver tissue, as well as elevated alanine aminotransaminase (ALT) and aspartate aminotransferase (AST) levels in the blood. Moreover, favipiravir caused a decrease in total glutathione (tGSH), superoxide dismutase (SOD) and catalase (CAT) levels. In addition, severe edema, lymphocyte infiltration and hydropic degeneration were observed in the liver tissue of the FAV-400. High-dose favipiravir caused more significant oxidative and inflammatory damage in the liver tissue of rats than low-dose favipiravir.

The efficacy and tolerability of glecaprevir/pibrentasvir treatment in a real-world chronic hepatitis C patients cohort.

The aims of the present study were to evaluate the real-life efficacy and tolerability of glecaprevir (GLE)/pibrentasvir (PIB) in the treatment of patients with chronic hepatitis C (CHC). Between May 2019 and May 2022, 686 patients with CHC, treated with GLE/PIB combination from 21 participating centers in Turkiye, were enrolled in the study. All patients were Caucasian, and their median age was 56 years. At the start of GLE/PIB treatment, the median serum Hepatitis C virus RNA and serum alanine amino transaminase (ALT) levels were 6.74 log10 IU/mL and 47 U/L, respectively. Fifty-three percent of the patients were infected with genotype 1b, followed by genotype 3 (17%). Diabetes was the more common concomitant disease. The sustained virological response (SVR12) was 91.4% with intent-to-treat analysis and 98.5% with per protocol analysis. The SVR12 rates were statistically significant differences between the patients who were i.v. drug users and non-user (88.0% vs. 98.8%, p=0.025). From the baseline to SVR12, the serum ALT levels and Model for End-Stage Liver Disease score were significantly improved (p<0.001 and p=0.014, respectively). No severe adverse effect was observed. GLE/PIB is an effective and tolerable treatment in patients with CHC.

Risk Factors Associated With a Large Vertical Cup-to-Disc Ratio: Korean National Health and Nutritional Examination Survey.

Higher intraocular pressure, higher systolic blood pressure, and higher serum aspartate transaminase to alanine aminotransaminase level were risk factors associated with a large vertical cup-to-disk ratio (vCDR). To identify risk factors for a large vCDR using data from the Korea National Health and Nutritional Examination Survey (2008-2012). Out of the total 29,322 participants aged 20 or older who participated in Korea National Health and Nutrition Survey (KHANES) from the year 2008 to 2012, this study was conducted on 21,780 participants, excluding 1449 of them without fundus photographs and 6093 of them with missing values. To identify the risk factors associated with a large vCDR, the participants were divided into 2 groups: ≥0.6 and <0.6. Of the 21,780 subjects, 2357 of them had a vCDR ≥0.6 and 19,423 had a vCDR <0.6. There were significant differences in age, sex, and educational levels between the 2 groups. After adjusting age, sex, education level, and survey year by propensity score matching, in the group having vCDR ≥0.6, intraocular pressure (IOP) was high, systolic blood pressure (SBP) was high, and serum aspartate transaminase to alanine aminotransaminase level (AST/ALT ratio) was high ( P <0.001, P <0.001, and P <0.001). The results of multiple logistic regression analyses revealed that high IOP, high SBP, high myopia, and high AST/ALT ratio were risk factors for vCDR ≥0.6 ( P <0.001, P =0.006, P =0.005, P <0.001). In this study, risk factors associated with large vCDR were analyzed. Higher IOP, higher SBP, and higher AST/ALT ratio were related to vCDR ≥0.6.

Effects of the Antiobesity Drugs Aplex and Venera on Certain Biochemical and Physiological Indices in Obese Adult Male Albino Rats.

Background Because of the growing incidence of obesity, the use of synthetic antiobesity medicines as weight-loss agents has grown in popularity, although their usefulness has yet to be established. Two of such medicines are Aplex and Venera. This study is designed to determine the potential dangers of Aplex and Venera on certain biochemical and physiological indicators in obese adult male rats. Methods Twenty-one obese male albino rats (9 weeks old and having a body mass of 220 ± 20 g) were divided into three equal groups: the control group (vehicle treatment), the Aplex group (0.1 mg/kg/day) for 30 days, and the Venera group (0.1 mg/kg/day) for 30 days. Results The values of serum glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), total protein, total cholesterol (TC), high-density lipoprotein (HDL), very-low-density lipoprotein (VLDL), TC/HDL ratio, testosterone, thyroxine (T4), and leptin did not differ significantly between the treated and control groups. In contrast, the treated groups had substantial changes in bodyweight, serum alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), albumin, globulin, albumin/globulin ratio (A/G ratio), triglycerides (TG), low-density lipoproteins (LDL), LDL/HDL ratio, urea, creatinine, and triiodothyronine (T3) levels. Conclusion The findings indicate that Aplex and Venera have negative impacts on crucial biochemical and physiological indicators, particularly liver and kidney functioning.

Ammonia Scavenger Restores Liver and Muscle Injury in a Mouse Model of Non-alcoholic Steatohepatitis With Sarcopenic Obesity.

Recent studies have revealed that sarcopenia is closely associated with obesity and non-alcoholic steatohepatitis (NASH). However, few attempted to explore the cause-and-effect relationship between sarcopenic obesity and NASH. In this study, we investigated muscular alterations in a rodent NASH model to elucidate their intrinsic relations and explore the potential therapeutic target. Forty-six 8-week-old and twenty 42-week-old male C57BL/6 mice (defined as young and middle-aged mice, respectively) were fed with a high-fat diet (HFD) for 12 or 20 weeks. A subset of young mice was subjected to ammonia lowering treatment by L-ornithine L-aspartate (LOLA). We examined body composition and muscle strength by nuclear magnetic resonance and grip strength meter, respectively. At the end of the 12th week, all HFD-fed mice developed typical steatohepatitis. Meanwhile, sarcopenia occurred in HFD-fed middle-aged mice, whereas young mice only demonstrated decreased grip strength. Until the end of week 20, young mice in the HFD group exhibited significant sarcopenia and obesity phenotypes, including decreased lean body mass and grip strength, and increased body fat mass and percentage body fat. Additionally, plasma ammonia level was markedly increased in HFD-fed mice of both ages at week 20. Plasma ammonia level was negatively associated with muscle strength and myofiber diameter in young mice. LOLA can significantly reduce plasma levels of ammonia, alanine aminotransaminase, aspartate aminotransaminase, and cholesterol in mice fed an HFD. Hepatic infiltration of inflammatory cells and collagen deposition area were significantly decreased in HFD group by LOLA treatment. Meanwhile, LOLA significantly increased lean body mass, grip strength, and average muscle fiber diameter of HFD-fed mice. These findings suggest that the occurrence of NASH precedes sarcopenia in HFD mice, and the steatohepatitis-related hyperammonemia might contribute to the pathogenesis of sarcopenia. LOLA might be an effective drug for both steatohepatitis and sarcopenic obesity.

KEYNOTE-365 cohorts E and F: Phase 1b/2 study of pembrolizumab + lenvatinib combination therapy in patients with adenocarcinoma metastatic castration-resistant prostate cancer (mCRPC) or treatment-emergent neuroendocrine mCRPC (t-NE).

TPS215 Background: Standard of care for noncurative adenocarcinoma mCRPC is docetaxel or the next-generation hormonal agents (NHAs) abiraterone and enzalutamide. However, approximately 20% of patients develop t-NE after treatment for adenocarcinoma mCRPC; t-NE is associated with shorter survival, and it has no standard of care beyond combination platinum chemotherapy. The vascular endothelial growth factor (VEGF)/fibroblast growth factor receptor (FGFR) inhibitor lenvatinib inhibits proliferation and angiogenesis in preclinical models of adenocarcinoma prostate cancer. The phase 2 KEYNOTE-199 trial showed some antitumor activity with pembrolizumab monotherapy in docetaxel-pretreated patients with adenocarcinoma mCRPC. VEGF/FGFR inhibition combined with PD-1 inhibition may have enhanced benefit in mCRPC, for adenocarcinoma and possibly as a new treatment option for t-NE. Methods: KEYNOTE-365 (NCT02861573) is a nonrandomized, open-label, multicohort, phase 1b/2 trial designed to evaluate different pembrolizumab combination therapies in several patient populations with mCRPC. Cohort E will enroll patients with confirmed adenocarcinoma of the prostate without small cell histology, per investigator. Cohort F will enroll patients with t-NE (≥1% neuroendocrine cells in a recent biopsy specimen confirmed by central histology review). Each cohort will include patients who previously received docetaxel treatment for mCRPC. Prior treatment with ≤2 NHAs (for hormone-sensitive metastatic prostate cancer [mHSPC] or mCRPC) and 1 other chemotherapy for mCRPC is permitted. Additionally, enrollment in cohort F requires prostate cancer progression within 6 months of starting an NHA (for mHSPC or mCRPC) and within &lt; 6 cycles of docetaxel for mCRPC. Each cohort will enroll 40-100 patients with Eastern Cooperative Oncology Group performance status score of 0 or 1. Both cohorts will receive pembrolizumab 200 mg IV every 3 weeks + oral lenvatinib 20 mg once daily until disease progression, withdrawal of consent, prespecified alanine aminotransaminase or aspartate aminotransaminase level increase, or other discontinuation event. Primary end points are safety and tolerability, prostate-specific antigen (PSA) response rate, and objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR). Secondary end points include time to PSA progression; ORR and radiographic progression-free survival per Prostate Cancer Working Group 3 (PCWG3)–modified RECIST v1.1 by BICR; duration of response and disease control rate per RECIST v1.1 and PCWG3-modified RECIST v1.1 by BICR; and overall survival. These cohorts of KEYNOTE-365 are enrolling in Australia, Germany, New Zealand, Spain, and the United States. Clinical trial information: NCT02861573.

Screening and functional evaluation of the glucose-lowering active compounds of total saponins of Baibiandou (Lablab Semen Album)

ObjectiveTo screen for α-glucosidase inhibitor active compounds in the total saponins of Baibiandou (Lablab Semen Album) based on UHPLC-Q-Exactive Orbitrap MS technology and to evaluate its hypoglycemic activity in vivo. MethodsAcarbose was used as the positive control, and the median inhibitory concentration (IC50) was used as the evaluation index of α-glucosidase inhibitory activity to establish an in vitro α-glucosidase inhibition model. Further, UHPLC-Q-Exactive Orbitrap MS technology was used to screen and identify the active compounds of α-glucosidase inhibitors in the total saponins of Baibiandou (Lablab Semen Album) in order to further verify the activity of the main active monomer and to perform homologous modeling and molecular docking of yeast-derived α-glucosidase and human-derived α-glucosidase, while the hypoglycemic activity was evaluated in diabetic mice. ResultsThis study successfully identified 15 compounds with potential α-glucosidase inhibitory activity, including Chikusetsusaponin IVa, from the total saponins of Baibiandou (Lablab Semen Album). Simultaneously, we verified the activity of the main active monomer Chikusetsusaponin IVa, and showed that it has strong α-glucosidase inhibitory activity. The α-glucosidase inhibitory concentration IC50 was (565.2 ± 1.026) μg/mL, and the IC50 of acarbose, which was lower than the positive control, was (706.6 ± 1.058) μg/mL. The docking energies of Chikusetsusaponin IVa were – 6.1 and – 7.7 kcal/mol with yeast-derived α-glucosidase and human-derived α-glucosidase molecules, respectively. Both showed strong binding activity, and the levels of alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), UREA, Creatinine (CREA), and cholesterol (CHO) were significantly decreased by Chikusetsusaponin IVa (P < 0.05). In addition, it could repair damaged liver and pancreas cells of diabetic mice to some extent. ConclusionThis study provides a basis for screening α-glucosidase inhibitors and structural modifications of the total saponins of Baibiandou (Lablab Semen Album).

Amelioration of growth performance, physio-metabolic responses, and antioxidant defense system in rainbow trout, Oncorhynchus mykiss, using dietary dandelion, Taraxacum officinale, flower extract

In our study, the dietary effect of dandelion flower (DF) extract on growth performance, hemto-biochemical parameters, and transcriptomic responses of growth and antioxidant genes in rainbow trout were investigated. Accordingly, three hundred fingerlings were randomly stocked into 15 tanks and fed with different levels of DF extract (0 [control], 1, 2, 3, and 4 g/kg) for 8 weeks. The results showed the weight gain was significantly increased in 3 g/kg DF extract-supplemented group. The feed conversion ratio was significantly decreased in 3 and 4 g/kg DF extract treatments compared to the control group. The highest number of red blood cells and hematocrit level were observed in 3 g/kg DF extract treatment compared to 1 g/kg DF extract and the control group. A significant rise in the serum high-density lipoprotein, glutathione peroxidase (GPx), and catalase (CAT) was obtained in 3 g/kg DF extract. However, the levels of serum alanine and aspartate amino transaminase, and glucose were remarkably decreased at 3 g/kg DF added-group. The intestinal protease activity was significantly enhanced in the fish fed 3 g/kg DF extract compared to others. The body crude protein was also remarkably increased in the fish fed 3 g/kg DF extract. The transcriptomic responses of growth hormone, insulin-like growth factor-1, and ghrelin genes were notably up-regulated in the treated fish, especially in 3 g/kg DF extract. However, the expression of antioxidant-related genes (SOD, CAT, and GPx) was significantly decreased in DF extract-added groups. Overall, the optimal inclusion of DF extract in rainbow trout diet was ranged from 2.83 to 3.13 g/kg and 2.59 to 2.75 g/kg to improve growth performance and antioxidant status, respectively.

A Review on the Medicinal and Pharmacological Properties of Traditional Ethnomedicinal Plant Sonapatha, Oroxylum indicum

Oroxylum indicum, Sonapatha is traditionally used to treat asthma, biliousness, bronchitis, diarrhea, dysentery, fevers, vomiting, inflammation, leukoderma, skin diseases, rheumatoid arthritis, wound injury, and deworm intestine. This review has been written by collecting the relevant information from published material on various ethnomedicinal and pharmacological aspects of Sonapatha by making an internet, PubMed, SciFinder, Science direct, and Google Scholar search. Various experimental studies have shown that Sonapatha scavenges different free radicals and possesses alkaloids, flavonoids, cardio glycosides, tannins, sterols, phenols, saponins, and other phytochemicals. Numerous active principles including oroxylin A, chrysin, scutellarin, baicalein, and many more have been isolated from the different parts of Sonapatha. Sonapatha acts against microbial infection, cancer, hepatic, gastrointestinal, cardiac, and diabetic disorders. It is useful in the treatment of obesity and wound healing in in vitro and in vivo preclinical models. Sonapatha elevates glutathione, glutathione-s-transferase, glutathione peroxidase, catalase, and superoxide dismutase levels and reduces aspartate transaminase alanine aminotransaminase, alkaline phosphatase, lactate dehydrogenase, and lipid peroxidation levels in various tissues. Sonapatha activates the expression of p53, pRb, Fas, FasL, IL-12, and caspases and inhibited nuclear factor kappa (NF-κB), cyclooxygenase (COX-2), tumor necrosis factor (TNFα), interleukin (IL6), P38 activated mitogen-activated protein kinases (MAPK), fatty acid synthetase (FAS), sterol regulatory element-binding proteins 1c (SREBP-1c), proliferator-activated receptor γ2 (PPARγ2), glucose transporter (GLUT4), leptin, and HPV18 oncoproteins E6 and E7 at the molecular level, which may be responsible for its medicinal properties. The phytoconstituents of Sonapatha including oroxylin A, chrysin, and baicalein inhibit the replication of SARS-CoV-2 (COVID-19) in in vitro and in vivo experimental models, indicating its potential to contain COVID-19 infection in humans. The experimental studies in various preclinical models validate the use of Sonapatha in ethnomedicine and Ayurveda.

Double-lobectomy in a steatotic liver transplantation rat model.

Establishing a steatotic liver transplantation animal model can be a challenging process, which requires complex microsurgical technologies. The present study established a novel rat model of stable steatotic liver transplantation for marginal liver graft research, which notably minimized the number of animals used for the experiment. Briefly, male Sprague-Dawley rats (n=90) were fed with a high-fat diet (HFD; 60%, kJ) or standard chow diet (SCD) for 8 weeks. The liver enzymes and lipid levels were assessed every week, and the degree of steatosis was determined via hematoxylin and eosin and Oil Red O staining. The results demonstrated that there were no significant differences in alanine aminotransaminase and aspartate aminotransferase levels between the SCD and HFD groups (P>0.05), whereas the level of plasma triglyceride (TG) increased by 1.76-fold in the HFD group at week 2, and progressively decreased to baseline levels by week 8. Significantly higher levels of TG were observed in the HFD group compared with the SCD group at week 2 (P<0.05). In addition, the levels of plasma glucose (P<0.05), portal insulin (P<0.05) and content of liver lipid (P<0.01) increased in the HFD group compared with the SCD group. After 6 weeks, the liver steatosis was successfully formed and stable. Consequently, a rat liver developed hepatic macrovesicular steatosis >60%, which was subsequently used for transplantation after double-lobectomy. Post-transplantation survival rates in the HFD and SCD groups were as follows: Week 1, 80 vs. 100% and 1 month, 20 vs. 100%. A total of 20 rats were not sacrificed by performing double-lobectomy for biopsy. Taken together, the results of the present study suggest that rat liver double-lobectomy may be safely applied in steatotic liver transplantation without the need to sacrifice a large number of animals.

Protective Effect of Alpha-Lipoic Acid against Liver Damage Induced by Cigarette Smoke: An in vivo Study.

Background:Long-term cigarette smoking damages the liver tissue. Alpha-lipoic acid (ALA) is used as a therapeutic agent in a number of conditions and is known to have ameliorative effects against oxidative stress in the liver.Objective:To investigate the ameliorative effects of ALA on cigarette smoke (CS)-induced oxidative liver damage by examining histopathological, immunohistopathological changes and biochemical parameters in an animal model.Materials and Methods:Twenty-eight female Sprague–Dawley rats were randomly divided into three groups. In the control group (n = 8), rats were exposed to fresh air twice a day and given 0.1 ml of saline by gavage once a day for 8 weeks. In the smoking group (n = 10), rats were exposed to CS for 1 h in the morning and afternoon and given 0.1 ml of saline by gavage once a day for 8 weeks. In the smoking + ALA group (n = 10), CS exposure was same as the smoking group in addition to 100 mg/kg of ALA per day for 8 weeks through gavage. Oxidative damage in the liver tissue was determined by evaluating malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD) levels. Aspartate aminotransferase (AST), alanine aminotransaminase (ALT), alkaline phosphatase (ALP), direct bilirubin and total bilirubin levels were measured in the blood. Histopathological and immunohistochemical examinations were performed.Results:MDA (P = 0.011), AST (P = 0.018) and total bilirubin levels (P < 0.001) were increased, while CAT activity (P = 0.009) and the efficiency of SOD (P = 0.010) were decreased in the smoking group compared with the control group. CAT activity was increased (P = 0.017) and AST (P = 0.018) and total bilirubin levels (P < 0.001) were decreased in ALA-treated group compared with the smoking group. We observed vascular dilatation and hemorrhagic areas in the smoking group. TNF-α expression was increased in the smoking group compared with the control group. However, TNF-α expression was high in some preparations in the ALA-treated group.Conclusions:ALA can enhance antioxidant activity, but studies with different doses of ALA are required to determine the extent of its hepatoprotective effect.

Lactobacillus plantarum KSFY06 Prevents Inflammatory Response and Oxidative Stress in Acute Liver Injury Induced by D-Gal/LPS in Mice

AimThe purpose of this study is to investigate the preventive effect of Lactobacillus plantarum KSFY06 (LP-KSFY06) on D-galactose/lipopolysaccharide (D-Gal/LPS)-induced acute liver injury (ALI) in mice.MethodsWe evaluated the antioxidant capacity of LP-KSFY06 in vitro, detailed the effects of LP-KSFY06 on the organ index, liver function index, biochemical index, cytokines, and related genes, and noted the accompanying pathological changes.ResultsThe results clearly showed that LP-KSFY06 can remove 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzthiazoline −6-sulphonic acid) diammonium salt (ABTS) free radicals in vitro. The analysis of the organ index and pathology demonstrated that LP-KSFY06 significantly prevented ALI. Biochemical and molecular biological analysis showed that LP-KSFY06 prevented a decrease in the antioxidant-related levels of superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), catalase (CAT), and total antioxidant capacity (T-AOC), and also prevented an increase in aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) levels. LP-KSFY06 upregulated the anti-inflammatory factor interleukin (IL)-10 and downregulated the pro-inflammatory factors IL-6, IL-1β, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). These oxidative and inflammatory indicators were consistent with the results of gene detections. Furthermore, we determined that LP-KSFY06 downregulated Keap1, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), IL-18, and mitogen-activated protein kinase 14 (MAPK14 or p38), upregulated Nrf2, heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase [quinone] 1 (NQO1), B-cell inhibitor-α (IκB-α), and thioredoxin (Trx) mRNA expression. These may be related to the regulation of the Kelch-like ECH-associated protein-1 (Keap1)-nuclear factor-erythroid-2-related factor (Nrf2)/antioxidant response element (ARE) and NLRP3/NF-κB pathways.ConclusionLP-KSFY06 is an effective multifunctional Lactobacillus with strong anti-oxidant and anti-inflammatory ability that can prevent D-gal/LPS-induced ALI in mice and assist in maintaining health.

Comparative evaluation of graded levels of untreated and cellulase and pectinase hydrolyzed corncob based diets on performance, carcass yield, haematological and biochemical parameters of broiler chickens

This study was conducted to compare the effects of feeding graded levels of untreated and cellulase and pectinase hydrolyzed corncob based diets on growth, nutrient digestibility, carcass yield, haematological and biochemical parameters of broiler chickens. Three hundred and fifteen day-old broiler chicks with an average initial body weight of 60g were used for the study. Seven dietary treatments were formulated such that Diet 1 was a control. Diets 2, 3 and 4 contained 5%, 10%, and 15% levels of untreated corncob, while diets 5, 6 and 7 contained cellulase and pectinase hydrolyzed corncob at 5%, 10% and 15% levels respectively. The birds were randomly distributed into seven treatment groups in three replicates and each replicate had fifteen birds. Crushed corncobs were pretreated with NaOH to remove the lignin contents and later subjected to locally produced cellulase and pectinase enzymes for the degradation of non-starch polysaccharides (NSPs) for five days. Proximate analyses of untreated corncobs, cellulase and pectinase hydrolyzed corncob, standard diet, diets containing untreated corncobs and diets containing cellulase and pectinase treated corncobs were carried out to determine the nutrient composition of the ingredients and feeds. Data obtained from Growth performance, nutrient digestibility, haematological and serum biochemical profile as well as carcass yield were determined in a 2x4 factorial arrangement. Feeding regime was twice daily for all the treatment groups while diets and water were supplied to birds ad libitum. The results showed that at the end of week eight when the experiment was terminated, the broilers placed on untreated corncob diets consumed higher quantities (2497.28 g) of feed than birds placed on enzyme treated diets (2142.94 g) and conversely recorded lower performance indices in all parameters measured. The result also showed that as the levels of untreated corncob diets increased, the final body weight of birds (1450.00 g) significantly (P&lt;0.05) reduced when compared to 2385.33g obtained for enzyme treated birds. The result equally showed that broilers fed hydrolyzed corncob diets had significantly higher (P&lt;0.05) and better performance in terms of feed conversion efficiency (0.67 as compared to 0.50) in the untreated birds, protein efficiency ratio (4.17 as compared to 1.69) in the untreated birds, feed conversion ratio (1.21 as compared to 2.70) in the untreated birds, nutrient digestibility, final body weight, dressed carcass percentage (80.22 as compared to 73.93%) in the untreated birds and carcass cuts when compared to broilers fed untreated corncob diets. Enzyme treated corncob diets significantly (P&lt; 0.05) lowered the blood cholesterol levels (1.85 g/dL as compared to 2.15 g/dL) in the untreated birds and also improved other haematological indices measured in the birds compared to the control broilers. Generally, broilers fed enzyme hydrolyzed corncob diets performed better with birds fed 15.00% enzyme treated corncob diets having the highest and the best performance record which could be attributed to better utilization of nutrients since the enzymes have hydrolyzed the nutrient releasing monomers and hence are better metabolized. It is concluded that feeding broilers with enzyme hydrolyzed corn cob at the levels 5 to15.0 % improved performance and carcass values. In addition, it elevated 99 albumin, globulin, total protein, Aspartate amino transaminase (AST) and Alanine amino transaminase (ALT) levels in the blood.